PROMASTER - PROspective Cohort MRC ABPI STratification and Extreme Response Mechanism in Diabetes (PROMASTER)

PROspective Cohort MRC ABPI STratification and Extreme Response Mechanism in Diabetes

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

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: second- or third-line glucose-lowering diabetes treatment

Detailed Description

PILOT Phase (March 2013 - Dec 2014) Participants will be recruited initially from 4 centres. Patients due to start second- and third-line Type 2 diabetes treatments, and patients progressing to insulin either particularly quickly or particularly slowly, will be recruited from primary care, secondary care, or community settings. Fasting blood and urine samples will be collected, together with standard biomeasures and information about medical history and prescribing history. Participants in Responders Arm will be contacted by telephone approximately 3 months after starting their new second/third-line agent to review their current medication and blood glucose level. If a 3 month HbA1c has not been collected as part of routine clinical care, the research team will arrange this. Participants will be asked to return for a blood and urine test approximately 6 months after their new treatment was started. This visit will be brought forward should the participant advise they are about to further change their treatment, to enable their samples to be collected in advance of their proposed treatment change.

All study documentation and sample materials will be distributed to sites from the Coordinating Centre. Sites will be expected to process and freeze samples and send them to the Chief Investigator's Central Laboratory 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 study will continue for another 3 years.

• Study Type: Observational
• Enrollment (Actual): 820

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G12 8TA
    • University of Glasgow
  • London, United Kingdom, SE1 9NH
    • King's College University of London
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • University of Exeter
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Oxford University Hospitals NHS Trust
  • Tyne And Wear
    • Newcastle upon Tyne, Tyne And Wear, United Kingdom, NE1 7RU
      • University of Newcastle

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

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

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	Intervention / Treatment
Responders; Patients with Type 2 diabetes about to commence a second- or third-line glucose-lowering treatment (Sulphonylurea, DPP-4 inhibitors, GLP-1R agonists, SGLT2 inhibitors or Glitazone or insulin).	Drug: second- or third-line glucose-lowering diabetes treatment; Observation of response and disease progression following clinician's addition of a glucose-lowering diabetes therapy (Sulphonylurea, DPP-4 inhibitor, GLP-1R agonist, SGLT2 inhibitor or Glitazone) to existing therapy.; Other Names: SGLT2 inhibitor; DPP-4 inhibitor; Sulphonylurea; GLP-1R agonist; Glitazone
Progressors; Patients with Type 2 diabetes that progress to requiring insulin treatment ≤10 years from diagnosis or have 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	The primary outcome will be to compare the clinical characteristics of the patients who show an excellent response or a poor response to specific second- and third-line classes of treatment for Type 2 diabetes.	Up to 9 months from commencement of new therapy

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: King's College London; King's College Hospital NHS Trust; Newcastle University; Newcastle-upon-Tyne Hospitals NHS Trust; Oxford University Hospitals NHS Trust; University of Exeter; NHS Greater Glasgow and Clyde; University of Glasgow

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2016

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (ESTIMATE): April 7, 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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: CRF112; 12/SW/0347 (OTHER: Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO