Clinical trial NCT02533648: Role of Allopurinol on Oxidative Stress and Mitochondrial Alterations in Skeletal Muscle of Diabetic Patients
Official title: Involvement of Reactive Oxygen Species Produced by the Xanthine Oxidase in Mitochondrial Alterations in Skeletal Muscle of Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes mellitus, oxidative stress
insulin sensitivity
insulin resistance
mitochondrial dysfunction
skeletal muscle
xanthine oxidase
allopurinol
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2015-08-27
Enrollment: 31
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: muscle oxidative stress in diabetic patients
timeFrame: At 3 months of treatment
Secondary outcomes:
measure: - plasmatic oxidative stress by dosing plasmaticmarkers:
timeFrame: At 3 months of treatment
measure: alterations in mitochondrial structure of skeletal muscle with transmission electron microscopy
timeFrame: At 3 months of treatment
measure: mitochondrial density by measuring the ratio mitochondrial Deoxyribonucleic acid (mtDNA)/nuclear DNA by real-time polymerase chain reaction (PCR) in skeletal muscle
timeFrame: At 3 months of treatment
measure: mitochondrial function
timeFrame: At 3 months of treatment
measure: quantification of intramuscular lipids by histology (biopsy analysis)
timeFrame: At 3 months of treatment
measure: sensitivity to insulin using a hyperinsulinemic euglycemic clamp
timeFrame: At 3 months of treatment
measure: uricemia and xanthine oxidase activity in sera and muscles(unit: mg/l for uricemia and mU/ml for XO activity)
timeFrame: At 3 months of treatment
measure: Tolerance of the treatment measured by any adverse events during treatment and between each visit.
timeFrame: during the 3 months of treatment
Other outcomes:
Locations:
city: Lyon
country: France
facility: CRNH Rhône Alpes
Study officials:
References: