Clinical trial NCT05240274: The POWERED Study: Prophylaxis With Metformin to Prevent PTDM
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post-transplant Diabetes Mellitus
New Onset Diabetes After Transplant
New Onset Diabetes After Transplantation
Kidney Transplant; Complications
Renal Transplantation
End Stage Renal Disease
Metformin
Keywords: post-transplant diabetes mellitus
new onset diabetes after transplant
renal transplant
kidney transplant
end-stage kidney disease
metformin
PTDM
NODAT
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
First posted: 2022-02-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single site, placebo controlled, double blind randomised clinical trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Diagnosis of post-transplant diabetes
timeFrame: 12 months post-renal transplant
Secondary outcomes:
measure: Pancreatic beta cell function
timeFrame: 12 months
measure: HbA1c
timeFrame: 12 months
measure: impaired glucose tolerance
timeFrame: 12 months
measure: patient and graft survival
timeFrame: 12 months
measure: incidence of treatment emergent adverse events
timeFrame: 12 months
measure: rejection
timeFrame: 12 months
measure: eGFR
timeFrame: 12 months
measure: diagnosis of PTDM in OGTT screen fails
timeFrame: 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal London Hospital, Barts Health NHS Trust
Study officials:
affiliation: Barts Health NHS Trust; Queen Mary University London
name: Kieran McCafferty, M.B., B.Chir
role: PRINCIPAL_INVESTIGATOR
References: