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NCT Number: NCT01838941

Betaine and 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.

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Key information

Conditions

Peroxisome Biogenesis Disorders Abnormalities, Multiple Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Kidney Diseases Liver Diseases Male Urogenital Diseases Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Peroxisomal Disorders Refsum Disease, Infantile Urogenital Diseases Urologic Diseases Zellweger Syndrome

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

About this study

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. 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 developed a laboratory-based research test aimed 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Betaine

Drug

Betaine will be given orally (mixed with food or dissolved in water, juice, milk, or formula) or through gastrostomy tube as follows:

  • 6 g/day in children < 30 kg, in 3 divided doses (2 g at meal time)
  • 12 g/day in children > 30 kg, in 4 divided doses (3 g at meal time and bed time).

Other names: Cystadane®

Primary outcomes

  1. Peroxisome Biochemical Functions as Measured by Plasma Very Long Chain Fatty Acid

    Time frame: 6 months

    C26/C22 ratio in plasma is a recognized biomarker for very long chain fatty acid (normal range: 0.002-0.018). It was measured twice before the beginning of treatment and measured once at the end.

Secondary outcomes

  1. Developmental Status

    Time frame: 6 months

    Denver Developmental Screening Test expressed in years and months.

Sponsors and collaborators

Lead sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

Other

Collaborators

  • Children's Hospital and Medical Center, Omaha, Nebraska

Registry information

Official study title

A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders.

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Apr 24, 2013
Registry last updated
Jun 28, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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