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

MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Gliclazide 80mg OD; Drug: Sitagliptin 100mg OD

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 Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • NIHR Exeter Clinical Research Facility, Royal Devon & Exeter NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: sulphonylurea OD

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Royal Devon and Exeter NHS Foundation Trust
• Collaborators: University of Exeter

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: March 13, 2013
• First Submitted That Met QC Criteria: May 3, 2013
• First Posted (ESTIMATE): May 6, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sitagliptin Phosphate; Gliclazide; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: CRF111; MR/K005707/1 (OTHER_GRANT: MRC grant reference)