TriMaster: Study of a DPP4 Inhibitor, SGLT2 Inhibitor and Thiazolidinedione as Third Line Therapy in Patients With Type 2 Diabetes.
NCT ID: NCT02653209
Last Updated: 2021-04-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
525 participants
INTERVENTIONAL
2016-11-01
2021-01-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Treatment Preference for Weekly Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Versus Daily DPP-4 Inhibitors in Participants With Type 2 Diabetes Mellitus
NCT03231709
To Assess Safety, Tolerability, Pharmacokinetics/Pharmacodynamics and the Effect of Fasting After Single Oral Doses of AZD5658 in Type 2 Diabetes
NCT01176097
An Exploratory Study of the Effects of Trelagliptin and Alogliptin on Glucose Variability in Patients With Type 2 Diabetes Mellitus
NCT02771093
iSGLT2 Inhibitor and a iDPP -4 Inhibitor in Treatment of Type 2 Diabetes Mellitus in Patients Treated With Metformin (TRIAD)
NCT06560333
Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes
NCT02946632
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
CROSSOVER
TREATMENT
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Sitagliptin - DPP4i
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.
Canagliflozin - SGLT2i
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.
Pioglitazone - TZD
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
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.
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 Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Age ≥30 and ≤80
* Currently treated with two classes of oral glucose-lowering therapy (given either as separate or combined medications), that do not include a DPP4-inhibitor, a SGLT2-inhibitor or a thiazolidinedione.
* Diabetes duration ≥12months
* No change in diabetes treatment (new treatments or dose change) within previous 3 months
* HbA1c \> 58mmol/mol (7.5%) and ≤110mmol/mol (12.2%) - confirmed at screening visit
* eGFR ≥ 60mls/min/1.73m² - confirmed at screening visit
* Able and willing to give informed consent
Exclusion Criteria
* HbA1c ≤ 58mmol/mol (7.5%) or \>110mmol/mol (12.2%)
* eGFR \<60mls/min/1.73m².
* Diabetes duration \<12 months
* ALT \>2.5 x upper limit of the assay normal range or known liver disease, specifically \>30 μmol/L that is associated with other evidence of liver failure.
* Insulin treated within the last 12 months
* Limb ischaemia shown by absence of both pulses in one or both feet.
* Currently treated with corticosteroids
* Currently treated with rifampicin, gemfibrozil, phenytoin and carbamazepine
* Active infection (any infection requiring antibiotics at present)
* Foot ulcer requiring antibiotics within previous three months
* Recent (within 3 months) significant surgery or planned surgery (excluding minor procedures)
* Acute cardiovascular episode (angina, myocardial infarction, stroke, transient ischemic episode) occurring within the previous 3 months
* History of heart failure
* Current use of loop diuretic therapy (Furosemide or Bumetanide)
* History of bladder carcinoma
* Current/ongoing investigation for macroscopic haematuria
* History of Diabetic Ketoacidosis
* History of pancreatitis
* Pregnant, breastfeeding or planning a pregnancy over the study period
* Concurrent Participation on another Clinical Trial of an Investigational Medicinal Product, where the IMP is currently being taken, or without sufficient washout period\* and without consultation with the CTIMP research team.
* Unable or unwilling to give informed consent
* Sufficient washout period = five times the half-life of the IMP / potential IMP if involving a placebo / longest half-life if a trial includes more than one drug
30 Years
80 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Exeter
OTHER
NHS Tayside
OTHER_GOV
University of Dundee
OTHER
University of Glasgow
OTHER
Newcastle University
OTHER
King's College London
OTHER
Royal Devon and Exeter NHS Foundation Trust
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Andrew Hattersley
Role: PRINCIPAL_INVESTIGATOR
University of Exeter / Royal Devon & Exeter NHS Trust
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Exeter Clinical Research Facility
Exeter, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Shields BM, Angwin CD, Shepherd MH, Britten N, Jones AG, Sattar N, Holman R, Pearson ER, Hattersley AT. Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study. Nat Med. 2023 Feb;29(2):384-391. doi: 10.1038/s41591-022-02121-6. Epub 2022 Dec 7.
Shields BM, Dennis JM, Angwin CD, Warren F, Henley WE, Farmer AJ, Sattar N, Holman RR, Jones AG, Pearson ER, Hattersley AT; TriMaster Study group. Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study. Nat Med. 2023 Feb;29(2):376-383. doi: 10.1038/s41591-022-02120-7. Epub 2022 Dec 7.
Angwin C, Jenkinson C, Jones A, Jennison C, Henley W, Farmer A, Sattar N, Holman RR, Pearson E, Shields B, Hattersley A; MASTERMIND consortium. TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea-a MASTERMIND study protocol. BMJ Open. 2020 Dec 21;10(12):e042784. doi: 10.1136/bmjopen-2020-042784.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2015-002790-38
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
12039221
Identifier Type: REGISTRY
Identifier Source: secondary_id
MR/N00633X/1
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
1603221
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.