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

Sponsored by:	University of Dundee
Information provided by:	University of Dundee
ClinicalTrials.gov Identifier:	NCT00780715

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 IV

MedlinePlus related topics: Diabetes

Drug Information available for: Pioglitazone Pioglitazone hydrochloride Metformin Metformin hydrochloride Sitagliptin phosphate Sitagliptin Gliclazide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Response To Oral Agents in Diabetes (ROAD)- Pilot Study

Further study details as provided by University of Dundee:

Primary Outcome Measures:

HbA1c reduction [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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
Gliclazide MR: Active Comparator	Drug: Gliclazide MR 30mg daily increased to 60mg if HbA1c > 7% at 3 months
Sitagliptin: Active Comparator	Drug: Sitagliptin Sitagliptin 100mg daily for 6 months
Pioglitazone: Active Comparator	Drug: Pioglitazone Pioglitazone 30mg daily , increased to 45mg daily if HbA1c >7% at 3 months. 6 months duration
Metformin: Experimental	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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00780715

Locations

United Kingdom
Ninewells Hospital & Medical School
Dundee, United Kingdom, DD1 9SY

Sponsors and Collaborators

University of Dundee

Investigators

Principal Investigator:

Ewan R Pearson

University of Dundee

More Information

Responsible Party:	University of Dundee ( Ewan Pearson/Senior Lecturer )
Study ID Numbers:	2008DM05, EudraCT 2008-004790-18
Study First Received:	October 27, 2008
Last Updated:	December 24, 2008
ClinicalTrials.gov Identifier:	NCT00780715
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Dundee:

Diabetes therapies
Pharmacogenetics

Study placed in the following topic categories:

Metabolic Diseases
Gliclazide
Pioglitazone
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Sitagliptin

Additional relevant MeSH terms:

Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009