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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
6 week trial of either treatment with CoenzymeQ.
6 week trial of either treatment with Placebo
The Hospital for Sick Children
Toronto, Ontario, Canada
Three minute step test
Change in the baseline number of steps in 3 minutes of testing
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)
Vertical Jump Test
Change in the baseline jumping height (centimetres)
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
Change in the baseline hand grip strength (kg)
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
Change in baseline number of metres walked in 6 minutes
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
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).
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)
Change in the baseline three day recall of time (number of minutes) spent at rest, and in light, moderate and vigorous activity
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)
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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.
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)
Change in the baseline total cognitive score out of 30 points (range 0 to 30). The higher the number, the better the cognition.
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)
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.
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)
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.
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)