PROMASTER - PROspective Cohort MRC ABPI STratification and Extreme Response Mechanism in Diabetes

Study Overview
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Brief Summary
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This study will examine extreme responders to second- and third-line Type 2 diabetes therapy using a prospective approach, and patients with slow or fast diabetes progression using a retrospective approach.

Detailed Description
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PILOT Phase (March 2013 - Dec 2014) Participants will be recruited initially from 4 centres. Patients due to start second- and third-line Type 2 diabetes treatments, and patients progressing to insulin either particularly quickly or particularly slowly, will be recruited from primary care, secondary care, or community settings. Fasting blood and urine samples will be collected, together with standard biomeasures and information about medical history and prescribing history. Participants in Responders Arm will be contacted by telephone approximately 3 months after starting their new second/third-line agent to review their current medication and blood glucose level. If a 3 month HbA1c has not been collected as part of routine clinical care, the research team will arrange this. Participants will be asked to return for a blood and urine test approximately 6 months after their new treatment was started. This visit will be brought forward should the participant advise they are about to further change their treatment, to enable their samples to be collected in advance of their proposed treatment change. All study documentation and sample materials will be distributed to sites from the Coordinating Centre. Sites will be expected to process and freeze samples and send them to the Chief Investigator's Central Laboratory where they will be analysed for genetic factors, glycaemic markers and other markers related to drug response. POST-PILOT Phase (Jan 2015 - Oct 2017) Subject to feasibility, interim analysis and continuation of funding from Medical Research Council (MRC), this study will continue for another 3 years.

Official Title
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PROspective Cohort MRC ABPI STratification and Extreme Response Mechanism in Diabetes

Conditions
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Diabetes

Intervention / Treatment
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* Drug: second- or third-line glucose-lowering diabetes treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Demographics: Age 18-90 inclusive Ethnicity: Reflective of local demographic Medical History: Clinical diagnosis of Type 2 diabetes Mental Capacity: Capacity to Consent Exclusion Criteria: Age less than 18 years old and greater than 90 years old Incapacity to consent Type 1 diabetes.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Responders<br>Patients with Type 2 diabetes about to commence a second- or third-line glucose-lowering treatment (Sulphonylurea, DPP-4 inhibitors, GLP-1R agonists, SGLT2 inhibitors or Glitazone or insulin). | Drug: second- or third-line glucose-lowering diabetes treatment<br>* Observation of response and disease progression following clinician's addition of a glucose-lowering diabetes therapy (Sulphonylurea, DPP-4 inhibitor, GLP-1R agonist, SGLT2 inhibitor or Glitazone) to existing therapy.<br>* Other names: Glitazone;|
| Progressors<br>Patients with Type 2 diabetes that progress to requiring insulin treatment ≤10 years from diagnosis or have no requirement for insulin treatment >10 years from diagnosis. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to diabetes therapy | The primary outcome will be to compare the clinical characteristics of the patients who show an excellent response or a poor response to specific second- and third-line classes of treatment for Type 2 diabetes. | Up to 9 months from commencement of new therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collection of samples for analysis of potential biomarkers | To collect a set of DNA, serum and urine samples to allow analysis of potential genetic and non genetic biomarkers for drug response and diabetes progression. | within 9 months of recruitment date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 2 diabetes, Diabetes therapy response, Diabetes progression