Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

• ClinicalTrials.gov Identifier: NCT01668186
• Recruitment Status: Recruiting
• First Posted: August 17, 2012
• Last Update Posted: November 5, 2020
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Information provided by (Responsible Party): Nancy Braverman, McGill University Health Centre/Research Institute of the McGill University Health Centre

Tracking Information

• First Submitted Date: August 10, 2012
• First Posted Date: August 17, 2012
• Last Update Posted Date: November 5, 2020
• Study Start Date: January 2012
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2015)

Documentation of the clinical findings [ Time Frame: Yearly up to 10 years ]

Clinical findings include but are not limited to: life span, growth parameters, development, vision, hearing, neurological examinations, renal problems, adrenal function, skeletal problems, and any other system involvement.

Original Primary Outcome Measures (submitted: August 14, 2012)

• Documentation of the clinical findings [ Time Frame: Yearly up to 10 years ]
  Clinical findings include life span, growth, development, vision, hearing, neurological examinations, renal problems, adrenal problems skeletal problems and any other system involvement.
• Peroxisome function testing [ Time Frame: yearly up to 10 years ]
  To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, urine oxalate
• Identification of PEX gene mutations [ Time Frame: once ]

Current Secondary Outcome Measures (submitted: February 26, 2020)

• Peroxisome function testing [ Time Frame: Yearly up to 10 years ]
  To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, and urine oxalate.
• Development of leukodystrophy [ Time Frame: Yearly up to 10 years ]
  Identification of patterns and course by MRI
• Scoring of fundus photography (OCT and FAF) [ Time Frame: Yearly up to 10 years ]
  Identification of patterns and course
• Genotype-phenotype correlation [ Time Frame: Yearly up to 10 years ]
  Correlation of mutation type to peroxisome biochemistry, number and type of disease complications.
• Frequency of various disease complications and identification of risk factors in the PBD population [ Time Frame: Yearly up to 10 years ]
  Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones
• Development of care management guideline resource for adolescents and adults with PBD-ZSD [ Time Frame: Yearly up to 10 years ]
  Medical issues (Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones), main challenges, and the pediatric-to-adult transition experience will be included in PBD-ZSD adult-specific management guidelines

Original Secondary Outcome Measures (submitted: August 14, 2012)

• Development of leukodystrophy [ Time Frame: Yearly up to 10 years ]
  Identification of patterns and course by MRI
• Scoring of fundus photography [ Time Frame: Yearly up to 10 years ]
  Identification of patterns and course
• Correlation of phenotype with genotype [ Time Frame: Yearly up to 10 years ]
• Frequency in the population of various disease complications [ Time Frame: Yearly up to 10 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
• Official Title: Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
• Brief Summary: The Peroxisome Biogenesis Disorders (PBD) are a group of inherited disorders due to defects in peroxisome assembly causing complex developmental and metabolic sequelae. In spite of advancements in peroxisome biology, the pathophysiology remains unknown, the spectrum of phenotypes poorly characterized and the natural history not yet systematically reported. Our aims are to further define this population clinically, biochemically and genetically. The investigators will prospectively follow patients from Canada, the US and internationally, and collect data from medical evaluations, blood, urine and imaging studies that would be performed on a clinical care basis. For patients who are unable to attend our clinic, we will collect all medical records and images since birth as well as subsequent records/images for the next 5 years or until the end of the study. Clinical data from medical records will be banked in our Peroxisomal Disorder Research Databank and Biobank. The investigators will use this information to identify standards of care and improve management.
• Detailed Description: Participants have the option to be seen in consultation at the McGill University Health Centre in Montreal, Canada, on a yearly basis. This includes a consultation in Genetics, Nutrition, Neurology, and Ophthalmology (OCT and FAF exams). All medical records and images will be collected, retrospectively and prospectively, until the end of the study, and entered anonymously in a database. Biospecimens will be collected to identify new biomarkers. Candidate drugs will be evaluated for recovery of peroxisome functions in cultured fibroblasts.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Other
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

blood, dried blood spots, urine, and specimens obtained for other e.g. cultured fibroblasts, liver biopsies

• Sampling Method: Non-Probability Sample
• Study Population: Any patient with a PBD diagnosis- or related single enzyme/protein defect

Condition

• Peroxisome Biogenesis Disorder
• Zellweger Spectrum Disorder
• RCDP - Rhizomelic Chondrodysplasia Punctata
• D-Bifunctional Protein Deficiency
• Alpha-Methylacyl-CoA Racemase Deficiency
• Peroxisomal Acyl-CoA Oxidase Deficiency
• Peroxisomal Acyl-CoA Oxidase 2 Deficiency
• ATP Binding Cassette Subfamily D Member 3 Gene Mutation
• ACBD5 (AcylCoA Binding Domain 5) Deficiency
• Adult Refsum Disease
• Sterol Carrier Protein 2 Deficiency

• Intervention: Not Provided

Study Groups/Cohorts

Patients diagnosed with PBD

Collection of medical records and images (ultrasounds, X-rays, MRIs, CT scans, ophthalmic images), Next-generation panel, Drug screening, and Consultation

Publications *

• Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/
• Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar;117(3):313-21. doi: 10.1016/j.ymgme.2015.12.009. Epub 2015 Dec 23. Review.
• Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober M. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/
• Rush ET, Goodwin JL, Braverman NE, Rizzo WB. Low bone mineral density is a common feature of Zellweger spectrum disorders. Mol Genet Metab. 2016 Jan;117(1):33-7. doi: 10.1016/j.ymgme.2015.11.009. Epub 2015 Nov 24.
• Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH. A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Oct;20(10):1274-1283. doi: 10.1038/gim.2017.262. Epub 2018 Feb 8.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 21, 2018): 150
• Original Estimated Enrollment (submitted: August 14, 2012): 100
• Estimated Study Completion Date: January 2022
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of PBD or
• Single peroxisome enzyme/protein defect with phenotype similar to PBD

Exclusion Criteria:

• Not a PBD
• Not a single peroxisome enzyme/protein defect with phenotype similar to PBD

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Nancy E Braverman, MD, MS; (1) 514-934-1934 ext 23404; nancy.braverman@mcgill.ca

Contact: Yasmin D'Souza, MSc, PhD; (1) 514-934-1934 ext 23403; pbd.genetics@mcgill.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01668186
• Other Study ID Numbers: 11-090-PED
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Nancy Braverman, McGill University Health Centre/Research Institute of the McGill University Health Centre
• Study Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nancy E Braverman, MD, MS; McGill University Health Center, Montreal Childrens Hopital

• PRS Account: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Verification Date: November 2020