Response To Oral Agents in Diabetes (ROAD)- Pilot Study
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Gliclazide MR; Sitagliptin; Pioglitazone; Metformin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 30mg daily increased to 60mg if HbA1c > 7% at 3 months; Sitagliptin 100mg daily for 6 months; Pioglitazone 30mg daily , increased to 45mg daily if HbA1c >7% at 3 months. 6 months duration; 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
Other intervention name(s): Diamicron MR; Actos
Intervention MeSH terms: Metformin; Pioglitazone; Sitagliptin Phosphate; Gliclazide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes therapies; Pharmacogenetics