search
Back to results

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

Primary Purpose

Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Gliclazide MR
Sitagliptin
Pioglitazone
Metformin
Sponsored by
University of Dundee
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Diabetes therapies, Pharmacogenetics

Eligibility Criteria

36 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ninewells Hospital & Medical School

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Experimental

Arm Label

Gliclazide MR

Sitagliptin

Pioglitazone

Metformin

Arm Description

Outcomes

Primary Outcome Measures

HbA1c Change
Units are absolute difference in %HbA1c (HbA1c being the percentage of glycated Haemoglobin, reflecting glucose exposure over the last 3 months)

Secondary Outcome Measures

Full Information

First Posted
October 27, 2008
Last Updated
October 25, 2017
Sponsor
University of Dundee
search

1. Study Identification

Unique Protocol Identification Number
NCT00780715
Brief Title
Response To Oral Agents in Diabetes (ROAD)- Pilot Study
Acronym
ROAD
Official Title
Response To Oral Agents in Diabetes (ROAD)- Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Dundee

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Diabetes therapies, Pharmacogenetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gliclazide MR
Arm Type
Active Comparator
Arm Title
Sitagliptin
Arm Type
Active Comparator
Arm Title
Pioglitazone
Arm Type
Active Comparator
Arm Title
Metformin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gliclazide MR
Other Intervention Name(s)
Diamicron MR
Intervention Description
30mg daily increased to 60mg if HbA1c > 7% at 3 months
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Intervention Description
Sitagliptin 100mg daily for 6 months
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
Pioglitazone 30mg daily , increased to 45mg daily if HbA1c >7% at 3 months. 6 months duration
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
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
Primary Outcome Measure Information:
Title
HbA1c Change
Description
Units are absolute difference in %HbA1c (HbA1c being the percentage of glycated Haemoglobin, reflecting glucose exposure over the last 3 months)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
36 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ewan R Pearson
Organizational Affiliation
University of Dundee
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ninewells Hospital & Medical School
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs