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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2013 by NIHR Exeter Clinical Research Facility
Sponsor:
Collaborator:
University of Exeter
Information provided by (Responsible Party):
NIHR Exeter Clinical Research Facility
ClinicalTrials.gov Identifier:
NCT01847144
First received: March 13, 2013
Last updated: May 3, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Type 2 Diabetes
Drug: Gliclazide 80mg OD
Drug: Sitagliptin 100mg OD
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2

Resource links provided by NLM:


Further study details as provided by NIHR Exeter Clinical Research Facility:

Primary Outcome Measures:
  • Change in fasting glucose [ Time Frame: 4 weeks post treatment change ] [ Designated as safety issue: Yes ]
    Change in fasting glucose from 0 to 4 weeks post treatment change.


Secondary Outcome Measures:
  • Additional changes in biochemical results [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Secondary outcome measures will include change in glycosylated albumin, HbA1c, home glucose day profile and mixed meal area under the curve glucose


Estimated Enrollment: 200
Study Start Date: April 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   19 Years to 79 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01847144

Contacts
Contact: Catherine D Angwin, MSc +44 1392 406813 C.Angwin@exeter.ac.uk
Contact: Gillian C Baker, PhD +44 1392 406791 G.C.Baker@exeter.ac.uk

Locations
United Kingdom
NIHR Exeter Clinical Research Facility, Royal Devon & Exeter NHS Foundation Trust Not yet recruiting
Exeter, Devon, United Kingdom, EX2 5DW
Sub-Investigator: Angus G Jones, MBBS MRCP         
Sponsors and Collaborators
NIHR Exeter Clinical Research Facility
University of Exeter
Investigators
Principal Investigator: Andrew T Hattersley, FRCP, DM, BM University of Exeter
  More Information

No publications provided

Responsible Party: NIHR Exeter Clinical Research Facility
ClinicalTrials.gov Identifier: NCT01847144     History of Changes
Other Study ID Numbers: CRF111, MR/K005707/1
Study First Received: March 13, 2013
Last Updated: May 3, 2013
Health Authority: United Kingdom: Research Ethics Committee

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

ClinicalTrials.gov processed this record on August 28, 2014