Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study

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

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?

Study Overview

• Status: Withdrawn
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Rosiglitazone

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 2GG
    • Addenbrooke's Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, UB1 3HW
    • Ealing Hospital
  • London, United Kingdom, W12 ONN
    • Imperial College London - Hammersmith Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes attending clinic

Description

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. -

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Rosiglitazone	Drug: Rosiglitazone; Rosiglitazone 4mg od, increased to 4mg bg at 4 weeks if HbA1C above 7%.
2; Diet control +/- metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Martin R Wilkins, MD FRCP, Imperial College London

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2007
• Primary Completion (ANTICIPATED): January 1, 2008
• Study Completion (ANTICIPATED): January 1, 2008

Study Registration Dates

• First Submitted: May 31, 2007
• First Submitted That Met QC Criteria: May 31, 2007
• First Posted (ESTIMATE): June 1, 2007

Study Record Updates

• Last Update Posted (ACTUAL): July 10, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Biomarker; Diabetes; Glitazone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Rosiglitazone
• Other Study ID Numbers: cro700

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO