Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study

Study Overview
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Brief Summary
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Hypothesis: A cluster of biochemical measurements (biomarkers) predict which diabetic patients will respond to treatment with a therapeutic dose of rosiglitazone over a 12 week treatment period. Brief Summary: The purpose of this study is to assess the predictive value of the biomarkers in diabetic patients treated with a full dose of a thiazolidinedione (eg 4mg bid rosiglitazone) for 12 weeks. Specifically - the questions asked are: Do baseline measurements of a selected panel of biomarkers predict the patients' response to rosiglitazone over 12 weeks? How does the panel of biomarkers change over that 12 week treatment period?

Detailed Description
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Rosiglitazone (Avandia) is a medicine used to treat type 2 diabetes. It works by increasing the sensitivity of body tissues to insulin. This pilot study will examine the possibility that baseline biochemistry might predict the response to rosiglitazone. The study will be conducted in males and the biomarkers of interest measured by specific assays. In addition, since the biomarkers to be measured come from body fat, interpretation of the data would be facilitated by accurate measurements of changes in body fat mass during treatment and these data can be obtained from Echo-MRI scans.

Official Title
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Evaluation of Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Rosiglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects aged 18 to 65 years. Eligible subjects must be free from clinically significant illness or disease (other than type 2 diabetes)with the exception of chronic stable-treated hypertension (BP<160/90, and >90/50), thyroid disease (TSH in the normal reference range) and/or dyslipidaemia. BMI must be > or = 25kg/m2 to < or = 40kg/m2, HbA1c between 7and 10%, fasting blood glucose above 7mmol/L (fasting means greater or = 8 hours prior to screening). On diet alone or diet plus metformin (GSK data indicate that the latter group more faithfully reflect the behaviour of 'naive' patients than those who have been washed off prior medications)for at least 1 month. On stable doses of anti-hypertensive medication, thyroid hormone replacement and statin therapy as required. Exclusion Criteria: Prior treatment with thiazolidinedione, insulin or GLP-1 analogue (Byetta) History of hepatic disease, impairment or abnormal liver function test i.e. AST, ALT>2 times upper limit of normal range (ULN), bilirubin>1.5 time ULN. History of renal disease or serum creatinine greater than 1.5 X ULN. Contraindications to rosiglitazone treatment. Serum creatinine greater than 1.5 X upper limit of normal range. Any other clinically significant laboratory abnormality. Claustrophobic or other contraindication to MRI scan Females of child-bearing age who are unwilling to use appropriate methods of contraception. Unable to give informed consent. Unable to comply with study protocol. Clinically significant co-morbidity. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Rosiglitazone | Drug: Rosiglitazone<br>* Rosiglitazone 4mg od, increased to 4mg bg at 4 weeks if HbA1C above 7%.<br>|
| 2<br>Diet control +/- metformin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The performance of baseline biochemical biomarkers in plasma and urine in distinguishing patients who respond to rosiglitazone from those that do not, as classified by a change in HbA1C at 12 weeks. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variability in baseline levels of key biochemical markers in diabetic patients. |  | 12 weeks | 
| Effect of treatment on a variety of other novel potential predictive biomarkers and markers of insulin sensitisation in diabetic patients. |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarker, Glitazone, Diabetes