The POWERED Study: Prophylaxis With Metformin to Prevent PTDM

End Stage Renal Disease Clinical Trial

— POWERED  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05240274
• Other study ID #: 203080
• Status: Completed
• Phase: Phase 2
• Start date: January 25, 2019
• Est. completion date: August 30, 2022

Study information

• Verified date: November 2021
• Source: Barts & The London NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 30, 2022
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• End Stage Renal Disease
• Kidney Failure, Chronic
• Kidney Transplant; Complications
• Metformin
• New Onset Diabetes After Transplant
• Post-transplant Diabetes Mellitus
• Renal Transplantation

Intervention

Drug:
• Metformin
metformin 500mg OD for 3 months to start within 10 days post-renal transplant
• Placebo
placebo 500mg OD for 3 months to start within 10 days post-renal transplant

Locations

Country	Name	City	State
United Kingdom	Royal London Hospital, Barts Health NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Barts & The London NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnosis of post-transplant diabetes	Positive 2 hour oral glucose tolerance test (i.e. 2 hour sugar >11.1 mol/L)	12 months post-renal transplant
Secondary	Pancreatic beta cell function	change in calculated HOMA-IR using C-peptide measurement between baseline and month 3 using	12 months
Secondary	HbA1c	HbA1c	12 months
Secondary	impaired glucose tolerance	impaired glucose tolerance as per 2 hour oral glucose tolerance test (i.e. 2 hour glucose 7.9-11.1 mmol/L)	12 months
Secondary	patient and graft survival	patient survival, kidney transplant (graft) survival	12 months
Secondary	incidence of treatment emergent adverse events	patient safety: adverse events, serious adverse events	12 months
Secondary	rejection	episodes of acute transplant rejection	12 months
Secondary	eGFR	renal transplant function	12 months
Secondary	diagnosis of PTDM in OGTT screen fails	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	12 months