Clinical trial NCT01503112: Predicting Response to Incretin Based Agents in Type 2 Diabetes
Official title: Does Urinary C-peptide Creatinine Ratio Predict Response to Incretin Based Agents in Type 2 Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type2 Diabetes
Keywords: Glucagon-Like Peptide 1, DPP4 protein, Therapeutics, Hypoglycemic Agents, C-Peptide, Type 2 Diabetes Mellitus,
Lead sponsor: Royal Devon and Exeter NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: University of Exeter
First posted: 2012-01-02
Enrollment: 957
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Glycaemic response (HbA1c change post treatment)
timeFrame: 6 months
Secondary outcomes:
measure: Weight change over 6 months treatment
timeFrame: 6 months
Other outcomes:
Locations:
city: Truro
country: United Kingdom
facility: Cornwall and Isles of Scilly NHS Primary Care Trust
state: Cornwall
city: Barnstaple
country: United Kingdom
facility: North Devon NHS Trust
state: Devon
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust
state: Devon
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
state: Devon
city: Torbay
country: United Kingdom
facility: South Devon Healthcare NHS Foundation Trust
state: Devon
city: Taunton
country: United Kingdom
facility: Taunton and Somerset NHS Foundation Trust.
state: Somerset
city: Yeovil
country: United Kingdom
facility: Yeovil Disctrict Hospital NHS Foundation Trust
state: Somerset
city: Bournmouth
country: United Kingdom
facility: The Royal Bournmouth and Christchurch Hospitals NHS Trust
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospitals NHS Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
city: Redhill
country: United Kingdom
facility: Surrey and Sussex Healthcare NHS trust
city: St Leonards-on-Sea
country: United Kingdom
facility: East Sussex Healthcare NHS Trust
city: Stoke on Trent
country: United Kingdom
facility: University Hospitls North Staffordshire NHS Trust
city: Warwick
country: United Kingdom
facility: South Warwickshire NHS Foundation Trust
city: Watford
country: United Kingdom
facility: West Hertfordshire Hospitals NHS Trust
Study officials:
affiliation: University of Exeter Medical School/Royal Devon and Exeter Hospital NHS Foundation Trust
name: Andrew T Hattersley
role: STUDY_DIRECTOR
affiliation: University of Exeter Medical School/Royal Devon and Exeter Hospital NHS Foundation Trust
name: Angus Jones
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.