Mitochondrial Complex I Dysfunction in PWS

NCT03831425 | Withdrawn Phase 2 DMC

• 1 other identifier: 1000053066
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prader-Willi Syndrome

Keywords

CoQ10; muscle function; attention span; quality of life

Outcome Measures

Primary Outcomes (1)

• Three minute step test

  Change in the baseline number of steps in 3 minutes of testing

  Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

Secondary Outcomes (9)

• Vertical Jump Test

  Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

• Hand Grip Test

  Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

• 6 Minute walk test

  Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

• Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale

  Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

• Three Day Physical Activity Record (3DPAR)

  Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

Other Outcomes (3)

• Maximal Work (measured in watts ) from incremental cycle ergometry

  week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

• 31-phosphorus magnetic resonance spectroscopy (MRS) ergometry

  week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

• Maximal Aerobic Capacity (Oxygen Uptake (VO2) in milliliters per kilogram body weight per minute)from incremental cycle ergometry

  week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)

Study Arms (2)

Coenzyme Q

EXPERIMENTAL

Each patient will be asked to take part in a 6 wk trial of pharmaceutical grade CoQ10 and will be randomly assigned to a start time. There will be a 6 wk washout period between treatment and placebo arms. At baseline, if this is the first arm, testing will include determination of muscle function based on our 3 min step test, muscle power (maximal jump, handgrip), strength (Queens' Square), endurance (6MWT), fatigue (PedsQL fatigue scale), physical activity level (3DPAR), attention (ADHDT scale), cognition (MoCA), physical function (CHAQ).and quality of life (PedQL). Following the 6 wk CoQ10 trial, testing will include repeat determination of all of the above as well as determination of total aerobic capacity (maximum cycle ergometry) and muscle metabolism (31P-MRS ergometry).

Dietary Supplement: Coenzyme Q10

Placebo

PLACEBO COMPARATOR

Each patient will be asked to take part in a 6 wk trial of placebo and will be randomly assigned to a start time. There will be a 6 wk washout period between treatment and placebo arms. At baseline, if this is the first arm, testing will include determination of muscle function based on our 3 min step test, muscle power (maximal jump, handgrip), strength (Queens' Square), endurance (6MWT), fatigue (PedsQL fatigue scale), physical activity level (3DPAR), attention (ADHDT scale), cognition (MoCA), physical function (CHAQ).and quality of life (PedQL). Following the 6 wk placebo trial, testing will include repeat determination of all of the above as well as determination of total aerobic capacity (maximum cycle ergometry) and muscle metabolism (31P-MRS ergometry).

Other: Placebo

Interventions

Coenzyme Q10 DIETARY_SUPPLEMENT

6 week trial of either treatment with CoenzymeQ.

Coenzyme Q

Placebo OTHER

6 week trial of either treatment with Placebo

Placebo

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Consent provided
• patients with genetically confirmed PWS aged 13 to 18 years (n=14)
• ability to cooperate with exercise testing
• weight \> 35.0 kg
• in good general health as evidenced by medical history
• able to take oral medications
• for females of reproductive potential, use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of study intervention administration
• for males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 8 weeks after the end of study intervention administration

You may not qualify if:

• unable to perform exercise tests,
• already taking CoQ10
• having liver disease or bile duct blockage,
• having thyroid disease or taking thyroid medications
• presence of diabetes
• taking antiarrhythmics or antihypertensives or anti-failure medications
• presence of gastric disorders
• presence of skin disorders
• pregnancy or lactation
• lactose intolerance
• known allergic reaction to CoQ10 or components of preparation.
• treatment with another investigational drug or other intervention
• current smoker or tobacco use within 6 months
• current cannabis user or use within 6 months
• presence of chronic respiratory disease other than asthma

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Foundation for Prader-Willi Research: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Prader-Willi Syndrome

Interventions

coenzyme Q10

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Ingrid Tein, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Sick Kids research pharmacist will be responsible for dispensing the CoQ10 capsules which will be of highest grade, purity and safety from Webber Natural Pharmaceuticals Limited. A placebo will be prepared by the Sick Kids research pharmacy and will consist of lactose-filled capsules. The CoQ10 and placebo capsules will not be identical in colour, shape or taste. However, as stated above, researchers, participants and families will be blinded to the treatment phase. They will know they are receiving one capsule for one part of the study and another capsule for the next part. No one (except the pharmacist and an unblinded study team member, who will only distribute and collect the medication given to the family (will not conduct any testing)) will know which capsule contains CoQ10 and which contains the placebo
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Neurometabolic Clinic, Staff Neurologist, Division of Neurology, Principal Investigator, Senior Associate Scientist, Genetics and Genome Biology Program

Model Details: prospective, randomized, double-blind, controlled, cross-over study with CoQ10 and placebo arms

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: February 5, 2019
• Study Start: June 1, 2023
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)