The POWERED Study: Prophylaxis With Metformin to Prevent PTDM

Sponsor

Barts & The London NHS Trust (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05240274

Collaborator

(none)

Enrollment

Location

Arms

42.2

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post-transplant Diabetes Mellitus New Onset Diabetes After Transplant New Onset Diabetes After Transplantation Kidney Transplant; Complications Renal Transplantation End Stage Renal Disease Metformin	Drug: Metformin Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single site, placebo controlled, double blind randomised clinical trialSingle site, placebo controlled, double blind randomised clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Both the patient and the study team will be blinded to the treatment intervention. The clinical team will also be blinded. Pharmacy staff who dispense the IMP will not be blinded, nor will Sponsor Office staff responsible for reporting unblinded SUSAR reports to the MHRA.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jan 25, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metformin metformin 500mg OD	Drug: Metformin metformin 500mg OD for 3 months to start within 10 days post-renal transplant
Placebo Comparator: Placebo placebo 500mg OD	Drug: Placebo placebo 500mg OD for 3 months to start within 10 days post-renal transplant

Arm

Intervention/Treatment

Active Comparator: Metformin

metformin 500mg OD

Drug: Metformin

metformin 500mg OD for 3 months to start within 10 days post-renal transplant

Placebo Comparator: Placebo

placebo 500mg OD

Drug: Placebo

placebo 500mg OD for 3 months to start within 10 days post-renal transplant

Outcome Measures

Primary Outcome Measures

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

Pancreatic beta cell function [12 months]
change in calculated HOMA-IR using C-peptide measurement between baseline and month 3 using
HbA1c [12 months]
HbA1c
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
incidence of treatment emergent adverse events [12 months]
patient safety: adverse events, serious adverse events
rejection [12 months]
episodes of acute transplant rejection
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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