NCT03831425

Mitochondrial Complex I Dysfunction in PWS

Mitochondrial Complex I Dysfunction in Prader Willi Syndrome: A New Therapeutic Target

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: The Hospital for Sick Children · Academic / Other
• Sex: All
• Age: 13 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

Prader-Willi Syndrome (PWS) is characterized by profound infantile hypotonia, growth delay, cognitive impairment, muscle weakness and exercise intolerance. Studies have suggested that a defect in energy metabolism, yet to be clarified, may be involved in its pathogenesis. Many PWS patients have received Coenzyme Q10, but the rationale for this and objective impact on cellular metabolism has not been clarified.

Detailed description

Investigators will determine the clinical efficacy of CoQ10 in a prospective, randomized, double-blind, controlled, cross-over study. Primary outcome will include determination of muscle function based on a 3 minute step test which showed good sensitivity in the investigators' pilot study. Secondary outcomes will determine effects on muscle power (maximal vertical jump), strength (hand grip), endurance (6 Minute Walk Test), fatigue (PedsQL quality of life scale), physical activity level (3DPAR), attention (ADHDT), cognition (MOCA), and physical function (CHAQ). The investigators' subaim is to elucidate the pathophysiologic mechanisms by which clinical improvements are mediated through interrogation of underlying mitochondrial dysfunction to optimize therapies. This will include determination of total aerobic capacity (maximal graded cycle ergometry), muscle metabolic function (31P-magnetic resonance spectroscopy (MRS) of muscle to evaluate high energy phosphagen, anaerobic and aerobic exercise metabolism), mitochondrial function (serum lactate, carnitine, acylcarnitines, lactate/pyruvate ratio), and blood and urine oxidative stress markers of lipid, protein and DNA peroxidation. Investigators hypothesize that CoQ10 will lead to a clinically significant improvement in motor function, power, fatigue, habitual activity, attention span \& thereby quality of life in PWS.

Conditions

• Prader-Willi Syndrome

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Coenzyme Q10	6 week trial of either treatment with CoenzymeQ.
OTHER	Placebo	6 week trial of either treatment with Placebo

Timeline

• Start date: 2023-06-01
• Primary completion: 2024-06-01
• Completion: 2024-06-01
• First posted: 2019-02-05
• Last updated: 2024-06-18

Locations

1 site across 1 country: Canada