Predicting Response to Incretin Based Agents in Type 2 Diabetes

NCT01503112 | Completed

• 1 other identifier: 11233581
• Study Type: observational
• Target: 957
• Locations: 1 country
• Sites: 18

Brief Summary

Type 2 diabetes is a major and rapidly increasing health problem worldwide. Keeping the blood glucose (sugar) from going too high helps prevent complications. Recently a number of new treatments (collectively called 'incretin based' treatments) to lower blood glucose have become available but response is very variable and it is difficult to predict which will work for an individual. The investigators want to see if we can identify whether the new treatments are likely to be effective for an individual patient. Identifying the right treatment would improve control and minimise the side-effects and costs from ineffective treatments. We will collect blood (for measures of blood glucose, insulin secretion and genetics information), urine (for a simple measurement of insulin secretion) and other clinical information (such as weight,age, duration of diabetes and medication) in people who are about to start these new 'incretin based' treatments and assess their response over the first 6 months of treatment. We will analyse this information to see if we can predict treatment response. Study Hypothesis: The investigators hypothesise that those who have low insulin secretion, as measured by post meal urine C-peptide Creatinine Ratio or blood C-peptide, will have poor blood glucose response to incretin based treatments.

Conditions

Type2 Diabetes

Keywords

Glucagon-Like Peptide 1, DPP4 protein, Therapeutics, Hypoglycemic Agents, C-Peptide, Type 2 Diabetes Mellitus,

Outcome Measures

Primary Outcomes (1)

• Glycaemic response (HbA1c change post treatment)

  Change in HbA1c over 6 months treatment (as a continuous variable and/or defined as binary response/non response). Our Primary analysis will be the relationship between insulin secretion (as measured by blood C-peptide or UCPCR) and glycaemic response. Secondary analysis will include examination of relationship between baseline weight, HbA1c, age, duration of diabetes, HOMA B, HOMA IR, autoantibody (GAD, IA2) status and glycaemic response. We will also examine the relationship between glycaemic response and polymorphisms in GLP-1R, TCF7L2, WFS1 and FOX01 genes.

  6 months

Secondary Outcomes (1)

• Weight change over 6 months treatment

  6 months

Study Arms (1)

Patients starting incretin treatments

Patients starting GLP-1 agonists or DPPIV inhibitors as part of their normal clinical care.

Other: No intervention, observational study

Interventions

No intervention, observational study OTHER

Patients starting incretin treatments

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 Diabetes commencing DPP-IV inhibitors or GLP-1 agonsists in primary or secondary care in England

You may qualify if:

• A clinical diagnosis of type 2 diabetes mellitus where the patient's clinician has determined the need for a DPP-IV inhibitor or GLP-1 analogue as a result of inadequate glycaemic control
• HbA1c \>= 58mmol/mol

You may not qualify if:

• Treatment with DPP-IV inhibitors or GLP-1 analogues prior to study initiation (within the previous 3 months)
• Renal failure as shown by a eGFR (estimated glomerular filtration rate) less than 30 mL/min/1.73m2

Sponsors & Collaborators

• Royal Devon and Exeter NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator
• University of Exeter: collaborator

Study Sites (18)

Cornwall and Isles of Scilly NHS Primary Care Trust

Truro, Cornwall, TR13HD, United Kingdom

Location

North Devon NHS Trust

Barnstaple, Devon, EX314JB, United Kingdom

Location

Royal Devon and Exeter NHS Foundation Trust

Exeter, Devon, EX25DW, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, Devon, PL68DH, United Kingdom

Location

South Devon Healthcare NHS Foundation Trust

Torbay, Devon, TQ27AA, United Kingdom

Location

Taunton and Somerset NHS Foundation Trust.

Taunton, Somerset, BA228HR, United Kingdom

Location

Yeovil Disctrict Hospital NHS Foundation Trust

Yeovil, Somerset, BA21 4AT, United Kingdom

Location

The Royal Bournmouth and Christchurch Hospitals NHS Trust

Bournmouth, BH7 7DW, United Kingdom

Location

North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

Location

Ipswich Hospital NHS Trust

Ipswich, IP4 5PD, United Kingdom

Location

Northampton General Hospital NHS Trust

Northampton, NN15BD, United Kingdom

Location

Oxford Radcliffe Hospitals NHS Trust

Oxford, OX3 9DU, United Kingdom

Location

Portsmouth Hospitals NHS Trust

Portsmouth, PO6 3LY, United Kingdom

Location

Surrey and Sussex Healthcare NHS trust

Redhill, RH1 5RH, United Kingdom

Location

East Sussex Healthcare NHS Trust

Saint Leonards-on-Sea, TN37 7RD, United Kingdom

Location

University Hospitls North Staffordshire NHS Trust

Stoke-on-Trent, ST4 7LN, United Kingdom

Location

South Warwickshire NHS Foundation Trust

Warwick, CV34 5BW, United Kingdom

Location

West Hertfordshire Hospitals NHS Trust

Watford, WD18 0HB, United Kingdom

Location

Related Publications (3)

• Jones AG, McDonald TJ, Shields BM, Hill AV, Hyde CJ, Knight BA, Hattersley AT; PRIBA Study Group. Markers of beta-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes. Diabetes Care. 2016 Feb;39(2):250-7. doi: 10.2337/dc15-0258. Epub 2015 Aug 4.

  PMID: 26242184 RESULT

• Dennis JM, Shields BM, Hill AV, Knight BA, McDonald TJ, Rodgers LR, Weedon MN, Henley WE, Sattar N, Holman RR, Pearson ER, Hattersley AT, Jones AG; MASTERMIND Consortium. Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy. Diabetes Care. 2018 Apr;41(4):705-712. doi: 10.2337/dc17-1827. Epub 2018 Jan 31.

  PMID: 29386249 RESULT

• Jones AG, Shields BM, Hyde CJ, Henley WE, Hattersley AT. Identifying good responders to glucose lowering therapy in type 2 diabetes: implications for stratified medicine. PLoS One. 2014 Oct 23;9(10):e111235. doi: 10.1371/journal.pone.0111235. eCollection 2014.

  PMID: 25340784 RESULT

Related Links

• Research group website

Biospecimen

Retention: SAMPLES WITH DNA

Extracted DNA, stored serum/plasma

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Observation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Andrew T Hattersley

  University of Exeter Medical School/Royal Devon and Exeter Hospital NHS Foundation Trust

  STUDY DIRECTOR

• Angus Jones

  University of Exeter Medical School/Royal Devon and Exeter Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: NIHR Doctoral Research Fellow

Study Record Dates

• First Submitted: December 30, 2011
• First Posted: January 2, 2012
• Study Start: May 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 19, 2018

Record last verified: 2018-04

Locations

GB (18)