Odified Ketogenic Diet in Patients With McArdle Disease Part B - a Placebo-controlled, Cross-over Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Change in mean heart rate
研究概览
简要总结
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that a modified ketogenic diet could be a potential treatment option, by providing ketones as alternative fuel substrates for working muscle.
This blinded, placebo-controlled, cross-over study will investigate the potential effects of an optimal modified ketogenic diet found in part A (75% fat, 15%protein, 10%carbohydrates) in patients with McArdle disease compared with a healthy balanced placebo diet (>100grams of carbohydrates per day).
详细描述
A blinded randomized, placebo-controlled, cross-over study to investigate the effects of a modified ketogenic diet in patients with McArdle disease.
McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis. Currently, there are no satisfactory treatment options for McArdle disease. Ketones are feasible fuel alternatives to muscle glycogen when muscle glycogenolysis is blocked as in McArdle disease. A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for energy metabolism. Ketosis can potentially provide alternative fuel substrates by provision of endogenous ketone bodies (KBs) which are desirable fuels for skeletal muscle and brain. Ketosis can be reached by fasting and can be induced by adhering to a modified ketogenic diet, which entails a high-fat, low-carbohydrate diet, which simulates the metabolic effects of fasting.
The study design is a placebo-controlled, blind, cross over design. The study will be carried out at two sites: CNMC (Copenhagen), NHNN (London). Subjects will be randomized 1:1 to receive either a modified ketogenic diet (75% fat, 15%protein, 10% carbohydrates) or a placebo diet (>100grams of carbohydrates per day) first. Subjects will follow the diet for 4 weeks, followed by 2-4 weeks wash-out, followed by 4 weeks on the opposite diet. During the 10-12 weeks trial period, subjects will visit the trial site in London on five occasions. Effects of the diet will be evaluated by improvement in exercise capacity during submaximal exercise test on a cycle ergometer. Subjective improvements will be evaluated by questionnaires and a dietary diary.
If the diet improves exercise capacity, it will provide a safe and cheap treatment option that may lead to reduced risk of muscle injury and enhance quality of life in patients with McArdle disease.
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
- Double (Participant, Investigator)
盲法说明
Disguise products (Oral supplements: Nutricia 'ketocal' (intervention) or Nutricia 'fortini' (placebo)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed GSDV
- •Patient is willing and able to provide written informed consent prior to participation.
- •Patient is ambulatory.
- •Women in fertile age must be willing to practice the following medically acceptable methods of birth control
排除标准
- •Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements.
- •Pregnancy or breastfeeding
- •Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments
- •Patients with porphyria or disorders of fat metabolism (primary carnitine deficiency, carnitine palmitoyltransferase I or II, β-oxidation defects etc.).
结局指标
主要结局
Change in mean heart rate
时间窗: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in mean heart rate (bpm) during constant load cycling exercise (30 minute submaximal cycle test). Heart rate will be measured every minute during the cycle test at all visits.
次要结局
- Change in blood ketones(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in ammonia(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in free fatty acids(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in glucose(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in Indirect calorimetry(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in self-rated fatigue(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in self-rated daily function scores(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in perceived exertion(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in insulin(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in maximal oxygen capacity(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in maximal work load(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Compliance(up 12 weeks)
- Change in glucagon(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in Adrenalin(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
- Change in lactate(At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks))
研究者
Nicoline Løkken
MD, Research fellow
Rigshospitalet, Denmark