The POWERED Study: Prophylaxis With Metformin to Prevent PTDM

Barts & The London NHS Trust

Status and phase: Completed; Phase 2

Conditions: Metformin; New Onset Diabetes After Transplantation; Kidney Transplant; Complications; End Stage Renal Disease; Renal Transplantation; New Onset Diabetes After Transplant; Post-transplant Diabetes Mellitus

Treatments: Drug: Metformin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05240274

203080

Details and patient eligibility

About

PrOphylaxis With mEtformin to pREvent PTDM: a single site, placebo controlled, double blind randomised clinical trial evaluating the effectiveness of metformin to prevent post-transplant diabetes in a cohort of patients undergoing renal transplantation.

Full description

Renal transplantation is the optimal form of renal-replacement therapy in end-stage kidney disease. However, up to 30% of new renal transplants develop post-transplant diabetes mellitus (PTDM). The development of PTDM is associated with adverse graft and patient survival outcomes and represents an increased financial burden. There is an urgent clinical need to discover therapies which could decrease the risk of developing PTDM. Metformin offers a safe and cheap therapeutic option which has been demonstrated to reduce the incidence of type 2 diabetes in a high-risk non-transplant patient group. The investigators propose to study its safety and efficacy in preventing the development of PTDM.

POWERED is a single site, placebo-controlled, double- blind randomised clinical trial of metformin in patients without pre-existing diabetes mellitus who have received a new renal transplant. Eligible, consented patients are randomised to a 3 month course of either active drug or placebo within 10 days post-transplant. All patients will receive the usual standard of care for transplant patients. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. The primary endpoint is the development of PTDM as defined by a positive oral glucose tolerance test (OGTT). Secondary endpoints include graft outcomes, pancreatic b-cell function and safety endpoints. The study began recruitment in January 2019 and plans to enrol 60 patients. There are no interim analyses planned.

Ethical approval was obtained from the London - Brighton and Sussex Ethics Committee (REC 18/LO/0958) prior to commencing the study. All study-related data will be used by the Sponsor in accordance with local data protection law. Results of the trial will be submitted for publication in a peer-reviewed journal.

Enrollment: 60 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients (male or female) undergoing renal transplantation under the care of the Barts Health NHS Trust Renal Department
2. Aged 18-75 inclusively
3. Willing to comply with study schedule

Exclusion criteria

1. History of Type 1 or type 2 diabetes
2. Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease
3. Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug
4. Subject with a known hypersensitivity or contraindication to Tacrolimus
5. Subject with a known hypersensitivity or contraindication to Metformin
6. Pregnant or breast feeding

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Metformin

Active Comparator group

Description:

metformin 500mg OD

Treatment:

Drug: Metformin

Placebo

Placebo Comparator group

Description:

placebo 500mg OD

Treatment:

Drug: Placebo