Trial record 3 of 3 for:    Infantile Refsum Disease

Betaine and Peroxisome Biogenesis Disorders

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2013 by McGill University Health Center.
Recruitment status was  Recruiting
Orphan Europe
Information provided by (Responsible Party):
Nancy Braverman, McGill University Health Center Identifier:
First received: March 29, 2013
Last updated: August 7, 2013
Last verified: August 2013
The PBD are a rare group of inherited disorders due to the failure to form functional cellular peroxisomes. Most patients have progressive hearing and visual loss, leading to deafness and blindness, as well as neurological deterioration. There are no therapies for this disorder. A misfolded protein with residual function, PEX1-Gly843Asp, represents one third of all mutant alleles. Using patient cell lines with this mutation, we reported the recovery of peroxisome functions by treatment with Betaine, acting as a nonspecific chemical chaperone for the misfolded PEX1 protein. Betaine, or trimethylglycine, is a Health Canada and FDA approved orphan drug for the treatment of homocystinuria and is used by us safely and regularly in genetic medicine. We will perform a 6 month pilot study with 12 patients to test the hypothesis that Betaine, at recommended doses, can recover peroxisome biochemical functions in blood.

Condition Intervention Phase
Peroxisome Biogenesis Disorder (PBD)
Drug: Betaine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders.

Resource links provided by NLM:

Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Peroxisome biochemical functions as measured by plasma very long chain fatty acid [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    C26/C22 ratio in plasma which is a recognized biomarker for very long chain fatty acid.

Secondary Outcome Measures:
  • Growth developmental status [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Denver Developmental Screening Test expressed in years and months.

Estimated Enrollment: 12
Study Start Date: March 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Betaine

Betaine (Cystadane®), 6 g/day in children less than 30 kg in 3 divided doses (2 g, 3 times daily) , and 12 g/day in children over 30 kg, in 4 divided doses (3 g, 4 times daily).

Betaine will be given orally or through gastrostomy tube

Drug: Betaine

Detailed Description:

Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. When there is faulty peroxisome assembly, as in PBD, these important fats and lipids either accumulate or are not made. These changes result in abnormalities of organ formation that a child is born with, such as changes in bone, brain and eye formation. There is no specific treatment for these disorders, and management is supportive. In order to complement existing supportive therapies, physicians and researchers are still actively looking for new treatments acting on the root cause of PBD: the peroxisome function. To identify drugs that help recover peroxisome function a group of scientists have developed a test to be used in laboratories, aiming at reviewing the activity of the large number of potential treatments.

Using this test, they have uncovered that Betaine can improve the function of the peroxisome, when the defect is caused by a PEX1-Gly843Asp mutation, and as such may improve the overall health of child suffering from PBD.

Betaine is a medication already available as a powder for oral solution, for another rare disease. It is approved in many countries, including Health Canada for Canada and the Food and Drug Administration for the USA. Paediatric genetic physicians are used to prescribing this medication and know it well.

At the current stage of scientific knowledge, it is a critical next step to evaluate the benefit of betaine in children having a PBD due to a PEX1-Gly843Asp mutation, to ensure that the medication is safe and to measure the level of improvement of the function of the peroxisome.

Thus, the principal objective of the study is to determine the improvement in the key peroxisome functions (plasma very long chain fatty acid profiles red cell plasmalogen levels, plasma pipecolic acid levels and plasma bile acid profiles). Another objective is to measure the growth of your child and his / her development.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males or females
  • Any age
  • Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters:

    • Elevated plasma VLCFA (C26/22) > 0.02
    • Elevated plasma branched chain pristanic acid > 0.3 μg/ml
    • Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07
  • PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD)
  • Genotype PEX1-G843D/I700fs or PEX1-G843D and any second PEX1 mutation that is predicted to be null
  • Expected survival of at least 6 months

Exclusion Criteria:

  • Genotypes other than PEX1-G843D//I700fs or PEX1-G843D and any second PEX1 mutation that is predicted to be null
  • Patient already treated with betaine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01838941

Contact: Francois Plourde, MSc, MSc (1) 514 934 1934 ext 23403
Contact: Nancy Braverman, PhD, MD (1) 514 934 1934 ext 23404

Canada, Quebec
Montreal Children's Hospital Recruiting
Montreal, Quebec, Canada, H3H 1P3
Contact: Francois Plourde, MSc, MSc    514 934 1934 ext 23403   
Contact: Nancy Braverman, PhD,MD    514 934 1934 ext 23404   
Principal Investigator: Nancy Braverman, PhD, MD         
Sponsors and Collaborators
McGill University Health Center
Orphan Europe
Principal Investigator: Nancy Braverman, PhD, MD Montreal Children's Hospital, MUHC
  More Information

Responsible Party: Nancy Braverman, Associate Professor, Depts. of Human Genetics and Pediatrics, McGill University Health Center Identifier: NCT01838941     History of Changes
Other Study ID Numbers: RPGDN001 
Study First Received: March 29, 2013
Last Updated: August 7, 2013
Health Authority: Canada: Health Canada

Keywords provided by McGill University Health Center:
Peroxisome Biogenesis Disorder
neonatal adrenoleukodystrophy
infantile Refsum disease
PEX1 mutation

Additional relevant MeSH terms:
Peroxisomal Disorders
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Gastrointestinal Agents
Hypolipidemic Agents
Lipid Regulating Agents
Lipotropic Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 24, 2016