Chronic Kidney Disease, Obesity
Conditions
Keywords
Weight Management, Transplant, GLP-1RA, Pilot Study, Registries, Pragmatic
Brief summary
OK-TRANSPLANT 2 is a vanguard study for a large randomized, pragmatic, open-label trial. We will randomize participants with obesity, high-risk CKD/dialysis who are hoping for lose weight for the purpose of kidney transplant. Subjects will either be enrolled on a virtual weight management program or continue their usual care.
Detailed description
Obesity is well-recognized as an independent risk factor for chronic kidney disease (CKD) including end-staged kidney disease (ESKD). In people with ESKD, obesity can preclude access to lifesaving kidney transplantation. Of solid organ transplant programs in Canada, 80% exclude people with obesity (based upon body mass index or BMI), due to a potential risk of perioperative complications and post-transplant mortality. Losing weight for kidney transplantation can, however, be extremely difficult. Medications that can promote weight loss in other populations including glucagon-like peptide 1 receptor agonists (GLP-1RA; liraglutide, semaglutide, and dulaglutide) and glucose-dependent insulinotropic polypeptide (GIP-1RA)/GLP-1RAs (tirzepatide), have not been studied in devoted trials of advanced CKD participants, and their efficacy and safety remain unclear. Nutritional advice is often very difficult to follow when trying to balance kidney and diabetes diets (e.g. potassium), and if diets are too restrictive, there may be protein-energy wasting which could be detrimental to patients. People with high-risk CKD frequently live with functional impairment which can limit exercise. Weight loss programs can be cost prohibitive to those who are already socioeconomically disadvantaged. A vanguard is needed before a large, multicentered RCT: A feasibility study will allow us to ensure that we can recruit a sufficient sample of participants into our trial, that our trial processes are inclusive, and that they are acceptable to patients. In the vanguard phase of our trial, we will answer the following questions: 1. Is participant recruitment into a large multi-centered trial feasible? 2. Will participants remain adherent to their assigned treatment arm over 26 weeks of study? 3. Will participants find our program acceptable? 4. Will safety events preclude us from testing our intervention in a larger RCT?
Interventions
DRUGSemaglutide
Maximum tolerated dose of semaglutide subcutaneously once weekly. Maximum dose of 2.0 mg.
BEHAVIORALVirtual Weight Management Coaching
Virtual meeting with intervention coach once every 4 weeks for 6 months, where the coach will discuss the goals and progress with participant, nutritional advice, exercise advice, and motivational support.
Sponsors
Western University, Canada
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Queen Elizabeth II Health Sciences Centre
Unity Health Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Double: Double (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 18 years or older * BMI; 35 kg/m\^2 * 10% risk of ESKD requiring renal replacement therapy over 2 years or receiving dialysis
Exclusion criteria
* Known contraindication to a GLP-1RA (pancreatitis, personal or family history of medullary thyroid cancer, hypersensitivity) * Type 1 diabetes * No access to semaglutide via drug coverage * Pregnant, breastfeeding or planning to become pregnant * Currently in a GLP-1RA or GLP-1RA/GIP study or planning to be in one
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Recruitment | 12 months | Number of participants enrolled across three centers, with success defined as recruitment of ≥ 60 participants within the 12-month enrollment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adherence to Scheduled Coaching Visits | 12 months | Percentage of participants randomized to the intervention attend \>75% of their scheduled coaching visits. |
| Adherence to GLP-1RA Therapy | 12 months | Percentage of participants randomized to the intervention fill \>75% of their semaglutide prescriptions. |
| Recruitment of ≥20 Participants in First 12 Weeks | First 12 weeks | Recruitment of ≥20 participants in first 12 Weeks of trial initiation |
| Recruitment Per Site Within 12 Weeks | First 12 weeks | At least one participant recruited per site within 12 weeks of trial initiation each active site |
| Incidence of Acute Kidney Injury | 12 months | Number of participants experiencing acute kidney injury (AKI) |
| Incidence of Hypoglycemia | 12 months | Number of participants experiencing hypoglycemia |
| Incidence of Gastrointestinal Side Effects | 12 months | Number of participants experiencing GI side effects |
| Change in Dalhousie Clinical Frailty Scale Classification | 26 weeks | Change in participant's Dalhousie Clinical Frailty Scale Classification from baseline to 26 weeks. The scale has 9 options, from 1 (very fit) to 9 (terminally ill). |
| Change in SARC-F Score of Sarcopenia | 26 weeks | Change in participant's SARC-F questionnaire score from baseline to 26 weeks. Out of 8 points, a SARC-F score of ≥4 best predicts the need for further, more comprehensive clinical evaluation. |
| Change in Body Weight - Smart Scale | 26 weeks | Change in weight from baseline to 26 weeks, measured in kilograms. Measured using a Smart Scale in a subpopulation. |
| Change in Body Fat - Smart Scale | 26 weeks | Change in body fat from baseline to 26 weeks, measured in percentage. Measured using Smart Scale in subpopulation. |
| Change in Muscle Mass - Smart Scale | 26 weeks | Change in muscle mass from baseline to 26 weeks. Measured in kilograms. Measured using Smart Scale in subpopulation. |
| Change in Body Water Content - Smart Scale | 26 weeks | Change in body water content from baseline to 26 weeks. Measured in percentage. Measured using Smart Scale in subpopulation. |
| In-Clinic Height Measurement | Baseline, 3 months, 6 months | In-clinic height measurements, measured in centimeters |
| In-Clinic Weight Measurement | Baseline, 3 months, 6 months | In-clinic weight measurements, measured in kilograms |
| In-Clinic Body Mass Index Measurement | Baseline, 3 months, 6 months | In-clinic BMI measurements, measured in kg/m\^2 |
Countries
Canada
Contacts
CONTACTHeather LaPier, BSc
PRINCIPAL_INVESTIGATORKristin K Clemens, MD, MSc
St. Joseph's Health Care London
PRINCIPAL_INVESTIGATORLouise Moist, MD, MSc
London Health Sciences Centre
Outcome results
None listed