The use of glycaemic response to sulphonylureas as a tool to investigate Type 2 diabetes pathophysiology - Variation in sulphonylurea response in Type 2 diabetes

Phase 1

• Conditions: Type 2 diabetes; MedDRA version: 9.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus

• Registration Number: EUCTR2007-000594-29-GB
• Lead Sponsor: HS Tayside

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-26
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Study 1.
•Type 2 diabetes
•Age >35 and < 70
•Age of diabetes diagnosis >35 and <70
•White European
•Pre-SU HbA1c <=10%
•HbA1c (on treatment) <= 9%
•No established cardiovascular disease (previous established angina or myocardial infarction)
•No established cerebrovascular disease (previous stroke or transient ischaemic attack)
•No or stable (background) retinopathy (no unscheduled laser treatment in the last 6 months)
•eGFR > 60mls/min
•No frank proteinuria (on multistix 10SG)
•No active foot ulceration or infection
•Liver ALT within the laboratory reference range
•Contactable by telephone

Study 2.

•Age >35 and < 70
•Age of diabetes diagnosis >35 and <70
•White European
•HbA1c = 7% and = 9%
•Not on SU and no previous SU intolerance
•No established cardiovascular disease (previous established angina or myocardial infarction)
•No established cerebrovascular disease (previous stroke or transient ischaemic attack)
•No or stable (background) retinopathy (no unscheduled laser treatment in the last 6 months)
•eGFR > 60 ml/min
•No frank proteinuria (on multistix 10SG)
•No active foot ulceration or infection
•Liver ALT within the laboratory reference range
•Contactable by telephone

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Type 1 diabetes
•HbA1c >10% prior to commencing SU
•HbA1c>9% on SU treatment
Study 1
•Previous cardiovascular or cerebrovascular disease
•Pre-proliferative or proliferative retinopathy
•eGFR<60 ml/min
•Proteinuria (multistix 10 SG)
•Active foot ulceration or infection
•Liver ALT outwith the reference range
•Female planning to conceive within the study period
•Any other significant medical reason for exclusion as determined by the investigator

Study 2

•Type 1 diabetes
•HbA1c = 7% or = 9%.
•Previous cardiovascular or cerebrovascular disease
•Pre-proliferative or proliferative retinopathy
•eGFR< 60 ml/min
•Proteinuria (multistix 10 SG)
•Active foot ulceration or infection
•Liver ALT outwith the reference range
•Female planning to conceive within the study period
•Any other significant medical reason for exclusion as determined by the investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To define phenotypic differences that predict sulphonylurea response in order to identify aetiological differences in these distinct subgroups, by intensively studying:<br>i. Beta cell response to intravenous glucose and tolbutamide to identify quantitative and qualitative differences in function<br>ii. Insulin sensitivity<br>iii. Pharmacokinetics<br>;Secondary Objective: a) To establish a cohort of patients who are adherent to sulphonylurea therapy, but whose response is either good or poor.<br>b) To validate the initial determination of response from the database by correlation with a controlled re-challenge response, to allow future large-scale pharmacogenetics studies<br>c) To investigate whether patients GG homozygous at rs12255372 of TCF7L2 respond better to sulphonylureas than those who are TT homozygous at this SNP<br>;Primary end point(s): Study 1 and 2.<br><br>Change in HbA1c