Mitochondrial Complex I Dysfunction in Prader Willi Syndrome: A New Therapeutic Target
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Three minute step test
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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
入排标准
- 年龄范围
- 13 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
结局指标
主要结局
Three minute step test
时间窗: 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
次要结局
- SWAN Rating Scale for Attention Deficit Hyperactivity Disorder (ADHD)(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)(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))
- 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))
- 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))
- 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))
- 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))
- Childhood Health Assessment Questionnaire (CHAQ)(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)(Baseline, week 8 (after 6 weeks on study drug or placebo), [6 week washout], week 20 (after 6 weeks study drug or placebo))
研究者
Ingrid Tein
Director, Neurometabolic Clinic, Staff Neurologist, Division of Neurology, Principal Investigator, Senior Associate Scientist, Genetics and Genome Biology Program
The Hospital for Sick Children