Prader-Willi SyndromePhase 2NCT03831425
Mitochondrial Complex I Dysfunction in PWS
A Phase 2 study testing Coenzyme Q10 in people with Prader-Willi Syndrome, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 18 years
- Conditions the study is for
- Prader-Willi Syndrome
- What is being tested?
- Coenzyme Q10
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jun 2023to Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 13 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
- presence of cardiac disease with cardiac insufficiency/CHF
- presence of MR-incompatible metal in body, metal devices or tattoos
- presence of a bleeding disorder
- gelatin intolerance
- clinically significant findings in laboratory tests at screening
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mitochondrial Complex I Dysfunction in Prader Willi Syndrome: A New Therapeutic Target
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.
Read the 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
- Being tested
- Coenzyme Q10, Placebo
- Keywords
- CoQ10, muscle function, attention span, quality of life
- Medical subject headings
- Prader-Willi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coenzyme Q10Dietary supplement
6 week trial of either treatment with CoenzymeQ.
PlaceboOther
6 week trial of either treatment with Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Three minute step test
Change in the baseline number of steps in 3 minutes of testing
Measured: 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
Change in the baseline jumping height (centimetres)
Measured: 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
Change in the baseline hand grip strength (kg)
Measured: 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
Change in baseline number of metres walked in 6 minutes
Measured: 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
Change in the baseline multi-dimensional fatigue scale; total score is reported. The higher the number, the greater the fatigue (range from 0 to 72).
Measured: 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)
Change in the baseline three day recall of time (number of minutes) spent at rest, and in light, moderate and vigorous activity
Measured: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
SWAN Rating Scale for Attention Deficit Hyperactivity Disorder (ADHD)
Change in the baseline total reported score (out of 18 items). If the sum of items 1-9 is 6 or greater, the child is likely ADHD-Inattentive type. If the sum of items 10-18 is 6 or greater, the child is likely ADHD-Hyperactive/Impulsive type. If both the sums of 1-9 and 10-18 are 6 or greater, the child is likely ADHD combined type.
Measured: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Montreal Cognitive Assessment (MOCA)
Change in the baseline total cognitive score out of 30 points (range 0 to 30). The higher the number, the better the cognition.
Measured: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Childhood Health Assessment Questionnaire (CHAQ)
Change in the baseline CHAQ score. Assessment of how an illness or condition affects child's ability to function in daily life. There are individual items in each of 8 sections (Arising, Eating, Dressing, Walking, Hygiene, Reach, Grip, Activities). Scoring of individual items ranges from 0-3 (0=from no difficulty to 3= unable to do). The higher the score, the more difficult is the task to a maximum of 3 points for each section. For each of the 8 sections, whatever the highest individual score was becomes the score of the section (max 3 points). Points are added to the section score if devices or aids are used for that section (to a maximum of 3 points). The CHAQ score is the total of the 8 sections, divided by 8 with a range from 0 points (no impact on quality of life) to 3 (large impact on quality of life) . The higher the score, the greater the impact of the illness on function.
Measured: 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 Index (PedQL)
Change in baseline child quality of life using pictorial scales and comparators. The lower the score, the worse the quality of life. This is scored out of 10 cm.
Measured: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2019
- Study start1 Jun 2023 (estimated)
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
Why it stopped: unable to recruit despite multiple rounds of recruitment due to (1) not meeting inclusion/exclusion criteria (2) unwilling to participate during pandemic (3) living outside Toronto (4) involved in other PWS studies (5) no response to our messages X 3
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prader-Willi SyndromeStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- prospective, randomized, double-blind, controlled, cross-over study with CoQ10 and placebo arms
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Prader-Willi Research
- Responsible party
- Principal investigator, Ingrid Tein, The Hospital for Sick Children
- Investigators
- Ingrid Tein, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03831425
- Sponsor's protocol ID
- 1000053066
- Status last verified
- Jun 2024
- First submitted
- 22 Jan 2019
- Last updated
- 18 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitochondrial Complex I Dysfunction in Prader Willi Syndrome: A New Therapeutic Target
- ClinicalTrials.gov ID
- NCT03831425
- Acronym / sponsor ID
- 1000053066
- Conditions
- Prader-Willi Syndrome
- Keywords
- CoQ10, muscle function, attention span, quality of life
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: unable to recruit despite multiple rounds of recruitment due to (1) not meeting inclusion/exclusion criteria (2) unwilling to participate during pandemic (3) living outside Toronto (4) involved in other PWS studies (5) no response to our messages X 3
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Foundation for Prader-Willi Research
- Study start
- 1 Jun 2023 (estimated)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 5 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- prospective, randomized, double-blind, controlled, cross-over study with CoQ10 and placebo arms
| Arm | Type | Receives |
|---|---|---|
| Coenzyme Q | Experimental | Dietary Supplement: Coenzyme Q10Each 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). |
| Placebo | Placebo comparator | Other: PlaceboEach 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). |
Who may qualify
- Ages
- 13 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (20 listed)
- 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
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 |
|---|---|---|
| Coenzyme Q106 week trial of either treatment with CoenzymeQ. | Dietary supplement | Coenzyme Q |
| Placebo6 week trial of either treatment with Placebo | Other | Placebo |
Primary outcome
Three minute step test
Time frame: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Change in the baseline number of steps in 3 minutes of testing
9 secondary outcomes
Vertical Jump Test
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
SWAN Rating Scale for Attention Deficit Hyperactivity Disorder (ADHD)
Time frame: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Montreal Cognitive Assessment (MOCA)
Time frame: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Childhood Health Assessment Questionnaire (CHAQ)
Time frame: 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 Index (PedQL)
Time frame: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Individual participant dataSharing planned: No
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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.
Ingrid Tein, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Coenzyme Q10 in people with Prader-Willi Syndrome, run by The Hospital for Sick Children 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 8 inclusion and 20 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: withdrawn, as of the sponsor's last update on 18 Jun 2024. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Three minute step test (time frame: Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jun 2024.