Peroxisome Biogenesis Disorder (PBD) Clinical Trial
Official title:
A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders.
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.
Status | Recruiting |
Enrollment | 12 |
Est. completion date | June 2014 |
Est. primary completion date | June 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A and older |
Eligibility |
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 |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Canada | Montreal Children's Hospital | Montreal | Quebec |
Lead Sponsor | Collaborator |
---|---|
McGill University Health Center | Orphan Europe |
Canada,
Zhang R, Chen L, Jiralerspong S, Snowden A, Steinberg S, Braverman N. Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds. Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5569-74. doi: 10.1073/pnas.0914960107. Epub 2010 Mar 8. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Peroxisome biochemical functions as measured by plasma very long chain fatty acid | C26/C22 ratio in plasma which is a recognized biomarker for very long chain fatty acid. | 6 months | No |
Secondary | Growth developmental status | Denver Developmental Screening Test expressed in years and months. | 6 months | No |