Response To Oral Agents in Diabetes (ROAD)- Pilot Study
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetes Mellitus, Type 2 |
Drug: Gliclazide MR Drug: Sitagliptin Drug: Pioglitazone Drug: Metformin |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Response To Oral Agents in Diabetes (ROAD)- Pilot Study |
- HbA1c reduction [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Time to treatment failure [ Time Frame: 10 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | December 2008 |
| Estimated Study Completion Date: | October 2009 |
| Estimated Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: Gliclazide MR |
Drug: Gliclazide MR
30mg daily increased to 60mg if HbA1c > 7% at 3 months
Other Name: Diamicon MR
|
| Active Comparator: Sitagliptin |
Drug: Sitagliptin
Sitagliptin 100mg daily for 6 months
|
| Active Comparator: Pioglitazone |
Drug: Pioglitazone
Pioglitazone 30mg daily , increased to 45mg daily if HbA1c >7% at 3 months. 6 months duration
Other Name: Actos
|
| Experimental: Metformin |
Drug: Metformin
Metformin 500 mg od for 1 week, bd for 1 week, 1g mane 500 mg nocte 1 week, 1g bd there after. Total of 6 months treatment
|
Detailed Description:
The Response to Oral Agents in Diabetes (ROAD) study aims to address the limitations of observational data by creating a prospective study of incident users of oral agents. For the first six months the research team will ensure a protocol driven dose titration, standardised monitoring of adherence, response and side effects and standardised deviations from therapy. Thereafter patients will receive 6 monthly monitoring and further protocol led dose titration by the GP. Biochemistry, prescribing data, morbidity and mortality data will be captured for up to 10 years from drug initiation. The ROAD study will provide a highly powered prospective cohort to investigate phenotypic and genotypic determinants of response in its own right. However, this cohort will be used synergistically with ongoing observational pharmacogenetics studies, allowing for crucial replication of 'positive' signals. Furthermore, by randomisation at drug initiation, long term community follow up will allow a comparison of time to treatment failure in patients treated with gliclazide, pioglitazone and sitagliptin in a much more cost effective and 'real-world' setting than traditional prospective randomised trials This pilot study is to assess the feasibility of the larger complex intervention, particularly optimising the patient recruitment process, questionnaires, dose titration and monitoring, and randomisation to different second line agents. With knowledge from this pilot, an application will be made for a large region or Scotland wide study to collect 2000 patients incident to oral diabetes treatment.
Eligibility| Ages Eligible for Study: | 36 Years to 79 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations More Information
No publications provided
| Responsible Party: | Ewan Pearson/Senior Lecturer, University of Dundee |
| ClinicalTrials.gov Identifier: | NCT00780715 History of Changes |
| Other Study ID Numbers: | 2008DM05, EudraCT 2008-004790-18 |
| Study First Received: | October 27, 2008 |
| Last Updated: | December 24, 2008 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by University of Dundee:
|
Diabetes therapies Pharmacogenetics |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Pioglitazone Sitagliptin Gliclazide |
Metformin Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 18, 2013