Clinical trial NCT00481429: Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study
Official title: Evaluation of Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Diabetes Mellitus, Type 2
Keywords: Biomarker
Glitazone
Diabetes
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2007-06-01
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with type 2 diabetes attending clinic

Brief summary: 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:

1. Do baseline measurements of a selected panel of biomarkers predict the patients' response to rosiglitazone over 12 weeks?
2. How does the panel of biomarkers change over that 12 week treatment period?

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Male subjects aged 18 to 65 years.
2. 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.
3. BMI must be \> or = 25kg/m2 to \< or = 40kg/m2,
4. HbA1c between 7and 10%, fasting blood glucose above 7mmol/L (fasting means greater or = 8 hours prior to screening).
5. 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.
6. On stable doses of anti-hypertensive medication, thyroid hormone replacement and statin therapy as required.

Exclusion Criteria:

1. Prior treatment with thiazolidinedione, insulin or GLP-1 analogue (Byetta)
2. 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.
3. Contraindications to rosiglitazone treatment.
4. Serum creatinine greater than 1.5 X upper limit of normal range.
5. Any other clinically significant laboratory abnormality.
6. Claustrophobic or other contraindication to MRI scan
7. Females of child-bearing age who are unwilling to use appropriate methods of contraception.
8. Unable to give informed consent.
9. Unable to comply with study protocol.
10. Clinically significant co-morbidity. -

Primary outcomes:
measure: 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.
timeFrame: 12 weeks
Secondary outcomes:
measure: Variability in baseline levels of key biochemical markers in diabetic patients.
timeFrame: 12 weeks
measure: Effect of treatment on a variety of other novel potential predictive biomarkers and markers of insulin sensitisation in diabetic patients.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Ealing Hospital
city: London
country: United Kingdom
facility: Imperial College London - Hammersmith Campus
city: London
country: United Kingdom
facility: Charing Cross Hospital
Study officials:
affiliation: Imperial College London
name: Martin R Wilkins, MD FRCP
role: PRINCIPAL_INVESTIGATOR
References: