The Effects of Home-based Exercise Training and Multi-ingredient Supplementation on Functional Outcomes and Skeletal Muscle Adaptations in Patients With Myotonic Dystrophy Type 1
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- VO2 Max
研究概览
简要总结
Myotonic dystrophy type 1 (DM1) is a rare genetic disease that affects about 1 in 2100 people. Patients diagnosed with DM1 present with many symptoms, however, their muscles are mainly affected. DM1 patients experience a gradual loss of muscle, followed by an increase in body fat percentage, which makes them weaker, resulting in difficulties to perform activities of daily living, such as climbing stairs, and understandably, this affects their quality of life. DM1 currently does not have a cure. Therefore, it is very important to find ways in which we can help DM1 patients to improve their symptoms, and hopefully, improve their quality of life, and possibly improve disease prognosis. Exercise is known to improve muscle quality and function. In addition, we hypothesize that a multi-ingredient supplement (MIS) for muscle health and antioxidants for fat loss, might show improved benefits on top of exercise. Therefore, we will investigate the effects of 16-week home-based concurrent training, with MIS or placebo, on body composition, and functional measures. Lastly, we will investigate muscle adaptations in DM1 and following study intervention
详细描述
The present study will target patients (male and female) that have been clinically diagnosed with myotonic dystrophy type 1 with 100-1000 CTG repeats, between the ages of 19 - 60. In addition, a healthy population will serve as baseline controls, and they will be matched for age and sex, to the DM1 patients.
A total of 40 DM1 patients and 20 healthy controls will be recruited. DM1 patients will be randomized to 20 in the active group and 20 in the placebo. Both males and females will be recruited, targeting 20 males and 20 females. Corresponding 10 healthy males and 10 healthy females will be matched for sex and age, and only participate in baseline visits, measures, and sample collection.
Home-based concurrent training (HBCT) represents an exercise intervention with minimal barriers to entry. Our study will assess the effectiveness of this intervention, in combination with a multi-ingredient supplement (MIS) containing protein, creatine, antioxidants, and other dietary supplements in patients with DM1, in improving functional, clinical, and strength measures, as well as the quality of life, as assessed by scores in questionnaires. In addition, we will investigate adaptations to skeletal muscle following HBCT and MIS.
A randomized clinical trial of DM1 patients. Our study will include exercise as the over-arching intervention, with two groups nested within, DM1 patients randomized to MIS and placebo, both of which will undergo 16 weeks of home-based exercise training. Measurements and samples will be collected before and after the study intervention. A third group will include age and sex-matched healthy controls. This group will not undergo training + supplement intervention and will be used for baseline comparisons between healthy participants and DM1 patients.
Study procedures will include blood draws and muscle biopsies in each visit. In addition, participants will be asked to undergo a cardiorespiratory fitness test (VO2MAX test), a battery of functional tests (6-minute walk test, 5x sit-to-stand, one leg standing, 4-stair climb), strength testing (grip strength and knee extension tests) and lastly, clinical procedures, including ECGs and spirometry. Measurements and sample collection will be done before and after the study intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Both the participants and the investigators are blinded to the active and placebo groups. A third party, Gruppo Nutrition (Windsor, ON) will conduct the randomization for our supplemental interventions and manage blinding procedures. Neither the participants nor the investigators will be unblinded to the supplement randomization. Lastly, researchers will only be unblinded upon finishing the data analysis.
入排标准
- 年龄范围
- 19 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age and sex-matched controls inclusion criteria:
- •Healthy men and women
- •Normal BMI (BMI 18.5 - 24.9 kg/m2)
- •Inclusion Criteria for DM1 patients:
- •Male or female clinically diagnosed with DM1 (age 19 - 60 y).
- •CTG repeats 100-
- •Normal weight (BMI 18.5 - 24.9 kg/m2) or overweight (BMI 25 - 29.9 kg/m2).
- •Physically inactive (< 1 hour of formal exercise/week).
- •6-minute walk test score between 250 - 500 meters
- •ECG with PR interval < 225 ms and QRS duration < 125 ms.
排除标准
- •for DM1 patients:
- •Obese (BMI > 30.0 kg/m2)
- •Physically active (> 1-2 hour of formal exercise/week)
- •6-minute walk test score <250 meters, chronic (> 2 weeks)
- •Use of narcotic analgesic or anti-inflammatory drugs
- •Type 1 or 2 diabetes (more than one anti-diabetic drug)
- •Cardiovascular disease (recent myocardial infarction (< 6 months)
- •Uncontrolled hypertension requiring more than 2 medications.
- •Congestive heart failure requiring more than one medication for control.
- •Cardiac conduction block (as above)
- •Renal disease (creatinine > 140)
- •Known liver disease
- •Cognitive impairments limiting ability to provide informed consent
- •Previous stroke with residual hemiparesis
- •Active musculoskeletal injuries and/or severe osteoarthritis
- •Significant weight loss in the 3-month period prior to the study
- •Severe peripheral neuropathy
- •Severe osteoporosis
- •Use of medications known to affect protein metabolism (i.e. corticosteroids)
- •Chronic obstructive or restrictive pulmonary disease (FVC < 70% of age predicted mean value)
- •Asthma requiring more than two medications.
研究组 & 干预措施
DM1 + HBEXT + MIS
Participants will be asked to undergo 16 weeks of home-based training and asked to take one dose of a multi-ingredient supplement per day.
干预措施: Mult-ingredient supplement (Dietary Supplement)
DM1 + HBEXT + MIS
Participants will be asked to undergo 16 weeks of home-based training and asked to take one dose of a multi-ingredient supplement per day.
干预措施: Concurrent exercise training (Behavioral)
DM1 + HBEXT + PLA
Participants will be asked to undergo 16 weeks of home-based training and asked to take one dose of a multi-ingredient supplement placebo per day.
干预措施: Placebo (Dietary Supplement)
DM1 + HBEXT + PLA
Participants will be asked to undergo 16 weeks of home-based training and asked to take one dose of a multi-ingredient supplement placebo per day.
干预措施: Concurrent exercise training (Behavioral)
CONTROL
Healthy control subjects who will not undergo study intervention and will be used for baseline measurements and outcomes.
结局指标
主要结局
VO2 Max
时间窗: 4 months from enrolment
Changes in cardiorespiratory fitness proxy measure as assessed via VO2 max testing
Body Composition Index
时间窗: 4 months from enrolment
Changes in ratio of fat-free mass to fat mass index as assessed via DEXA scan
次要结局
- Grip strength(4 months from enrolment)
- 6-minute walk test(4 months from enrolment)
- Timed up and go(4 months from enrolment)
- 5x sit to stand(4 months from enrolment)
- Leg muscle strength(4 months from enrolment)
- Muscle fibre cross sectional area(4 months from enrolment)
- Single leg stance test(4 months from enrolment)
- Muscle stem cell mitochondrial function(4 months from enrolment)
研究者
Mark Tarnopolsky
Principal Investigator, Professor, Director of Neuromuscular and Neurometabolic Clinic
McMaster University