Type 2 Diabetes MellitusPhase 3DIAXONCT02533648
Role of Allopurinol on Oxidative Stress and Mitochondrial Alterations in Skeletal Muscle of Diabetic Patients
A Phase 3 study testing 2 capsules of allopurinol 150 mg daily for 3 month and 2 capsules of lactose daily for 3 month in people with Type 2 Diabetes Mellitus, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 60 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- 2 capsules of allopurinol 150 mg daily for 3 month and 2 capsules of lactose daily for 3 month
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteFrance
- Study dates
- 16 Sep 2011to 18 Feb 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Involvement of Reactive Oxygen Species Produced by the Xanthine Oxidase in Mitochondrial Alterations in Skeletal Muscle of Type 2 Diabetic Patients
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.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- 2 capsules of allopurinol 150 mg daily for 3 month, 2 capsules of lactose daily for 3 month
- Keywords
- Type 2 diabetes mellitus, oxidative stress, insulin sensitivity, insulin resistance, mitochondrial dysfunction, skeletal muscle, xanthine oxidase, allopurinol
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance, Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2 capsules of allopurinol 150 mg daily for 3 monthDrug
2 capsules of allopurinol 150 mg daily for 3 month
2 capsules of lactose daily for 3 monthDrug
2 capsules of lactose daily for 3 month
| Study group | Role | What they receive |
|---|---|---|
| Allopurinol | Experimental | Allopurinol, experimental arms, type 2 diabetes subjects receive 2 capsules of allopurinol 150 mg daily for 3 month Receives: Drug: 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 Receives: Drug: 2 capsules of lactose daily for 3 month |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: At 3 months of treatment
Secondary outcomes (8)
- 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)
Measured: At 3 months of treatment
alterations in mitochondrial structure of skeletal muscle with transmission electron microscopy
Analysis of mitochondria area (in µm2) and density (in %)
Measured: 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
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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
Measured: 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.
Measured: during the 3 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2015 (estimated)
- Study start16 Sep 2011
- Primary completionFeb 2016
- Study completion18 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02533648
- Sponsor's protocol ID
- 2010.639
- Acronym
- DIAXO
- Status last verified
- Oct 2019
- First submitted
- 18 May 2015
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Involvement of Reactive Oxygen Species Produced by the Xanthine Oxidase in Mitochondrial Alterations in Skeletal Muscle of Type 2 Diabetic Patients
- ClinicalTrials.gov ID
- NCT02533648
- Acronym / sponsor ID
- DIAXO / 2010.639
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Type 2 diabetes mellitus, oxidative stress, insulin sensitivity, insulin resistance, mitochondrial dysfunction, skeletal muscle, xanthine oxidase, allopurinol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 16 Sep 2011 (actual)
- Primary completion
- Feb 2016 (actual)
- Study completion
- 18 Feb 2016 (actual)
- First posted
- 27 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allopurinol | Experimental | Drug: 2 capsules of allopurinol 150 mg daily for 3 monthAllopurinol, experimental arms, type 2 diabetes subjects receive 2 capsules of allopurinol 150 mg daily for 3 month |
| Placebo | Placebo comparator | Drug: 2 capsules of lactose daily for 3 monthPlacebo, type 2 diabetes subjects receive 2 capsules of lactose (placebo) daily for 3 month |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2 capsules of allopurinol 150 mg daily for 3 month2 capsules of allopurinol 150 mg daily for 3 month | Drug | Allopurinol |
| 2 capsules of lactose daily for 3 month2 capsules of lactose daily for 3 month | Drug | Placebo |
Primary outcome
muscle oxidative stress in diabetic patients
Time frame: 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)
8 secondary outcomes
- plasmatic oxidative stress by dosing plasmaticmarkers:
Time frame: At 3 months of treatment
alterations in mitochondrial structure of skeletal muscle with transmission electron microscopy
Time frame: 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
Time frame: At 3 months of treatment
mitochondrial function
Time frame: At 3 months of treatment
quantification of intramuscular lipids by histology (biopsy analysis)
Time frame: At 3 months of treatment
sensitivity to insulin using a hyperinsulinemic euglycemic clamp
Time frame: 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)
Time frame: At 3 months of treatment
Tolerance of the treatment measured by any adverse events during treatment and between each visit.
Time frame: during the 3 months of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 2 capsules of allopurinol 150 mg daily for 3 month and 2 capsules of lactose daily for 3 month in people with Type 2 Diabetes Mellitus, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
muscle oxidative stress in diabetic patients (time frame: At 3 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.