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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allopurinol | Experimental | Allopurinol, experimental arms, type 2 diabetes subjects receive 2 capsules of allopurinol 150 mg daily for 3 month |
|
| Placebo | Placebo Comparator | Placebo, type 2 diabetes subjects receive 2 capsules of lactose (placebo) daily for 3 month |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2 capsules of allopurinol 150 mg daily for 3 month | Drug | 2 capsules of allopurinol 150 mg daily for 3 month |
|
| Measure | Description | Time Frame |
|---|---|---|
| muscle oxidative stress in diabetic patients | 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) | At 3 months of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| - plasmatic oxidative stress by dosing plasmaticmarkers: | Dosing plasmatic malondialdéhyde, plasmatic H2O2, protein carbonylation of plasmatic protein and urinary isoprostans, and finally antioxidants (vitamins C and E, glutathione (unit: from µM to M) | At 3 months of treatment |
| alterations in mitochondrial structure of skeletal muscle with transmission electron microscopy |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRNH Rhône Alpes | Lyon | 69310 | France |
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| 2 capsules of lactose daily for 3 month | Drug | 2 capsules of lactose daily for 3 month |
|
Analysis of mitochondria area (in µm2) and density (in %) |
| 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 |
| mitochondrial function | Expression of genes implicated in mitochondrial action (messenger Ribonucleic acid (mRNA) levels by Reverse transcription polymerase chain reaction (RT-PCR) and proteins levels by Western Blot)(unit: arbitrary ratio relative to housekeeping gene/protein). | At 3 months of treatment |
| quantification of intramuscular lipids by histology (biopsy analysis) | Staining Oil Red O evaluate the intramuscular lipid accumulation using the software ImageJ(unit: % of labelling by field). | At 3 months of treatment |
| sensitivity to insulin using a hyperinsulinemic euglycemic clamp | sensitivity to insulin will be expressed as the glucose infusion rate (GIR)/insulinemia ratio. | 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) | Plasma concentrations of uric acid will be measured before and after treatment to assess patient compliance . The reduction of xanthine oxidase activity in serum and muscle protein lysates will be measured using the kit " Amplex Red xanthine / xanthine oxidase assay kit" from Molecular Probes | At 3 months of treatment |
| Tolerance of the treatment measured by any adverse events during treatment and between each visit. | Any adverse events during treatment and between each visit. | during the 3 months of treatment |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007333 | Insulin Resistance |
| D028361 | Mitochondrial Diseases |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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