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

NCT00780715 | Completed Phase 4 Results

• 2 other identifiers: 2008DM05EudraCT 2008-004790-18
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes therapies; Pharmacogenetics

Outcome Measures

Primary Outcomes (1)

• HbA1c Change

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

  6 months

Study Arms (4)

Gliclazide MR

ACTIVE COMPARATOR

Drug: Gliclazide MR

Sitagliptin

ACTIVE COMPARATOR

Drug: Sitagliptin

Pioglitazone

ACTIVE COMPARATOR

Drug: Pioglitazone

Metformin

EXPERIMENTAL

Drug: Metformin

Interventions

Gliclazide MR DRUG

30mg daily increased to 60mg if HbA1c \> 7% at 3 months

Also known as: Diamicron MR

Gliclazide MR

Sitagliptin DRUG

Sitagliptin 100mg daily for 6 months

Sitagliptin

Pioglitazone DRUG

Pioglitazone 30mg daily , increased to 45mg daily if HbA1c \>7% at 3 months. 6 months duration

Also known as: Actos

Pioglitazone

Metformin DRUG

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

Metformin

Eligibility Criteria

• Age: 36 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (1)

Ninewells Hospital & Medical School

Dundee, DD1 9SY, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Gliclazide; Sitagliptin Phosphate; Pioglitazone; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Thiazolidinediones; Thiazoles; Biguanides; Guanidines; Amidines

Limitations and Caveats

Note that this study was a pilot study and was not designed or powered to show significance of differences in outcomes between groups. Primary aim was to demonstrate efficacy of novel route of recruitment from primary care.

Results Point of Contact

• Title: Professor Ewan Pearson
• Organization: University of Dundee

e.z.pearson@dundee.ac.uk

+44 (0) 1382 383387

Study Officials

• Ewan R Pearson

  University of Dundee

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Diabetic Medicine

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 28, 2008
• Study Start: December 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 26, 2017
• Results First Posted: October 26, 2017

Record last verified: 2017-10

Locations

GB (1)