TriMaster: Study of a DPP4 Inhibitor, SGLT2 Inhibitor and Thiazolidinedione as Third Line Therapy in Patients With Type 2 Diabetes. (TriMaster)
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|ClinicalTrials.gov Identifier: NCT02653209|
Recruitment Status : Completed
First Posted : January 12, 2016
Last Update Posted : April 1, 2021
The aim of this project is to identify subgroups of patients with type 2 diabetes that respond well or poorly to particular drugs based on particular clinical characteristics such as their weight or kidney function, to enable better targeting of treatment for a particular individual.
This study will test 2 hypotheses of drug response supported by routine clinical and trial data. 600 patients with type 2 diabetes who have suboptimal glycaemic control on dual oral therapy will be recruited to a randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione. Each patient will take each study drug in addition to their existing treatment for four months at a time. At the end of each treatment the patient's glucose control will be measured and information about their experience of the drug will be collected.
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes||Drug: Sitagliptin - DPP4i Drug: Canagliflozin - SGLT2i Drug: Pioglitazone - TZD||Phase 4|
The study is a phase 4 randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as third line therapy in patients with Type 2 diabetes who have suboptimal glycaemic control on dual therapy with metformin and a sulphonylurea.
600 patients aged 30-80 who have been on stable doses of 2 classes of therapy (not including the trial IMPs or GLP1-agonist) for at least 3 months with HbA1c >58mmol/mol (7.5%) will receive three double-blinded third-line non-injectable therapies. On recruitment into the study participants will have underlying pathophysiology assessed in a mixed-meal tolerance test (MMTT) and samples will be collected for baseline analysis and storage for future biomarker analysis and discovery. Participants will then receive 16 weeks of each over-encapsulated blinded therapy in random order.
At the end of each treatment period, fasting blood will be taken to measure glycaemic response (HbA1c), fasting glucose and insulin concentrations trough drug levels and to confirm continued eligibility. Weight, blood pressure and. data about patient experience will also be collected including perceived side effects, preparedness to remain on therapy, psychological health and health related quality of life.
At the end of the study, patient treatment preference will be recorded after feeding back to the patient for each of the 3 therapies their HbA1c, weight change, frequency of hypoglycaemias, any patient reported side effects and the patient's verdict on each therapy will be recorded. Each participant will be asked which treatments they would take long term and the reason for their preference.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||525 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||TriMaster: Randomised Double-Blind Crossover Study of a DPP4 Inhibitor, SGLT2 Inhibitor and Thiazolidinedione as Third Line Therapy in Patients With Type 2 Diabetes Who Have Suboptimal Glycaemic Control on Dual Therapy With Metformin and a Sulphonylurea|
|Actual Study Start Date :||November 1, 2016|
|Actual Primary Completion Date :||January 2021|
|Actual Study Completion Date :||January 2021|
|Experimental: Sitagliptin - DPP4i||
Drug: Sitagliptin - DPP4i
DPP4 inhibitor 100mg supplied as over-encapsulated hard capsule shell to be taken orally, once a day for 16 weeks in addition to existing prescribed oral diabetes therapy.
Other Name: Januvia
|Experimental: Canagliflozin - SGLT2i||
Drug: Canagliflozin - SGLT2i
SGLT2 inhibitor 100mg supplied as over-encapsulated hard capsule shell to be taken orally, once a day for 16 weeks in addition to existing prescribed oral diabetes therapy.
Other Name: Invokana
|Experimental: Pioglitazone - TZD||
Drug: Pioglitazone - TZD
Thiazolidinedione 30mg supplied as over-encapsulated hard capsule shell to be taken orally, once a day for 16 weeks in addition to existing prescribed oral diabetes therapy.
Other Name: Actos
- On treatment HbA1c in obese patients (BMI >30kgm-2), compared to non-obese patients [ Time Frame: 16 weeks ]
Outcome measure will test hypothesis that patients with insulin resistance, characterised clinically by a raised BMI (>30 kg/m2), compared to non-obese patients, will:
- Respond well to pioglitazone, a thiazolidinedione that works as an insulin sensitiser.
- Respond less well to sitagliptin, a DPP4i, which works through stimulating endogenous insulin secretion post-prandially.
- On treatment HbA1c in patients with an eGFR <90 mls/min/1.73m2 compared to patients with an eGFR >90 mls/min/1.73m2. [ Time Frame: 16 weeks ]
Outcome measure will test hypothesis that patients with modestly reduced estimated glomerular filtration rate (eGFR 60-90 mls/min/1.73m2), compared to those with eGFR >90 mls/min/1.73m2, will:
- Respond poorly to canagliflozin, a SGLT2 inhibitor, which works through inhibiting the active reabsorption of glucose in the proximal tubule, as the reduced eGFR will reduce the glucose-lowering efficacy.
- Respond well to sitagliptin, a DPP4i that is renally cleared, as the reduced eGFR will increase plasma DPP4i concentrations.
- Patient preference [ Time Frame: 48-54 weeks (3 x 16 weeks of therapy) ]Patient treatment preference of study drug within hypothesised strata and overall
- Prevalence of side effects [ Time Frame: 48-54 weeks (3 x 16 weeks of therapy) ]Prevalence of side effects within hypothesised strata and for specific drugs, to include: weight gain, hypoglycaemia, oedema, genital tract infection and discontinuation of therapy
- HbA1c on therapy against predefined test of gender heterogeneity [ Time Frame: 16 weeks ]Predefined test of gender heterogeneity with pilot data suggesting females are likely to show an improved response relative to males for pioglitazone.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02653209
|Exeter Clinical Research Facility|
|Exeter, United Kingdom, EX2 5DW|
|Principal Investigator:||Andrew Hattersley||University of Exeter / Royal Devon & Exeter NHS Trust|