Phase 3 N=12 Treatment

Betaine and Peroxisome Biogenesis Disorders

Peroxisome Biogenesis Disorders

Bottom Line

View on ClinicalTrials.gov: NCT01838941 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jun 2016

Primary outcome: Primary: Peroxisome Biochemical Functions as Measured by Plasma Very Long Chain Fatty Acid — 0.180; 0.188 ratio

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Betaine (Drug)
Age: Pediatric, Adult, Older Adult
Sex: All
Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Primary completion: Jan 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Peroxisome Biochemical Functions as Measured by Plasma Very Long Chain Fatty Acid	0.180; 0.188	—
SECONDARY Developmental Status	—	—

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.

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) < 0.07
PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD)
Genotype PEX1-G843D/G843D, 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/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null
Patient already treated with betaine

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01838941). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.