The POWERED Study: Prophylaxis With Metformin to Prevent PTDM

Phase 2

Completed

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

• Registration Number: NCT05240274
• Lead Sponsor: Barts & The London NHS Trust

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2019-01-25
• Status Verified: 2021-11
• Study First Submitted: 2022-01-17
• Study First Submitted QC: 2022-02-04
• Study First Posted: 2022-02-15
• Primary Completion: 2022-05-30
• Study Completion: 2022-08-30
• Last Update Submitted: 2022-10-17
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	metformin 500mg OD
Placebo	Placebo	placebo 500mg OD

Primary Outcome Measures

Name	Time	Method
Diagnosis of post-transplant diabetes	12 months post-renal transplant	Positive 2 hour oral glucose tolerance test (i.e. 2 hour sugar \>11.1 mol/L)

Secondary Outcome Measures

Name	Time	Method
Pancreatic beta cell function	12 months	change in calculated HOMA-IR using C-peptide measurement between baseline and month 3 using
incidence of treatment emergent adverse events	12 months	patient safety: adverse events, serious adverse events
impaired glucose tolerance	12 months	impaired glucose tolerance as per 2 hour oral glucose tolerance test (i.e. 2 hour glucose 7.9-11.1 mmol/L)
patient and graft survival	12 months	patient survival, kidney transplant (graft) survival
eGFR	12 months	renal transplant function
diagnosis of PTDM in OGTT screen fails	12 months	incidence of PTDM in patients not randomised to study due to positive OGTT at screening: defined by appearance of PTDM on problem list or prescription of an anti-diabetic drug
HbA1c	12 months	HbA1c
rejection	12 months	episodes of acute transplant rejection

Trial Locations

Locations (1)

Royal London Hospital, Barts Health NHS Trust; 🇬🇧 London, United Kingdom