Pharmacological Treatment of a Rare Genetic Disease: Pilot Trial Phase II-III With N-acetylcysteine in Myopathy Associated SEPN1-RM (Selenoprotein N-related Myopathy)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes.
研究概览
简要总结
The objective of this study is to determine whether the administration of N-acetylcysteine (NAC) improves oxidative stress. To determine this, the study will assess the impact of oral treatment on the balance between reduced and oxidized form of glutathione in erythrocytes of peripheral blood.
详细描述
A prospective, monocentric, crossover, double-blind, placebo-controlled study.
For each patient the study will be divided in two treatment periods of 6 months separated by a 2 month washout period. 24 patients will be randomized in two groups, one group treated first with placebo during 6 months, followed by 6 months; the second group treated in the reverse sequence, then placebo.
24 healthy volunteers will also be enrolled in the study in order to collect reference values for biochemical biomarkers.
D-1: run-up visit, patients will be hospitalized in intensive care unit to collect information about diet, physical activity and smoking.
During follow-up visits: we will analyze the impact of treatment with N-acetylcysteine (NAC) on:
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)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For patients:
- •Patient >18 and <60 years old
- •Patients with Selenoprotein N-related myopathy with homozygous or compound heterozygous mutations in the gene SEPN1-RM
- •Informed written consent
- •Patients capable of being followed up throughout the duration of the study
- •Patient trained in the use of cough assist
- •Patients having an health insurance
- •Patient accepting to commit not to introduce major changes in diet and lifestyle during the study period
- •For healthy volunteers:
- •volunteers >18 and <60 years old
- •Informed written consent
- •Health insurance
排除标准
- •For patients:
- •Pregnancy
- •Intolerance to N-acetylcysteine (NAC), galactose or fructose; malabsorption glucose or galactose; lactase deficiency
- •Consumption of synthetic vitamins, NAC and other antioxidants within 3 months prior to inclusion
- •Treatment with corticosteroids or non-steroidal anti-inflammatory from time to time in the 4 weeks preceding the inclusion or for more than 3 days between 12 and 4 weeks before inclusion
- •Planned surgery within 3 months before inclusion or during the inclusion period
- •Intercurrent or existing illnesses such as chronic infectious diseases (HIV, hepatitis, etc.), asthma, malignant tumor pathology, Hematological Pathology
- •Expected survival less than 14 months
- •Inability to understand the instructions or the implications of the Protocol
- •For healthy volunteers:
- •Pregnancy
- •Consumption of synthetic vitamins, NAC and other antioxidants within 3 months prior to inclusion
- •Treatment with corticosteroids or non-steroidal anti-inflammatory from time to time in the 4 weeks preceding the inclusion or for more than 3 days between 12 and 4 weeks before inclusion
- •Planned surgery within 3 months before inclusion or during the inclusion period
- •Intercurrent or existing illnesses such as chronic infectious diseases (HIV, hepatitis, etc.), asthma, malignant tumor pathology, Hematological Pathology
- •Inability to understand the instructions or the implications of the Protocol
- •Bleeding disorders or other bleeding risks or risk of infection.
研究组 & 干预措施
Placebo followed by N-Acetylcysteine
Arm receiving placebo for 6 months, then N-Acetylcysteine (NAC) for 6 months.
干预措施: Placebo followed by N-Acetylcysteine (Drug)
N-Acetylcysteine followed by Placebo
Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.
干预措施: N-Acetylcysteine followed by Placebo (Drug)
结局指标
主要结局
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes.
时间窗: 6 months in each period
次要结局
- measure of health status according The 36-Item Short Form Health Survey (SF36)(6 months in each crossover period)
- Running speed measured by the test of 10 m(6 months in each crossover period)
- Measures of motor function according a Motor Function Measure scale (MFM )(6 months in each crossover period)
- Measurement of the maximum voluntary contraction of the quadriceps(6 months in each crossover period)
- The measurement of the endurance of the quadriceps(6 months in each crossover period)
- Evaluate the impact of fatigue according the Fatigue Severity Scale (FSS)(6 months in each crossover period)
- Measure of Activity Limitation (Activlim test)(6 months in each crossover period)
- Muscular endurance is measured by the test of 2 minutes walk(6 months in each crossover period)
- Measurement of biomarkers in blood samples, muscle and fibroblasts(6 months in each crossover period)
- Assessment of dyspnea according Borg scale(6 months in each crossover period)