Response To Oral Agents in Diabetes (ROAD)- Pilot Study

• Status: Completed
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This proposal is to fund a pilot study to assess feasibility and refine methodology for an intended large Scotland wide study on Response to Oral Agents in Diabetes (ROAD). The study will collect cohorts of patients who have carefully controlled standardised dose titration and monitoring with an assessment of drug response and side effects over a 6 month period. The primary aim will be to use these cohorts to investigate phenotypic and genotypic (pharmacogenetic) determinants of response.

Drug naïve patients will be treated with Metformin. Patients who have failed on Metformin or are intolerant of Metformin will be randomised to gliclazide, pioglitazone or sitagliptin. With the ability to capture patient data beyond 6 months via data linkage we will monitor time to treatment failure and therefore compare which of the 3 oral agents is the best therapy to use after Metformin in a cost efficient and "real world" RCT.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Treatments: Gliclazide; Metformin; Pioglitazone; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

• Cohort 1 - metformin treatment

• Type 2 diabetes diagnosed more than 6 weeks prior to visit 1

• GP considers adequate diet and lifestyle advice given

• Age >35 and < 80

• Age of diabetes diagnosis >35

• White European

• HbA1c >7% & <=9%

• eGFR>=50 ml/min

• ALT <= 2.5*ULN

• Contactable by telephone

• Cohort 2 - 2nd line treatment

• Type 2 diabetes

• Treated with metformin for more than 3 months; or metformin intolerant

• Age >35 and < 80

• Age of diabetes diagnosis >35

• White European

• HbA1c >7% & <=9%

• eGFR>=50 ml/min

• ALT <= 2.5*ULN

• No previous history of heart failure; No patients with documented evidence of left ventricular systolic dysfunction OR with symptoms and signs consistent with a clinical diagnosis of heart failure

• No treatment with Gemfibrozil or Rifampicin (CYP2C8 inhibitor or inducer respectively); or with Miconazole or phenylbutazone (increased hypoglycemic effect of gliclazide).

• No diagnosis of osteoporosis

• Contactable by telephone

Exclusion Criteria:

• Cohort 1

• Type 1 diabetes

• HbA1c >9% or <=7%

• eGFR<50 ml/min

• ALT > 2.5*ULN

• Alcohol consumption in excess of 50 units per week

• Pregnancy, lactation or a female planning to conceive within the study period

• Any other significant medical reason for exclusion as determined by the investigator

• Cohort 2

• Type 1 diabetes

• HbA1c >9% or <=7%

• eGFR< 50 ml/min

• ALT > 2.5*ULN

• Previous history of heart failure OR documented evidence of left ventricular systolic dysfunction OR symptoms and signs consistent with a clinical diagnosis of heart failure

• Ongoing treatment with Gemfibrozil or Rifampicin (CYP2C8 inhibitor or inducer respectively); or with Miconazole or phenylbutazone (increased hypoglycemic effect of gliclazide).

• Previous diagnosis of osteoporosis

• Pregnancy, lactation or a female planning to conceive within the study period

• Any other significant medical reason for exclusion as determined by the investigator