MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2 Diabetes (Mastermind)

• ClinicalTrials.gov Identifier: NCT01847144
• Recruitment Status: Completed
• First Posted: May 6, 2013
• Last Update Posted: June 21, 2018
• Sponsor: Royal Devon and Exeter NHS Foundation Trust
• Collaborator: University of Exeter
• Information provided by (Responsible Party): Royal Devon and Exeter NHS Foundation Trust

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes	Drug: Gliclazide 80mg OD; Drug: Sitagliptin 100mg OD	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2
• Study Start Date: April 2013
• Actual Primary Completion Date: February 2015
• Actual Study Completion Date: February 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Gliclazide - Sitagliptin; Gliclazide 80mg OD and Sitagliptin 100mg OD	Drug: Gliclazide 80mg OD; Gliclazide 80mg OD (DPP-IV inhibitor) - for 4 weeks duration followed by a 2 week wash-out period.; Other Name: DPP-IV inhibitor
Active Comparator: Sitagliptin - Gliclazide; Gliclazide 80mg OD and Sitagliptin 100mg OD	Drug: Sitagliptin 100mg OD; Sitagliptin 100mg OD (sulphonylurea)- for 4 weeks duration followed by a 2 week wash-out period.; Other Name: sulphonylurea OD

Outcome Measures

Primary Outcome Measures :

1. Change in fasting glucose [ Time Frame: 4 weeks post treatment change ]
   Change in fasting glucose from 0 to 4 weeks post treatment change.

Secondary Outcome Measures :

1. Additional changes in biochemical results [ Time Frame: 4 weeks ]
   Secondary outcome measures will include change in glycosylated albumin, HbA1c, home glucose day profile and mixed meal area under the curve glucose

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United Kingdom

NIHR Exeter Clinical Research Facility, Royal Devon & Exeter NHS Foundation Trust

Exeter, Devon, United Kingdom, EX2 5DW

Sponsors and Collaborators

Royal Devon and Exeter NHS Foundation Trust

University of Exeter

Investigators

• Principal Investigator: Andrew T Hattersley, FRCP, DM, BM; University of Exeter

More Information

• Responsible Party: Royal Devon and Exeter NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT01847144 History of Changes
• Other Study ID Numbers: CRF111; MR/K005707/1 ( Other Grant/Funding Number: MRC grant reference )
• First Posted: May 6, 2013
• Last Update Posted: June 21, 2018
• Last Verified: June 2018

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Gliclazide; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action