Semaglutide for the Prevention Of Post-Transplant Diabetes Mellitus

Phase 3Not Yet RecruitingNCT06913023

University Health Network, Toronto37 enrolled

Overview

The study aims to determine the short-term efficacy, mechanisms and safety of 24 weeks of semaglutide therapy in 37 KTR at risk of post-transplant diabetes mellitus (PTDM).

A kidney transplant is the best treatment for people living with kidney failure as it allows people to live longer with a better quality of life. However, one in four kidney transplant recipients will develop diabetes after transplant. This is largely due to the medications that must be used to prevent rejection of the transplant. Kidney transplant recipients who get diabetes after transplant are up to three times more likely to have heart disease and die prematurely. To date, there are no treatments to prevent the development of diabetes after kidney transplant. Semaglutide is a drug that is commonly used to treat diabetes and obesity. The investigators believe that semaglutide is a safe and effective drug which can prevent the development of diabetes in kidney transplant recipients. Therefore, the investigators are conducting a study where kidney transplant recipients who are at increased risk of developing diabetes after transplant will receive semaglutide for 24 weeks after their transplant. The study will determine whether semaglutide is effective in decreasing blood sugar levels and the rate of diabetes. The investigators will also study other important markers of health including body weight and cholesterol levels as well as liver, kidney and heart function. Diabetes after transplant is a common problem, and preventing it is extremely important to allowing kidney transplant recipients to live longer and better lives. The results of this study will allow the investigators to determine if semaglutide is a safe and effective option for the prevention of diabetes in kidney transplant recipients.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Kidney Transplant Recipient

Interventions

Semaglutide 0.25 mgDRUG

Subcutaneous semaglutide 0.25mg for 4 weeks.

Semaglutide 0.5 mgDRUG

Subcutaneous semaglutide 0.5mg for 4 weeks.

Semaglutide 1.0 mgDRUG

Subcutaneous semaglutide 1.0 mg for 4 weeks.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed and dated written informed consent. 2. Adult (≥18 years) recipients of a living or deceased donor kidney transplant 3. Between 4- and 12-weeks post kidney transplant 4. Stable kidney function defined as an eGFR \> 30 ml/min/1.73m2 (CKD-EPI) 5. At risk for PTDM at the time of transplant based on the following criteria: 1. BMI ≥ 25 kg/m2, or 2. Fasting plasma glucose 6.1-6.9 mmol/L (impaired fasting glucose), or 3. 2hr OGTT plasma glucose 7.8-11.0 (impaired glucose tolerance), or 4. HbA1C 5.5-6.4% (at risk for DM or prediabetes). Exclusion Criteria: 1. Established diagnosis of type 1 or type 2 DM as per Diabetes Canada (including the need for glucose-lowering therapy for hyperglycemia at the time of screening) 2. Kidney-Pancreas transplant recipient 3. Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening 4. History of pancreatitis 5. Personal or family history of medullary thyroid cancer or MEN2B 6. Women who are pregnant, nursing or plan on becoming pregnant whilst in the trial 7. Use of GLP1RA in the 30 days prior to screening 8. Contraindication to MRI (applicable only to those undergoing the optional MRI assessments) 9. With known or suspected hypersensitivity to semaglutide or related products 10. Patient not able to understand and comply with study requirements, based on Investigator's judgment. 11. Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcom 12. History of glucose-galactose malabsorption syndrome

Locations (2)

St. Paul's Hospital

Vancouver, British Columbia, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

2-hour OGTT

The primary outcome of this study is the change in plasma glucose at 120 minutes following a 75g oral glucose challenge (2-hour OGTT) at 24 weeks. The 2-hour OGTT was selected as the primarily outcome in this study for the following reasons: 1) In selecting a surrogate outcome for PTDM in KTR, there are limitations to HbA1c and fasting glucose in this population; 2) The 2-hour OGTT is the recommended test for the diagnosis of PTDM in KTR and 3) The use of OGTT has been used in other PTDM prevention studies.

Time frame: 24 weeks

Secondary Outcomes

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

: The side effects of GLP-1RA have been well described and will be assessed at each study visit. Adverse events include AKI, hypoglycemia, volume depletion, GI intolerance, amputations, pancreatitis, hepatobiliary complications and injection site or allergic reactions, infectious complications (any source), and malignancy. Episodes of biopsy-proven acute rejection (as defined by the Banff criteria), death-censored graft failure (defined as the need for initiation of chronic dialysis or re-transplantation) or death with graft function (defined as death with a functioning allograft) will also be collected. Kidney transplantation assures complete denervation of the transplanted kidney and the renal vasoconstrictive response in the setting of intravascular volume depletion is diminished in KTR. Therefore, frequent monitoring for adverse events has been integrated in our study design, occurring on 10 separate occasions, to capture these adverse events should they occur.

Time frame: 24 weeks

Estimated GFR

Calculated by CKD-EPI 2021 equation

Time frame: 24 weeks

Change in fasting blood glucose

Time frame: 24 weeks

GFR

Measured using 24-urine collection for creatinine, standardized per 1.73m2 body surface area. And estimated using CKD-EPI 2021 equation.

Central Contacts

Cheng Xu

CONTACT

416-340-4800 cheng.xu@uhn.ca

Data from ClinicalTrials.gov

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