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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
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| Name | Class |
|---|---|
| Foundation for Prader-Willi Research | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Coenzyme Q10 | Dietary Supplement | 6 week trial of either treatment with CoenzymeQ. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Vertical Jump Test | Change in the baseline jumping height (centimetres) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximal Work (measured in watts ) from incremental cycle ergometry | Change in the amount of work (measured in watts) in a bicycle ride to exhaustion. Participants will ride a stationary bicycle (cycle ergometer) until unable to continue. Workloads will progressively increase every minute from 'easy to pedal' to 'very hard to pedal' until participants are unable to sustain the pedalling for 1 minute. The higher the watts, the more work the participant is able to do. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ingrid Tein, MD | The Hospital for Sick Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Hospital for Sick Children | Toronto | Ontario | M5G1X8 | Canada |
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| ID | Term |
|---|---|
| D011218 | Prader-Willi Syndrome |
| ID | Term |
|---|---|
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C024989 | coenzyme Q10 |
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prospective, randomized, double-blind, controlled, cross-over study with CoQ10 and placebo arms
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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
| Placebo |
| Other |
6 week trial of either treatment with Placebo |
|
Change in the baseline hand grip strength (kg)
| 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 | 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). | 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 | 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. | 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. | 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. | 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. | Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo) |
| 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 | Change in muscular phosphocreatine ((PCr) measured by 31P-Magnetic Resonance Spectroscopy) while performing bicycle exercise in the Magnetic Resonance scanner. | 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 | Change in aerobic capacity (oxygen uptake (VO2) ml/kg/min) will be measured in a bicycle ride to exhaustion. Workloads will progressively increase every minute from 'easy to pedal' to 'very hard to pedal' until participants are unable to sustain the pedalling for 1 minute. Participants will breathe through a low resistance breathing valve and inspired and expired concentrations of oxygen and carbon dioxide will be measured to determine VO2. The higher the VO2, the higher the aerobic capacity (physical fitness). | week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo) |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D000096803 | Imprinting Disorders |
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |