Peroxisome Biogenesis DisordersPhase 3NCT01838941
Betaine and Peroxisome Biogenesis Disorders
A Phase 3 study testing Betaine in people with Peroxisome Biogenesis Disorders, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Peroxisome Biogenesis Disorders
- What is being tested?
- Betaine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2013to Jun 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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. 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.
- Conditions
- Peroxisome Biogenesis Disorders
- Being tested
- Betaine
- Keywords
- Peroxisome Biogenesis Disorder, PBD, neonatal adrenoleukodystrophy, infantile Refsum disease, PEX1 mutation, Betaine
- Medical subject headings
- Peroxisome biogenesis disorders, Zellweger Syndrome, Peroxisomal Disorders, Refsum Disease, Infantile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BetaineDrug
Also called Cystadane®
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).
| Study group | Role | What they receive |
|---|---|---|
| Betaine | Experimental | Betaine will be given orally to all participants and dose will be adjusted to body weight. Receives: Drug: Betaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peroxisome Biochemical Functions as Measured by Plasma Very Long Chain Fatty Acid
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.
Measured: 6 months
Secondary outcomes (1)
Developmental Status
Denver Developmental Screening Test expressed in years and months.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2013 (estimated)
- Study startMar 2013
- Primary completionJan 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peroxisome Biogenesis DisordersStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital and Medical Center, Omaha, Nebraska
- Responsible party
- Principal investigator, Nancy Braverman, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Nancy Braverman, PhD, MD, Principal investigator, Montreal Children's Hospital, MUHC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01838941
- Sponsor's protocol ID
- RPGDN001
- Status last verified
- May 2016
- First submitted
- 29 Mar 2013
- Last updated
- 28 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 20212125
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders.
- ClinicalTrials.gov ID
- NCT01838941
- Acronym / sponsor ID
- RPGDN001
- Conditions
- Peroxisome Biogenesis Disorders
- Keywords
- Peroxisome Biogenesis Disorder, PBD, neonatal adrenoleukodystrophy, infantile Refsum disease, PEX1 mutation, Betaine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Collaborators
- Children's Hospital and Medical Center, Omaha, Nebraska
- Study start
- Mar 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 24 Apr 2013 (estimated)
- Results
- Posted 28 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Betaine | Experimental | Drug: BetaineBetaine will be given orally to all participants and dose will be adjusted to body weight. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Males or females
- Any age
- Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters:
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BetaineAlso: Cystadane®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). | Drug | Betaine |
Primary outcome
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.
1 secondary outcome
Developmental Status
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20212125Zhang 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.
- Individual participant dataSharing planned: No
Related trials for Peroxisome Biogenesis Disorders
RecruitingObservational study
Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
Peroxisome Biogenesis Disorder, Zellweger Spectrum Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy Braverman, PhD, MD principal investigator
Montreal Children's Hospital, MUHC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Betaine in people with Peroxisome Biogenesis Disorders, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peroxisome Biochemical Functions as Measured by Plasma Very Long Chain Fatty Acid (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01838941, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2016; AzTrials last refreshed its copy on 6 Nov 2026.