Kidney Transplant Recipient
Conditions
Brief summary
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).
Detailed description
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.
Interventions
Subcutaneous semaglutide 0.25mg for 4 weeks.
Subcutaneous semaglutide 0.5mg for 4 weeks.
Subcutaneous semaglutide 1.0 mg for 4 weeks.
Subcutaneous semaglutide 1.7 mg for 4 weeks
Subcutaneous semaglutide 2.4 mg for 8 weeks
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study will use a open-label single-arm clinical trial approach evaluating semaglutide in 37 KTR at risk for PTDM. Adult KTR between 4 and 12 weeks after transplant with an eGFR of at least 30 ml/min/1.73m2 at risk for PTDM will receive 24 weeks of semaglutide.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-hour OGTT | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 24 weeks | : 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. |
| Estimated GFR | 24 weeks | Calculated by CKD-EPI 2021 equation |
| Change in fasting blood glucose | 24 weeks | — |
| GFR | 24 weeks | Measured using 24-urine collection for creatinine, standardized per 1.73m2 body surface area. And estimated using CKD-EPI 2021 equation. |
| Change in serum insulin | 24 weeks | — |
| Change in HbA1c | 24 weeks | — |
| Albuminuria | 24 weeks | measuring urine albumin excretion from a 24-hour urine collection |
| Natriuresis | 24 weeks | Assessed with a 24-hour urine collection for sodium excretion |
| Percentage of body fat | 24 weeks | Bioimpedance analysis |
| Change in fasting lipid profile | 24 weeks | — |
| Change in liver enzymes | 24 weeks | ALT and AST |
| Change in fibrosis level | 24 weeks | Transient elastography |
| Change in steatosis level | 24 weeks | Transient elastography |
| Change in waist circumference | 24 weeks | — |
| Change in body weight | 24 weeks | — |
| Systolic blood pressure | 24 weeks | — |
| Diastolic blood pressure | 24 weeks | — |
| Mean arterial pressure | 24 weeks | — |
| Percentage of extracellular fluid | 24 weeks | Bioimpedance analysis |
Countries
Canada
Contacts
CONTACTCheng Xu
PRINCIPAL_INVESTIGATORSunita Singh, MD MSc FRCPC
University Health Network, Toronto General Hospital
Outcome results
None listed