Betaine and Peroxisome Biogenesis Disorders

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Disease Information

Descriptive Information
Brief Title † Betaine and Peroxisome Biogenesis Disorders
Official Title † A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders.
Brief Summary 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.
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.
Study Phase Phase 3
Study Type † Interventional
Study Design † Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Measure † Peroxisome biochemical functions as measured by plasma very long chain fatty acid
Secondary Outcome Measure † Growth developmental status
Condition † Peroxisome Biogenesis Disorder (PBD)
Intervention † DrugBetaine
Study Arms / Comparison Groups 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
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 12
Start Date † March 2013
Completion Date June 2014
Primary Completion Date June 2014
Eligibility Criteria † 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)
Gender Both
Ages N/A - N/A
Accepts Healthy Volunteers No
Contacts †† Francois Plourde, MSc, MSc, (1) 514 934 1934,
Location Countries † Canada
Administrative Information
NCT ID † NCT01838941
Organization ID RPGDN001
Secondary IDs ††
Responsible Party Principal Investigator
Study Sponsor † McGill University Health Center
Collaborators †† Orphan Europe
Investigators † Principal Investigator: Nancy Braverman, PhD, MD, Montreal Children's Hospital, MUHC
Information Provided By
Verification Date August 2013
First Received Date † March 29, 2013
Last Updated Date August 7, 2013
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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