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

October 25, 2017 updated by: Ewan Pearson, University of Dundee

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.

Study Overview

Status

Completed

Conditions

Intervention / 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. The primary outcome of the pilot is HbA1c change. Other measures regarding recruitment and dose titration will be assessed. 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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

36 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Gliclazide MR
Drug: Gliclazide MR
30mg daily increased to 60mg if HbA1c > 7% at 3 months
Other Names:
  • Diamicron 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HbA1c Change
Time Frame: 6 months
Units are absolute difference in %HbA1c (HbA1c being the percentage of glycated Haemoglobin, reflecting glucose exposure over the last 3 months)
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Dundee

Investigators

  • Principal Investigator: Ewan R Pearson, University of Dundee

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (ACTUAL)

October 1, 2009

Study Completion (ACTUAL)

October 1, 2009

Study Registration Dates

First Submitted

October 27, 2008

First Submitted That Met QC Criteria

October 27, 2008

First Posted (ESTIMATE)

October 28, 2008

Study Record Updates

Last Update Posted (ACTUAL)

October 26, 2017

Last Update Submitted That Met QC Criteria

October 25, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008DM05
  • EudraCT 2008-004790-18

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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