Clinical Trials



The trials are divided into two broad categories:

Studies of new treatments

These studies test the effectiveness of experimental treatments, new combinations of drugs or new approaches to surgery, radiotherapy, etc.

Preventive studies

As its name indicates, a preventive study research how to prevent disease in people who have never contracted the disease or how to prevent a disease breaks out again. This type of study may use drugs, vitamins or vaccines.

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The launch of a clinical trial can not be conducted without a prior phase of experimentation in vitro or animal, also called preclinical phase. The experimental treatment the most promising laboratory will be selected to establish the corresponding therapeutic trial. A clinical trial is conducted in four distinct phases, each phase having a specific goal:

Phase I - This is the first drug administration in humans. This phase involves the evaluation of the tolerance of the compound and possible side effects in a small group of subjects (10 to 80 participants). This phase also allows to study the distribution and elimination of the compound in the body.

Phase II - The goal is to determine the efficacy and optimal dose of treatment while controlling the associated side effects. Treatment at this stage is given to a larger group of subjects (100-300 people).

Phase III - This phase corresponds to the study of the effectiveness of treatment on a larger scale. It occurs at least two groups of subjects simultaneously: one group receiving the test product and a control group receiving a placebo or standard treatment. Special case in diseases where the patient's life is at stake, all participants are treated with the active product. The composition of the groups should be similar in terms of age, sex, height, weight, severity and stage of the disease to allow a fair comparison. Subjects are subjected to medical examinations to measure the parameters defined by the trial protocol and verify the effectiveness of treatment. Side effects (if they exist) continue to be identified and treated if the doctor deems it necessary. At this stage, the study groups consist of 1 000-3 000. When the results show that the treatment is beneficial, permission marketing is issued by the health authorities (in France AFSSAPS). Phase III trials are usually randomized, blinded, multicenter made.

Phase IV - It represents the long-term monitoring of treatment after marketing. Its purpose is to document additional benefits detect rare side effects and late complications if any. Rare diseases: Due to the rarity of the diseases, the number of patients in different phases is reduced. Important: the average duration of a therapeutic trial is variable depending on the type of study. The average time between the start of the study and the marketing of the product used for the treatment is usually 10 years.

A legal system (in France, Huriet) is in place to inform and protect participants in a clinical trial. The protocol of the clinical trial must necessarily be subject to the approval of a committee for the protection of people (in France, CCPRB). This committee checks the value of the study, the risks / benefits expected by patients, compliance methodologies and the purchase of insurance to compensate study participants for damage.

The physician responsible for the test has an obligation to inform participants and warn of potential risks. If the subject decides to participate in the study, he signed before the start of the test letter of consent attesting to the understanding, commitment and agreement to participate in the trial. The participation of a subject in a therapeutic trial is voluntary. Legally, nothing can be done without the patient's consent. In addition, at any time, an individual may withdraw from a clinical trial for no particular reason.

A therapeutic trial can be stopped prematurely if the results show that the treatment is extremely beneficial (so as not to deprive patients receiving placebo) or when it causes side effects too dangerous. Case of clinical trials for children and adolescents Children and adolescents can participate in a study without the signed consent of their parents or legal guardian, or without their opinion, they are able to give. A negative opinion of the child or young person is refusing to consent even if the parents have a favorable opinion.

  • Why participate in a clinical trial?

Participants in a clinical trial can play an active role in their own health benefit of new treatments before they are marketed possible and help the community by investing in medical research.

  • Who can participate in a clinical trial?

Chaque essai est accompagné d'un protocole définissant les types de sujets pouvant (critères d'inclusion) ou ne pouvant pas y participer (critères d'exclusion). Ces critères sont basés sur des facteurs comme l'âge, le sexe, le type et l'avancement de la maladie, les traitements antérieurs et autres conditions médicales afin d'identifier une population de sujets homogène pouvant tolérer le traitement expérimental.

  • Who funds the trials?

The trials are extremely expensive. They may be funded by different organizations or individuals: doctors, hospitals, foundations, pharmaceutical companies and research institutions (France, INSERM, for example). ELA Foundation has decided to become more involved in clinical trials. In 2007, she will be the sponsor of a clinical trial on Canavan disease.

  • Questions to consider before participating in a clinical trial:

What is the purpose of the study? Who will participate in the study? What is the treatment used? This treatment he been tested? What is the duration of the test? Hospitalization is necessary? Who will take care of my health? My doctor? Why doctors believe that treatment will be effective? What are the benefits / risks of this treatment compared to my current treatment? What medical tests will be performed? What is their frequency and duration? Where will the examinations and consultations? What to do if a problem arises? How this study will impact my daily life? Who will bear the costs of the study? My expenses this study be supported? How do I know if the treatment is effective? Me the results be communicated? What type of long-term monitoring is planned? The patient may he continue treatment at the end of the trial? Participate in a clinical trial is an important personal decision. Before making this decision, it is recommended to read the documents submitted, request more information, talk to the doctor responsible for the testing, seek the advice of your doctor (if different from that in load test) to see family and friends and take time to reflect.

Several clinical trials for adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease and Pelizaeus-Merzbacher disease are being developed.

Find out here

Clinical trials for adrenoleukodystrophy



Find the latest information related to clinical trials for adrenoleukodystrophy and adrenomyeloneuropathy in this section.

Status

  • Authorized in France and Spain
  • On-going patient recruitment in France and Spain
  • Awaiting authorization in Germany

Drug: MD1003 (biotin)
Objectives

  • To show clinical efficacy of the MD1003 treatment in AMN compared to placebo
  • To evaluate the safety of the treatment

Duration of the trial: 2 years
Start date: November 2014
Estimated end of the trial: April 2017

Principal investigator: Pr Patrick Aubourg, Bicetre hospital, Le Kremlin-Bicetre, France
Investigators

  • Pr Patrick Aubourg, Bicetre hospital, Le Kremlin-Bicetre, France
  • Dr Yann Nadjar, Pitié-Salpêtrière hospital, Paris, France
  • Dr Aurora Pujol, IDIBELL, Duran i Reinals hospital, L’Hospitalet de Llobregat, Spain
  • Dr Carlos Casasnoves, IDIBELL, Duran i Reinals hospital, L’Hospitalet de Llobregat, Spain
  • Pr Wolfgang Köhler, Hubertusburg hosital, Wemsdorf, Germany

Locations

  • Bicetre hospital, Le Kremlin-Bicetre, France
  • Pitié-Salpêtrière hospital, Paris, France
  • Duran i Reinals hospital, L’Hospitalet de Llobregat, Spain
  • Hubertusburg hospital, Wermsdorf, Germany

Sponsor: MedDay Pharmaceuticals, France - http://medday-pharma.com/
Funding: ELA - 800.000 euros
Reference : EudraCT 2014-000698-38
Patients
60 AMN men divided into 2 groups the first year of the treatment as follows:

  • 20 patients treated with a placebo
  • 40 patients treated with the MD1003 drug

During the second year of the trial, all the patients will receive the MD1003 drug.

Experimental treatment
Oral daily intake of MD1003 capsules at a dose of 300 mg or of placebo

Inclusion criteria

  • 18 to 60 years old men
  • Confirmed ABCD1 gene mutation
  • Increased very long chain fatty acids in plasma
  • Clinical signs of AMN with walking impairment
  • Normal cerebral MRI or MRI showing abnormalities of AMN patients without cerebral involvement
  • Corticoid treatment if adrenal insufficiency

Exclusion criteria

  • IMRI showing abnormalities of AMN patients with cerebral involvement
  • Other progressive neurological disease than AMN
  • Unable to perform walking and balance tests
  • Patients with liver impairment, renal or cardiovascular disease or evolutive cancer
  • Intake of drugs for AMN including fampridine if initiated less than a month before inclusion
  • MRI contraindications
  • Participation to another clinical trial for ALD

Outcome measures
Principal outcome measure: Mean change observed during the 2 Minutes walking test prior and after the 12 months treatment.

Secondary outcome measures

  • TW25FW walking test measuring the time to walk 25 feet
  • Time to stand up and go
  • Euroqol ED-5D quality of life questionnaire
  • Qualiveen questionnaire on urinary function
  • Safety assessment of elevated dose of biotin

Exploratories studies will also be conducted in some centers like MRIs, nerve velocity conduction and muscular strength.

Additional information

Contacts
France
email : jf.dhainaut@ela-fondation.com

Spain
Telephone : +34 932 607 137
Fax: +34 932 607 414
email : contact@medday-pharma.com

Source : https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000698-38/ES

Status: Authorized; patient recruitment active (Boston site)
Drug: Lentiviral vector Lenti-D carrying the normal human ABCD1 gene
Objective: To evaluate the safety and efficacy of the treatment in childhood cerebral ALD

Start date of the study: August 2013
Estimated end of the trial: August 2018

Director of the study: Dr. Asif Paker, bluebird bio, Inc.
Principal investigators

  • Dr. David Williams, Boston Children's Hospital, Boston, MA, USA
  • Dr. Christine Duncan, Children's Hospital, Boston, MA, USA
  • Dr. Florian Eichler, Massachusetts General Hospital, Boston, MA, USA

Locations:

  • Boston Children Hospital / Massachussetts General Hospital, Boston, MA, USA
  • University of California, Los Angeles, California, USA
  • University of Minnesota, Minneapolis, Minnesota, USA

Funding: bluebird bio

Reference : ALD-102 study, Starbeam study, NCT01896102

Patients
Fifteen children suffering from the cerebral form of ALD at a pre-symptomatic stage

Experimental protocol

  • Collection of bone marrow stem cells from the patient blood and isolation of the CD34+ stem cells
  • Transfer of the gene into the CD34+ stem cells using the viral vector.
  • Myeloablative conditioning of the patient (destruction of the bone marrow).
  • Reinfusion of the corrected cells in the patient (autotransplant).

Inclusion criteria

  • Age: Up to 15 years old
  • Gender: Male
  • Active childhood cerebral adrenoleukodystrophy
  • Neurological function score ≤ 1

Exclusion criteria

  • Receipt of an allogeneic transplant or gene therapy.
  • Availability of a willing 10/10 matched sibling donor.
  • Use of statins, Lorenzo's oil or diets aiming at lowering very long chain fatty acids. Note : subjects must discontinue use of these medications at time of consent.
  • Impossibility to perform MRI studies.
  • Hematological, hepatic, renal, pulmonary or cardiac compromise.
  • Infections and other conditions.

Patient follow-up
Patients will be followed-up several years after their gene therapy treatment.

Additional information

  • Other centers will be opened in the future in the United States and in Europe. When new centers will be authorized, we will update the section «  Clinical trials » of our website.

 

Contacts

  • Tara O'Meara, bluebird bio, Inc. – Telephone : +1 617-797-2555, e-mail : clinicaltrials@bluebirdbio.com
    Colleen Dansereau, Boston Children's Hospital/Massachusetts General Hospital – Telephone : +1 617-919-7008, e-mail : Colleen.Dansereau@childrens.harvard.edu
  • Dr Ami J Shah - University of California, Los Angeles, California, USA - Telephone : +1 310-825-6708, e-mail: AJShah@mednet.ucla.edu
  • Dayna Terrazas  - University of California, Los Angeles, California, USA - Telephone : +1 310-825-6708, e-mail : drterrazas@mednet.ucla.edu
  • Dr Paul Orchard - University of Minnesota, Minneapolis, Minnesota, USA - Telephone : +1 612-626-2313, e-mail : orcha001@umn.edu
  • Patty Kleinke - University of Minnesota, Minneapolis, Minnesota, USA - Telephone :  +1 612-273-0857, e-mail: pkleink1@fairview.org

Source: http://clinicaltrials.gov/ct2/show/NCT01896102
http://www.starbeamstudy.com

Status: Authorized; Not yet open for recruitment
Objective: To evaluate the safety and efficacy of allogenic hematopoietic stem cell transplantation in patients with childhood cerebral ALD aged 17 or younger.

Start date of the study: November 2014
Estimated end of the trial: November 2018

Director of the study: Dr. Asif Paker, bluebird bio, Inc.
Funding: bluebird bio

Reference : ALD-103 study, NCT02204904

Patients
35 boys aged 17 or younger receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of Childhood Cerebral Adrenoleukodystrophy prospectively or partially prospective/retrospective.

Primary outcome measures

  • Mortality
  • Incidence of successful of engraftment
  • Kinetics of engraftment
  • Frequency and severity of adverse events

Inclusion criteria

  • Be male and aged 17 years and younger (i.e., <18 years of age) at the time of parental/guardian consent and, where appropriate, subject assent.
  • Have a confirmed diagnosis of Childhood Cerebral ALD
  • Be scheduled for allo-HSCT evaluation/procedure at a study site or have received allo-HSCT within a maximum of 12 months before study site activation.

Exclusion criteria

  • Previous treatment with a Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy product
  • Received allo-HSCT earlier than 12 months before study site activation

Contact

Source: http://clinicaltrials.gov/show/NCT02204904

Status: Active - Recruiting patients
Objective: To evaluate abnormalities of the brain and spinal cord by MRI in order to understand the mechanisms leading to the disability of women with adrenomyeloneuropathy and the effect of physical exercise.

Investigator: Kathleen Zackowski, Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MA, USA

Start date: May 2012
Location: Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MA, USA
Duration: 25 months
Funding: ELA
Reference: NCT01594853

Patients
30 women with adrenomyeloneuropathy

SourceClinicaltrials.gov

Status: Closed
Objective: To test the efficacy of a cocktail of antioxidants in AMN patients
Drugs: Cocktail of 2 antioxidants (Vitamin E, Lipoic Acid) + N-acetylcysteine (expectorant)

Principal investigators
Dr. Aurora Pujol, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Dr. Carlos Casasnovas, Department of Neurology, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain

Start date: September 2011
Location: Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain
Duration: 26 months
Funding: Spanish Ministry of Health, Hesperia Foundation, ELA.
Reference: NCT01495260

Patients
20 AMN men with locomotor impairment
Symptomatic female carriers

Treatment
Daily intake of the 3 drugs

Outcome measures

  • Oxidative stress markers
  • Clinical assessments at the beginning and end of the study

SourceClinicaltrials.gov

Preliminary results of the trial (page 3)

Until now, treatment for ALD relied on bone marrow transplantation, an limited approach given the scarcity of donors and the risk of serious complications. In this new approach, clinicians chose autotransplantation combined with Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy. Stem cells from the patient bone marrow were collected and corrected in the laboratory before being reinfused to the patient. Some of these cells will naturally head to the brain of the patient where they could have a corrective effect.

Technological innovation: a viral vector derived from an inactivated and modified AIDS virus was used to introduce the correct gene in bone marrow stem cells. A discovery that opens up treatment perspectives  for other types of leukodystrophy and that will benefit other more common diseases (sickle cell anemia, beta-thalassemia, multiple immunodeficiencies, hemophilia, Parkinson's ...).

Status: Closed
Drug: Lentiviral vector carrying the normal human ABCD1 gene
Objective: Evaluation of the safety and efficacy of the treatment

Principal investigators
Patrick Aubourg, Bicêtre Hospital, Paris, France
Alain Fisher, Necker Hospital, Paris, France
Marina Cavazzana-Calvo, Necker Hospital, Paris, France

Start date: Fall 2006
Location: Bicêtre Hospital / Necker Hospital
Funding: ELA, Inserm, AP-HP, Paris Descartes University, AFM

Patients
4 children suffering from cerebral form of the disease at a presymptomatic stage without compatible bone marrow donors and with a progressive cerebral demyelination and adrenal insufficiency.

Experimental treatment in 4 phases

  • Collection of bone marrow stem cells from the patient blood and isolation of the stem cells
  • Transfer of the gene into the stem cells using the lentiviral vector
  • Myeloablative conditioning of the patient (destruction of the bone marrow)
  • Reinfusion of the corrected cells in the patient (autotransplant).

Patient follow-up

Patients will be followed for several years after their gene therapy treatment.

The results regarding the first two children treated were published in the prestigious scientific journal Science. After 24 to 30 months of patient follow-up , 10 to 15% of the patients’ blood cells still express the ALD protein that was previously undetectable. The normal ABCD1 gene was expressed by these cells four to five times more than the mutated gene. Also, 20 to 24 months after transplant, VLCFA that normally accumulate during the disease were reduced by 38% in the patients' plasma. From a neurological point of view, the cerebral demyelinating lesions in these two children progressed 14 to 16 months after transplant but have remained stable since then. In addition, the demyelinating lesion observed in the auditory pathway of one patient was reversed.

The arrest of progressive cerebral demyelination in these two children treated by gene therapy represents a clinical outcome comparable to that achieved by allogeneic bone marrow transplantation in ALD patients.

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Clinical trials for metachromatic leukodystrophy



Below is the up-to-date information regarding clinical trials for metachromatic leukodystrophy.

Status: Active; Recruitment of patients
Experimental drug: AAVrh10cuARSA viral vector
Objective: To evaluate the tolerance and efficacy of the treatment

Investigators
Pr. Patrick Aubourg, CHU Bicêtre Paris Sud and Inserm U986, Le Kremlin-Bicêtre, France
Dr. Caroline Sevin, CHU Bicêtre Paris Sud and Inserm U986, Le Kremlin-Bicêtre, France
Dr. Nathalie Cartier-Lacave, Inserm U986, Fontenay-aux-Roses, France
Pr. Michel Zerah, CHU Necker and Inserm U986, Paris, France
Dr. Thomas Roujeau, Hôpital Gui de Chauliac, Montpellier, France

Start date: March 2013
Location: Neuropediatric Department, Bicêtre Hospital Paris Sud, Le Kremlin-Bicêtre, France and Neurosurgery Department (Pr. M. Zerah), CHU Necker, Paris, France
Funding: ELA, PHRC, Inserm
Reference: NCT01801709

Patients
5 children with early onset forms of metachromatic leukodystrophy (MLD)

Treatment
The administration of the viral vector in the brain of the sick children will be performed by  neurosurgical procedure, under general anesthesia, through by 6 small holes (of 2 mm) in the skull, to achieve 12 simultaneous deposits of the drug inside the brain.

Inclusion criteria

  • Boys or girls with an early onset form of MLD.
  • Age between 6 months and 5 years, inclusive
  • Confirmed diagnostic of MLD

Exclusion criteria

  • Specific criteria linked to the form of MLD
  • If older  > 16 months at time of inclusion, inability to walk few steps alone OR inability to walk few steps with support on one side along with inability to stand up alone
  • Unable to perform  exams  during the trial (MRI, anesthesia, evoked potentials)
  • Any other significant medical condition
  • Participation to another therapeutic clinical trial for MLD

Source: ClinicalTrials.gov

As for the Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy trial in adrenoleukodystrophy, patients are grafted with their own stem cells from bone marrow prior corrected using a lentiviral vector.

Status: Ongoing - Recruitment of patients by invitation
Objective: Evaluation of the safety and efficacy of treatment
Medication: lentiviral vector with the normal human gene ARSA
Reference: NCT01560182

physicians responsible

  • Dr. Alessandra Biffi, Pediatrician at Pediatric Unit of Immunohematology and Bone Marrow Transplantation of HSR.
  • Dr. Maria Sessa, Neurologist in the Department of Neurology at HSR.
  • Dr Attilio Rovelli, Director, Center for Bone Marrow Transplantation in the Department of Pediatrics, San Gerardo Hospital, Monza.
  • Prof. Luigi Naldini, Director of HSR-TIGET
  • Professor Maria Grazia Roncarolo, Director Unit Pediatric Immunohematology and Bone Marrow Transplantation of HSR.

 

Start of the trial: March 2010
Estimated end of the trial: October 2022
Location: Pediatric Clinical Research Unit of HSR-TIGET & Unit Pediatric Immunohematology and Bone Marrow Transplantation of HSR, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy.
Sponsor: GlaxoSmithKline
Funding: Italian Telethon Foundation, ELA

patients
20 children with a diagnosis of MLD confirmed by determination of ARSA enzyme activity or by genetic analysis

Forms of the disease concerned:

  • children with late infantile form pre-symptomatic
  • children with early juvenile form pre-symptomatic or within 6 months after the onset of symptoms

  Experimental treatment in 4 phases

  • Removal of bone marrow from the patient and isolation of stem cells to treat;
  • Cell manipulation and gene transfer to cells with the lentiviral vector;
  • Myeloablative therapy the patient (Destruction of the bone marrow);
  • Reinjection engineered cells to the patient (autologous).

Source : ClinicalTrials.gov

Consultez les résultats intermédiaires de l'essai (pages 6-7)

This study is to provide every 2 weeks the normal ARSA enzyme in human cerebrospinal fluid of children with metachromatic leukodystrophy.

Status: Ongoing - Recruitment of patients ended

Type of study: Phase I / II multicenter, open, with ascending doses of drug

Medicine: HGT-1110, human ARSA enzyme formulation normal intrathecal injection.

Reference: NCT01510028

Objective: To determine the safety of doses ascendantes de HGT-1110 administered by intrathecal injection for 38 weeks in children with metachromatic leukodystrophy.

Area of trying

  • University Hospital of Copenhagen, Copenhagen, Denmark
  • Bicetre Hospital, Le Kremlin-Bicetre, France
  • Universitats-Kinderklinik, Tubingen, Baden-Wuerttemberg, Germany

Study Director: Dr. Eric Crombez, Shire Human Genetic Therapies, Inc..

Physicians responsible

  • Dr. Christine Dali, Department of Clinical Genetics, Juliane Marie Centre, University Hospital of Copenhagen, Copenhagen, Denmark christine.dali@rh.regionh.dk
  • Dr. Caroline Sevin, Department of Pediatric Neurology, Bicetre Hospital, Le Kremlin-Bicetre, France     caroline.sevin@inserm.fr
  • Dr. Joachim Riethmuller, Center for Pediatric Clinical Studies, Universitats-Kinderklinik, Tubingen, Baden-Wuerttemberg, Germany     joachim.riethmuller@med.uni-tuebingen.de

Beginning of the study in September 2012

Estimated study completion: March 2015

Sponsor: Shire Human Genetic Therapies, Inc.

Patients

Maximum 18 patients participating in the trial. All receive treatment HGT-1110. Boys and girls are eligible.

Inclusion criteria

  • Diagnosis of metachromatic leukodystrophy confirmed both by a deficiency of arylsulfatase A as measured by the test on white blood cells and urinary sulfatides high
  • The first symptoms of the disease at the age of 30 months or earlier.
  • Being ambulatory at the time of patient selection (ability to walk 10 steps with one hand held).
  • The patient must be less than 12 years old.
  • Present metachromatic leukodystrophy neurological signs at the time of patient selection.
  • The patient and his parents or guardians must satisfy the constraints of the clinical protocol.
  • Parents or legal guardians of the patient must sign a letter of consent before inclusion.

Exclusion criteria

  • History of bone marrow transplantation.
  • Known or suspected hypersensitivity to anesthesia or high risk for anesthesia in case of problems with respiratory or other medical problems.
  • Other medical problem or serious illness.
  • The patient is participating in another clinical trial within 30 days prior to consideration for inclusion in the study.
  • The patient is pregnant or breastfeeding.
  • The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:
    • The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
    • The patient's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator.
    • The patient has a known or suspected local or general infection.
    • The patient is at risk of abnormal bleeding due to a medical condition or therapy.
    • The patient has one or more spinal abnormalities that could complicate safe implantation or fixation.
    • The patient has a functioning CSF shunt device.
    • The patient has shown an intolerance to an implanted device

Experimental treatment (3 groups)

  • Group 1: 6 patients treated for 38 weeks with 10 mg of HGT-1110 every 2 weeks by intrathecal injection via a specific device.
  • Group 2: 6 patients treated for 38 weeks with 30 mg of HGT-1110 every 2 weeks by intrathecal injection via a specific device.
  • Group 3: 6 patients treated for 38 weeks with 100 mg of HGT-1110 every 2 weeks by intrathecal injection via a specific device.

Evaluation Criteria

Primary criteria: Safety of the administration of HGT-1110 intrathecal

Secondary endpoints

  • Effect of the administration of HGT-1110 intrathecally on motor function
  • Pharmacokinetic profile of HGT-1110 in serum after administration of a single dose or repeated doses
  • Concentrations of HGT-1110 in the cerebrospinal fluid before each intrathecal administration

Patients who participated in the study through week 40 can be invited to participate to the extension study (Referenced NCT01887938) which goal is to evaluate long-term safety and efficacy of intrathecal administration of HGT-1110 in patients with metachromatic leukodystrophy.

Source: ClinicalTrials.gov

Status: Ongoing - Recruitment of patients
Objective: To study the progression of cerebral MLD by new techniques and MRI abnormalities correlate with tests assessing motor and intellectual function of the patient.

Principal investigators

  • Professor Patrick Aubourg, Department of Pediatric Neurology, Bicêtre Hospital, Le Kremlin-Bicetre, France
  • Dr Caroline Sevin, Pediatric Neurology Department, Hôpital Bicêtre, Le Kremlin-Bicetre, France
  • Dr. Lucie Hertz-Pannier, Biomedical Research Unit, Neurospin, Gif-sur-Yvette, France
  • Dr Laurence Lecomte, Necker Hospital, Paris, France

Location : Bicêtre Hospital, Le Kremlin-Bicetre & Neurospin, Gif-sur-Yvette, France
Start date: September 2010
Duration of the study: 6 months for MLD patients; 12 months for controls
Funding: AP-HP, ELA
Reference: NCT01325025

Patients

  • 10 children between 1-6 years with a diagnosis of metachromatic leukodystrophy less than 18 months.
  • 25 controls

Experimental design
2 visits are scheduled:

  • Visit 1: MRI and evaluation of motor and cognitive functions
  • Visit 2 (6 months after visit 1 for MLD patients; 12 months after visit 1 for controls): MRI and evaluation of motor and cognitive functions

MRI
Its duration does not exceed 60 minutes. The child must be fasting at least 3 hours before the exam. To ensure the immobility of the child during the examination, a sedative, chloral hydrate, it is administered orally or rectally. After the examination, the child will remain supervised on site 1-2h before departure.

Source : ClinicalTrials.gov

Clinical Trials for Krabbe disease



Find the latest information related to clinical trials for Krabbe disease in this category.

labo5

On 27 September 2011, the European Commission has designated the drug "recombinant human galactocerebrosidase" (Galaczym) of ACE BioSciences A / S, a subsidiary of Zymenex Holding A / S as an orphan drug for the indication: Treatment of KrabbeCe disease drug is entered in the Community Register of Orphan Medicinal Products under number EU/3/11/911.

On 12 December 2011, Galaczym also obtained orphan drug designation by the U.S. Food and Drug Administration (FDA), Health Authority of North America.

Orphan designation is an initiative to encourage pharmaceutical companies to develop treatments for rare diseases. It is accompanied by incentives to promote research, development and
market designated medicinal product. It is in no way authorized therapeutic trial or marketing.

Krabbe disease (also known as globoid cell leukodystrophy) is an inherited disease due to lack of an enzyme called galactocerebrosidase is necessary for the degradation of certain fats such as galactosylceramide and psychosine.
The accumulation of these substances is responsible for the destruction of the myelin cells to cause lesions in the brain.

OFFICIAL PUBLICATIONS

Clinical trials for Pelizaeus-Merzbacher disease



Find the latest information related to clinical trials for Pelizaeus-Merzbacher disease in this category.

This is the first clinical trial with stem cells for treating a neurodegenerative disease resulting from a lack of myelin. Its aim is to test the safety and efficacy of transplantation of neural stem cells HuCNS-SC ® in pediatric patients with Pelizaeus-Merzbacher disease. These cells are derived neural precursors in the brain of fetuses that have the ability to produce oligodendrocytes, myelinating cells of the brain.

StemCells, Inc.., The biotechnology company that developed these cells, has completed a Phase I clinical trial in January 2009 when six patients with Batten disease, another rare disease, were treated similarly and reported positive results in terms of safety. The engraftment and long-term survival of cells in the brain were also found.

Status: Closed
Objective: To test the safety of transplanted cells and the effectiveness of the transplantation
Type of Test: Cell Therapy
Medicine: Human Neural Stem Cells
Reference: NCT01005004

Responsible physician
Dr. David Rowitch, chief of neonatology at Children's Hospital of the University of California at San Francisco and a member of the Scientific Board of the ELA Foundation.

Beginning of the test: 23/11/2009
Place: Department of Neonatology at Children's Hospital of the University of California, San Francisco
Funding: StemCells, Inc..

Patients
4 patients in the form conatale, the most severe form of the disease, participating in this trial. Children, only U.S. citizens or Canadians living in North America, had to meet the following inclusion criteria to participate in this clinical trial:

  • Boys with an age between 6 months and 5 years
  • Genetic tests confirming the PLP1 mutation
  • Decrease in cerebral white matter and brain volume by MRI
  • Clinical diagnosis of PMD conatale confirmed
  • Ability of the family to follow the protocol
  • Family's ability to understand the study and consent

Experimental treatment
Children:

  • received transplantation of neural stem cells by neurosurgery,
  • receive immunosuppressive therapy during the next nine months to prevent the rejection of transplanted stem cells,
  • followed intensively for one year to assess the safety and tolerability of the transplanted cells, the effects of surgery and immunosuppression but also to see if the children show signs of clinical improvement.

Various examinations will be used in this study including MRI to monitor the production of myelin, clinical examinations that will thoroughly evaluate neurological function and of the minutes from the parents.

Source: ClinicalTrials.gov

See the preliminary results of the test (pages 12-13)

Monitoring of patients
MRI scans of the brain will be made for an additional four years to monitor potential problems associated with these cells.
Part of this follow-up study: NCT01391637 / Source: ClinicalTrials.gov

Clinical trials for Zellweger spectrum disorders



In this section, you will find up-to-date information regarding clinical trials for Zellweger spectrum disorders, also known as fatty acids." >peroxisome biogenesis disorders, i.e.:

Status: Active ; Currently recruiting patients
Drug: Betaine (or trimethylglycine)
Objective: To test if betaine can recover fatty acids." >peroxisome biochemical functions in blood

Start date: March 2013
Estimated end of the study: June 2014
On-going data analysis

Principal investigator: Nancy Braveman, Montreal Children’s Hospital, Quebec, Canada
Location: Montreal Children’s Hospital, Quebec, Canada
Funding: McGill University Health Center, Orphan Europe
Reference: NCT01838941, RPGDN001

Patients
12 children with a peroxisome biogenesis disorder (Infantile Refsum disease or neonatal adrenoleukodystrophy) carrying the PEX1-Gly843Asp mutation.

Experimental protocol
During this pilot study, betaine will be given orally or through gastrostomy tube at the following doses:

  • For children weighting less than 30 kg : 6 g per day in 3 divided doses (2 g, 3 times daily)
  • For children weighting more than 30 kg : 12 g per day in 4 divided doses (3 g, 4 times daily)

Inclusion criteria

  • Boy or girl
  • Any age
  • Diagnosis of peroxisome biogenesis disorder confirmed
  • Clinical syndromes: Infantile Refsum disease or neonatal adrenoleukodystrophy
  • Mutation : PEX1-Gly843Asp

Exclusion criteria

  • Patients carrying mutations other than PEX1-Gly843Asp
  • Patient already treated with betaine

Testings

  1. Peroxisome biochemical functions as measured by:
    • plasma very long chain fatty acid profiles
    • red cell plasmalogen levels
    • plasma pipecolic acid levels
    • plasma bile acid profiles

2. Growth developmental status

Contacts

Nancy Braveman         Tel : +1 514 934 1934 (ext. 23404)          e-mail : nancy.braveman@mcgill.ca
Dan A. Chiche                Tel : +1 514 575 6958                                    e-mail : chiched@gmail.com

Source : http://clinicaltrials.gov/ct2/show/NCT01838941

Clinical trials addressing different leukodystrophies



Find the latest information related to clinical trials addressing different leukodystrophies in a single trial.

Status: Patient Recruitment
Drug: L-DOPA
Objective: To assay the effectiveness of L-DOPA in improving akinetic-rigid symptoms occurring in several leukodystrophies

Start date: July 2013
Estimated completion date: July 2014
On-going data analysis

Director of the study: Vincenzo Leuzzi, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome
Investigators:

  • Barbara Tavazzi, Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome
  • Giuseppe Lazzarino, Division of Biochemistry and Molecular Biology, Department of. Biology, Geology and Environmental Sciences, University of Catania
  • Claudia Carducci, Department of Experimental Medicine, Sapienza University of Rome
  • Andrea Celato, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome
  • Federica Rachele Danti, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome
  • Maria Teresa Giannini, Department of Pediatric Neurology and Psychiatry, Sapienza University of Rome

Location of the trial: Department of Pediatric Neurology and Psychiatry, Umberto I Hospital, Rome, Italy
Sponsor: Umberto I Hospital, Rome, Italy
Funding: ELA Italy (patient support)

Patients
This study was designed as a fully open trial. Due to disease heterogeneity and variability of motor and functions impairment it is not feasible to apply a standardized protocol. Patients have been sub-grouped according to the stage of the progression of their disease and the type of their prevalent motor dysfunction. An intra-patient comparison, before and after pharmacological therapy, have been used to assess clinical effectiveness. No placebo, gender or stricted age limits will be taken into account due to mentioned reasons.

Experimental protocol
Neurotransmitters dysfunction in white matter disorders is still a controversial matter but the efficacy of L-DOPA, as described in some case studies, reminds to a supposed biogenic amines defect. This protocol ground on previous, single-patient, description of the effectiveness of L-DOPA in treating some target symptoms occurring in several forms of leukodystrophies and leukoencephalopathies. For instance some white matter disorders affected patients develop, during the course of their disease, akinetic patterns together with hypomimia, rigidity, dizziness, dystonia, slowness of movements, tremor, speech and swallowing dysturbances, dysautonomia, hyporesponsiveness to social and nonsocial stimuli or neurobehavioural problems and with signs of dopaminergic impairment. This could be, in some ways, connected to a parkinsonian-like pediatric phenotype. The main target of the present protocol has been the assessment of the effect of L-DOPA/carbidopa in improving the central motor deficits affecting patients with leukodystrophy.

Time table of the trial
Time 0: patient recruitment

Time 1: clinical and biochemical assessment

  1. Assessment of biogenic amines in urine
  2. Clinical assessment tools:
  • Vineland Adaptive Behavior Scale
  • Gross Motor Function Classification System (GMFCS)
  • International Cooperative Ataxia Rating Scale (ICARS)
  • Dyskinesia Impairment Scale (DIS)
  • Standardized video recordings

3.    Treatment protocol: L-DOPA/carbidopa administered starting from a dosage of 1 mg/kg/day for fifteen days and 5 mg/kg/day for the following 30 days. Domperidone will be considered in preventing gastrointestinal disorders in some cases.

Time 3: At day 45 the patient was again assessed according to the same clinical protocol

Time 4: In case of not satisfactory or absent clinical effect the dosage will be increased up to 10 mg/kg/day for a further month and then patients again re-assessed at the end of this period according to identical clinical protocol.

Eligibility

Inclusion criteria

  • Patient affected by primary leukodystrophies or leukoencephalopathies
  • Presence of disabling akinetic-rigid symptoms, hypokinesia, bradykinesia, hypomimia, rigidity, rest tremor, dystonia etc.
  • Age > 2 years

Exclusion criteria

  • Severe clinical impairment with no reasonable expectancy of motor improvement
  • Prevalence of spastic or peripheral deficits
  • Any impairment of general conditions (such as severe breathing and nutrition difficulties, vital parameters instability) that may make risky the trial

Preliminary results
To date ten patients (seven females and three males), with the age ranging from 3 to 16 years old, have been enrolled with the following diagnosis :

  • Alexander disease: 1 patient,
  • Pelizaeus-Merzbacher or Pelizaeus Merzbacher like disease: 2 patients,
  • Metachromatic leukodystrohy: 3 patients,
  • Vanishing white matter disease: 1 patient,
  • Krabbe disease: 1 patient,
  • Unclassified primary leukodystophies: 2 patients.

A slight improvement in social interaction and motor symptoms (bradykinesia improvement, an expansion in movement repertoires and motor fluency). Our preliminary data seems to support previous studies concerning a marginal but real role of L-DOPA in treating target movement disorders symptoms in white matter diseases.

Contact: Vincenzo Leuzzi, phone: +390644712282 / e-mail: vincenzo.leuzzi@uniroma1.it