RetroMASTER - Retrospective Cohort MRC ABPI STratification and Extreme Response Mechanism in Diabetes (RetroMASTER)

Retrospective Cohort MRC ABPI STratification and Extreme Response Mechanism in Diabetes:

This study will examine extreme responders to second- and third-line Type 2 Diabetes (T2D) therapy using a retrospective approach and patients with slow or fast diabetes progression.

Study Overview

• Status: Completed
• Conditions: Diabetes

Detailed Description

PILOT Phase (March 2013 - Dec 2014) Patients will be recruited initially from 2 centres, plus Exeter as a pre-PILOT centre. Patients with particularly good or poor response to second- and third-line Type 2 diabetes treatments and patients progressing to insulin either particularly quickly or particularly slowly will be recruited from primary, secondary, or community settings. Fasting blood and urine samples will be collected, along with standard biomeasures and information will be collected about medical history and prescribing history.

All study documentation and sample materials will be sent out to sites from the coordinating centre. Sites will be expected to process and freeze samples and send them to the Central Laboratory managed by the Chief Inspector's site 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 project will continue for another three years.

• Study Type: Observational
• Enrollment (Actual): 562

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • University of Dundee
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • University of Exeter
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX1 2JD
      • University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified in primary care and secondary care. The method for patient identification may differ between sites and could involve:

GP Searches; Secondary Care Clinician Referral; Research Database Searches.

Description

Generic 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

Responders Cohort Inclusion Criteria:

• On Sulphonylurea, DPP-4 inhibitor, GLP-1R agonist, SGLT2 inhibitor or Glitazone for > 4 months.
• Pre-treatment HbA1c≥ 58mmol/mol (7.5%).

Progressors Cohort Inclusion Criteria:

• Type 2 diabetes (not on insulin treatment within 6 months of diagnosis)
• Either: requirement for insulin treatment ≤10 years from diagnosis (defined as insulin treatment or HbA1c ≥ 69mmol/mol (8/5%) treated with two or more non-insulin diabetes therapies) or: no requirement for insulin treatment >10 years from diagnosis (defined as not on insulin treatment AND HbA1c <69mmol/mol (8.5%).

Exclusion Criteria:

• Age less than 18 years old and greater than 90 years old
• Incapacity to consent
• Type 1 diabetes.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Responders; Patients with Type 2 diabetes that have been taking a second- or third-line glucose-lowering treatment (Sulphonylurea, DPP-4 inhibitors, GLP-1R agonists, SGLT2 inhibitors, Glitazone or insulin) for at least 4 months.
Progressors; Patients with Type 2 diabetes that progressed to requiring insulin treatment ≤10 years from diagnosis or have had no requirement for insulin treatment >10 years from diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to diabetes therapy and rate of diabetes progression	The primary outcome will be to compare the clinical characteristics of the patients who show an excellent response or poor response to specific second- and third- line classes of treatment for Type 2 diabetes; and of those patients that show rapid progression of Type 2 diabetes or slow progression of Type 2 diabetes to markedly high blood glucose despite the treatment that they require.	Within 9 months from date of recruitment

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

Collaborators and Investigators

• Sponsor: Royal Devon and Exeter NHS Foundation Trust
• Collaborators: University of Oxford; NHS Tayside; Oxford University Hospitals NHS Trust; University of Dundee; University of Exeter

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 9, 2014
• First Posted (Estimate): April 10, 2014

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

• Keywords: Diabetes; Type 2 diabetes; Diabetes therapy response; Diabetes progression
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: CRF117; 12/SW/0348 (Other Identifier: Research Ethics Committee)