Involvement of Reactive Oxygen Species Produced by the Xanthine Oxidase in Mitochondrial Alterations in Skeletal Muscle of Type 2 Diabetic Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- muscle oxidative stress in diabetic patients
研究概览
简要总结
Our recent data in mice have demonstrated a key role of xanthine oxidase in hyperglycemia-induced by Reactive oxygen species production, and a preventive role of allopurinol (inhibitor of xanthine oxidase) on the keeping of mitochondria number and structure, in skeletal muscle of diabetic mice. The investigators want to initiate a clinical trial in order to evaluate the efficacy of allopurinol on the improvement of mitochondrial alterations, oxidative capacities and insulin sensitivity, in skeletal muscle of type 2 diabetic patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI from 25 to 40 kg/m²
- •Type 2 diabetes known for over one year but less than 10 years, treated with Oral anti-diabetic drugs or a Glucagon-like peptide-1 (GLP1-analog)
- •well controlled hypertension (untreated or currently treated) with a systolic blood pressure of 95 to 140 mmHg and diastolic blood pressure of 45 to 90 mmHg and heart frequency of 40 to 100 per minute
- •Recent HbA1c < 9 %
- •Uricemia > 300 µmol/l
- •For women : Menopausal or contraception
- •Renal function as defined by glomerular filtration rate (GFR) ≥ 80 mL/min/1.73 m2
排除标准
- •Tobacco ( more than 5 cigarettes)
- •Excessive drinking
- •Known pathology
- •Hypersensitivity to allopurinol
- •Treatment by anticoagulants, allopurinol, regular steroids or Nonsteroidal anti-inflammatory drug (NSAID), fibrate or insulin
研究组 & 干预措施
Allopurinol
Allopurinol, experimental arms, type 2 diabetes subjects receive 2 capsules of allopurinol 150 mg daily for 3 month
干预措施: 2 capsules of allopurinol 150 mg daily for 3 month (Drug)
Placebo
Placebo, type 2 diabetes subjects receive 2 capsules of lactose (placebo) daily for 3 month
干预措施: 2 capsules of lactose daily for 3 month (Drug)
结局指标
主要结局
muscle oxidative stress in diabetic patients
时间窗: At 3 months of treatment
muscular protein carbonylation level (unit: reactive carbonyl derivates, arbitrary unit) by Western blot (oxyblot kit from Chemicon) and pro et antioxidant genes expression (unit: mRNA levels normalized by housekeeping gene, arbitrary ratio) by real time polymerase chain reaction (RT-PCR)
次要结局
- - plasmatic oxidative stress by dosing plasmaticmarkers:(At 3 months of treatment)
- mitochondrial density by measuring the ratio mitochondrial Deoxyribonucleic acid (mtDNA)/nuclear DNA by real-time polymerase chain reaction (PCR) in skeletal muscle(At 3 months of treatment)
- uricemia and xanthine oxidase activity in sera and muscles(unit: mg/l for uricemia and mU/ml for XO activity)(At 3 months of treatment)
- Tolerance of the treatment measured by any adverse events during treatment and between each visit.(during the 3 months of treatment)
- mitochondrial function(At 3 months of treatment)
- quantification of intramuscular lipids by histology (biopsy analysis)(At 3 months of treatment)
- sensitivity to insulin using a hyperinsulinemic euglycemic clamp(At 3 months of treatment)
- alterations in mitochondrial structure of skeletal muscle with transmission electron microscopy(At 3 months of treatment)