MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2 Diabetes

Study Overview
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Brief Summary
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Response to treatment in Type 2 Diabetes is highly variable; the same medicine may have little effect in one person but a large effect in another. Understanding mechanisms of altered response to treatment could aid treatment selection and assist the design of new medications with lower nonresponse rates. This study will examine the physiological mechanisms and potential clinical/biomarker predictors of altered response to sulphonylurea and DPPIV inhibitor glucose lowering medication and answer fundamental methodological questions for the future study of variation in treatment response in Type 2 Diabetes. Participants will withdraw sulphonylurea therapy for up to 2 weeks with assessment of baseline characteristics and glycaemic response. Participants will then enter an optional extension where they receive sulphonylurea or DPPIV inhibitor therapy in crossover fashion.

Detailed Description
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Participants will withdraw sulphonylurea therapy for up to 2 weeks (part 1) followed by an optional cross-over extension (part 2)where they are randomized to 4 weeks of treatment with Gliclazide (DPP-IV thera) or Sitagliptin (sulphonylurea), followed by 4 weeks of the second treatment with a 2 week wash-out period in between. Part 1 will allow assessment of response rates to long standing sulphonylurea treatment in clinical practice and potential predictors of this, as well as whether a very brief period (1 week) of treatment withdrawal is a valid assessment of an individual's response to therapy. Part 2 will allow comparison of the approach in part one with response to the same treatment in a trial setting and will allow assessment on whether response is consistent across therapies with different mechanisms of action.

Official Title
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MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Gliclazide 80mg OD
* Drug: Sitagliptin 100mg OD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 and <80 Clinical diagnosis of Type 2 Diabetes Currently treated with sulphonylurea tablets No change in diabetes treatment (new treatments or dose change) within last 3 months Last HbA1c (taken within last 12 months) of ≥42 mmol/mol and ≤75 mmol/mol (6-9%) Able and willing to monitor home blood glucose Able and willing to give informed consent Exclusion Criteria: Current treatment includes: insulin, GLP-1 agonists, DPP-IV inhibitors, glinides Renal impairment (eGFR <30 ml/min/1.73m2) Active infection (any infection requiring antibiotics at present) Recent (within 3 months) surgery or planned surgery Cardiovascular disease (angina, myocardial infarction, stroke, transient ischemic episode) occurring within the previous 3 months Previous history of pancreatitis Pregnant, breastfeeding or planning a pregnancy over the study period Unable/unwilling to monitor home blood glucose

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gliclazide - Sitagliptin<br>Gliclazide 80mg OD and Sitagliptin 100mg OD | Drug: Gliclazide 80mg OD<br>* Gliclazide 80mg OD (DPP-IV inhibitor) - for 4 weeks duration followed by a 2 week wash-out period.<br>* Other names: DPP-IV inhibitor;|
| Active Comparator: Sitagliptin - Gliclazide<br>Gliclazide 80mg OD and Sitagliptin 100mg OD | Drug: Sitagliptin 100mg OD<br>* Sitagliptin 100mg OD (sulphonylurea)- for 4 weeks duration followed by a 2 week wash-out period.<br>* Other names: sulphonylurea OD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting glucose | Change in fasting glucose from 0 to 4 weeks post treatment change. | 4 weeks post treatment change | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional changes in biochemical results | Secondary outcome measures will include change in glycosylated albumin, HbA1c, home glucose day profile and mixed meal area under the curve glucose | 4 weeks |