Hydroxychloroquine Administration for Reduction of Pexophagy (HARP)
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|ClinicalTrials.gov Identifier: NCT03856866|
Recruitment Status : Completed
First Posted : February 27, 2019
Last Update Posted : December 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Zellweger Syndrome Peroxisome Biogenesis Disorders||Drug: Hydroxychloroquine Drug: Placebo||Phase 2|
HARP is a phase II/III, double-blind, placebo-controlled, randomized, crossover series N-of-1 study of the effect of hydroxychloroquine (HCQ) in patients with peroxisomal biogenesis disorders (PBD-ZSD). Patients eligible for the study must have a laboratory diagnosis of PEX1, PEX6 or PEX26 dependent PBD-ZSD from a CLIA or SCC-certified clinical laboratory, a history of abnormal VLCFA levels, and must be at least 84 days from their last HCQ dose. Patients will be excluded for known sensitivity to HCQ, known glucose-6-phosphate dehydrogenase deficiency, if they have an expected survival of less than 9 months or if they are participating in another interventional clinical trial.
HCQ will be administered at a dose of 4mg/kg/day divided into two doses, as a liquid suspension that can be given orally or through nasogastric or gastric tube. Within the study, HCQ or placebo will be given for 84 days, followed by a washout period of 84 days followed by an 84 day crossover to the alternative therapy to assess the effect the study measures.
Study measures will be completed at four intervals (initiation, end of period 1, start of period 2, end of trial). Ophthalmological monitoring of patients has three components, electroretinogram (ERG), visual acuity testing and optical coherence tomography (OCT). Plasma levels of very long-chain fatty acids (VLCFA), plasmalogen and phytanic acid will be assessed. Parents will also be administered The Pediatric Inventory for Parents (PIP), a questionnaire that was developed to evaluate the stress associated with parenting a seriously ill child, at the end of period 1 and period 2.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||A randomized, blinded, placebo controlled, crossover N of 1 trial.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||All parties will be masked except for research pharmacy who will do the randomization.|
|Official Title:||Hydroxychloroquine Administration for Reduction of Pexophagy|
|Actual Study Start Date :||January 11, 2019|
|Actual Primary Completion Date :||May 5, 2020|
|Actual Study Completion Date :||May 5, 2020|
Hydroxychloroquine: liquid suspension, 4mg/kg/day by mouth, divided bid for 84 days.
Hydroxychloroquine: 4mg/kg/day, divided bid.
Placebo Comparator: Placebo
Liquid suspension compounded to mimic the taste, appearance and texture of the investigational agent.
Liquid suspension compounded to mimic the active hydroxycholoquine interventional agent.
- Electroretinogram (ERG) voltage changes. [ Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm. ]Electroretinograms are a diagnostic test that measures the electric activity within cells in response to stimulus. ERG voltages are depressed in peroxisomal disease, and the quantitative evaluation of ERG voltage is another measure that has been used as an endpoint for clinical trials in peroxisomal disease. Change in b-wave voltage before and after treatment period.
- Change in the red blood cell levels of plasmalogen. [ Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm. ]Change in the red blood cell levels of plasmalogen (18:0 dimethylacetals/18:0 ratio).
- Change in the plasma levels of phytanic acid. [ Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm. ]Change in the plasma levels of phytanic acid.
- Change in the plasma levels of very-long chain fatty acids. [ Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm. ]Change in the plasma levels of very-long chain fatty acids (C26/C22).
- Eye examination: Optical Coherence Tomography [ Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm. ]Optical coherence tomography is an imaging study of the retina. OCT is routinely performed in clinical management of patients with peroxisomal disease.
- Eye examination: Visual Acuity [ Time Frame: 12 week. Measurements at Day 0, Day 84(+/-7 days) of each treatment arm. ]Visual acuity testing evaluates the visual performance of patients using the reading of a logMAR chart. Visual acuity testing is routinely performed in clinical management of patients with peroxisomal disease.
- Pediatric Inventory for Parents (PIP) following the treatment arms. [ Time Frame: 36 week. Measurements following each treatment arm. ]The PIP is a validated measure of parental stress related to the care for children with chronic illness.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03856866
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G1X8|
|Principal Investigator:||Neal Sondheimer, MD||The Hospital for Sick Children|