Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00481429
First received: May 31, 2007
Last updated: January 28, 2009
Last verified: May 2007
  Purpose

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?

Condition Intervention
Diabetes Mellitus, Type 2
Drug: Rosiglitazone

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Evaluation of Predictive Markers of Glitazone Efficacy in Diabetic Patients - Pilot Study

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • 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. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Variability in baseline levels of key biochemical markers in diabetic patients. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Effect of treatment on a variety of other novel potential predictive biomarkers and markers of insulin sensitisation in diabetic patients. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: May 2007
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Rosiglitazone
Drug: Rosiglitazone
Rosiglitazone 4mg od, increased to 4mg bg at 4 weeks if HbA1C above 7%.
No Intervention: 2
Diet control +/- metformin

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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. -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481429

Locations
United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 2GG
Imperial College London - Hammersmith Campus
London, United Kingdom, W12 ONN
Ealing Hospital
London, United Kingdom, UB1 3HW
Charing Cross Hospital
London, United Kingdom, W6 8RF
Sponsors and Collaborators
Imperial College London
GlaxoSmithKline
Investigators
Principal Investigator: Martin R Wilkins, MD FRCP Imperial College London
  More Information

No publications provided

Responsible Party: Martin R Wilkins, MD FRCP, Imperial College London
ClinicalTrials.gov Identifier: NCT00481429     History of Changes
Other Study ID Numbers: cro700
Study First Received: May 31, 2007
Last Updated: January 28, 2009
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Biomarker
Glitazone
Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014