Glucose Response, Excursions And Treatment (GREAT) Study

NCT02506296 | Completed

• 1 other identifier: R&D no 1503059
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with type 2 diabetes have very variable endogenous insulin secretion. While some patients have relatively preserved endogenous insulin with marked insulin resistance others may develop the very severe insulin deficiency seen in type 1 diabetes. The impact of this variation on hypoglycaemia risk and treatment response in type 2 diabetes is unclear. This project aims to determine the impact of residual endogenous insulin secretion on glucose variability, hypoglycaemia risk and treatment response in insulin-treated participants with a clinical diagnosis of type 2 diabetes. The investigators will recruit participants from existing cohorts known to have severe insulin deficiency despite classical clinical characteristics of type 2 diabetes. The investigators will recruit other participants with insulin-treated type 2 diabetes and retained endogenous insulin secretion matched for glycemia and gender. The investigators will assess glucose variability (using continuous glucose monitoring system (CGMS)) and treatment response to a single dose of the glucose lowering therapy vildagliptin and compare responses between groups. This study will allow us to assess the potential utility of measuring endogenous insulin secretion in insulin-treated type 2 diabetes as a marker of hypoglycaemia risk and in determining likely response to oral therapy.

Conditions

Type 2 Diabetes

Keywords

type 2 diabetes; endogenous insulin secretion

Outcome Measures

Primary Outcomes (2)

• difference in glucose variability

  defined by mean average glucose excursions (MAGE) assessed by CGMS between groups.

  over a 4-6 day period

• Difference in response to a standard DPPIV therapy

  change in incremental area under the curve glucose after mixed meal test with vildagliptin vs without vildagliptin) between groups

  During a standardised Mixed meal Tolerance Test blood samples will be taken immediately before and at 30, 60, 90, 120, 150 and 180 minutes following consumption of a meal replacement drink.

Secondary Outcomes (2)

• Differences in hypoglycemia scores

  snapshot covering last 6 months

• differences in time spent in hypoglycaemia

  4-6 days

Study Arms (1)

Insulin treated T2D diagnosed >=35yrs

OTHER

split by presence or absence of severe endogenous insulin deficiency: * Severe deficiency = fasting blood C-peptide ≤0.08nmol/L or stimulated C-peptide ≤0.2nmol/L or post meal urine C-peptide creatinine ratio ≤0.2nmol/mmol * Retained endogenous insulin secretion = fasting blood C-peptide ≥0.25nmol/L or stimulated C-peptide ≥0.6nmol/L or post meal urine C-peptide creatinine ratio ≥0.6nmol/mmol Groups will be compared for: * glucose variability (via Continuous Glucose Monitoring System (CGM)) and hypoglycaemia risk (via hypoglycaemia questionnaire) * glycaemic response to standard DPPIV inhibitor therapy

Drug: DPPIV inhibitor -; Device: Continuous glucose monitoring system.

Interventions

DPPIV inhibitor - DRUG

Mixed Meal Tolerance Test with or without a DPPIV inhibitor

Also known as: Vidagliptin

Insulin treated T2D diagnosed >=35yrs

Continuous glucose monitoring system. DEVICE

participant's will self-monitor blood glucose over a 4-6 day period via a CGM monitor inserted just under the skin.

Also known as: CGM system

Insulin treated T2D diagnosed >=35yrs

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of type 2 diabetes Diagnosis of diabetes ≥ age 35 Treated with insulin Time from diagnosis to requiring insulin therapy of ≥36 months HbA1c ≥53mmol/mol (7%) and ≤100mmol/mol (11.3%)
• Presence or absence of severe endogenous insulin deficiency:
• Severe deficiency = fasting blood C-peptide ≤0.08nmol/L or stimulated C-peptide ≤0.2nmol/L or post meal urine C-peptide creatinine ratio ≤0.2nmol/mmol
• Retained endogenous insulin secretion = fasting blood C-peptide ≥0.25nmol/L or stimulated C-peptide ≥0.6nmol/L or post meal urine C-peptide creatinine ratio ≥0.6nmol/mmol

You may not qualify if:

• Pregnancy or breastfeeding Moderate renal impairment (EGFR\<30 mls/min/1.73m2) Hepatic impairment (ALT \>3 times upper limit of the normal range) Concurrent treatment with GLP-1 receptor analogue or DPPIV inhibitor glucose-lowering therapy.
• Planned changes to glucose lowering therapy during the study duration Unable to self-monitor blood glucose Unable to give informed consent

Sponsors & Collaborators

• Royal Devon and Exeter NHS Foundation Trust: lead
• NIHR Exeter Clinical Research Facility: collaborator

Study Sites (1)

NIHR Exeter Clinical Research Facility

Exeter, Devon, EX1 2TD, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Continuous Glucose Monitoring

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques

Study Officials

• Angus G Jones, PhD

  NIHR Exeter Clinical Research Facility

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: July 23, 2015
• Study Start: October 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 12, 2016

Record last verified: 2016-04

Locations

GB (1)