Diabetes, Dialysis, End Stage Kidney Disease (ESRD), Kidney Disease, Chronic
Conditions
Keywords
Dialysis, Type 2 diabetes, semaglutide, end stage kidney disease, GLP1, GLP1RA
Brief summary
This study aims to determine if GLP1RA is safe and tolerable in maintenance dialysis population, adherence, and feasibility of a larger definitive cardiovascular outcome trial in this population. Participants will be randomized 1:1 to either weekly subcutaneous semaglutide versus usual care and followed for 26 weeks.
Detailed description
The proposed study is a parallel group, pilot randomized controlled trial. The trial will recruit 100 participants across Canadian hospitals and potentially others worldwide. We will recruit patients receiving maintenance dialysis for ≥ 90 days who have a background of type 2 diabetes mellitus. We will exclude patients with type 1 diabetes mellitus and recent recipients of a GLP-1-RA. Participants will be randomized 1:1 to either weekly subcutaneous semaglutide versus usual care and followed for 26 weeks. The key feasibility outcomes are: (1) successful recruitment of fully eligible patients (≥40%); (2) adherence to the study intervention (≥70% participants take at least 70% of prescribed study drug doses); and (3) completeness of follow-up (≥90% participants are successfully followed to 26 weeks). Secondary outcomes will include adverse events, major adverse cardiovascular events, changes in body weight, glycemic control, insulin dosage, blood pressure, lipid parameters, markers of CKD-related bone mineral disease, and quality of life. As a pilot RCT, GUARD-1 will focus on the safety and tolerability of the GLP-1-RA semaglutide in the maintenance dialysis population. The key question of this trial is whether an RCT to evaluate the cardiovascular effects of GLP-1-RA in the maintenance dialysis population is feasible based on study recruitment, adherence, follow-up and safety.
Interventions
DRUGSemaglutide Pen
Individuals randomized to this arm will take semaglutide once weekly. For participants receiving in-centre hemodialysis, the intervention may be administered during the dialysis session by nursing personnel based on the patient's preference.
Sponsors
Unity Health Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 2. Receiving chronic maintenance hemodialysis or peritoneal dialysis for ≥ 90 days 3. confirmed DM2 based on medical history and current or prior receipt of an oral hypoglycemic agent and/or insulin. 4. Ability to provided informed consent or through their substitute decision maker
Exclusion criteria
1. Type 1 DM 2. Use of a GLP-1-RA within 30 days prior to screening 3. Personal or first-degree relative(s) with a history of type 2 multiple endocrine neoplasia syndrome or medullary thyroid cancer, or acute pancreatitis (within 180 days of study screening) 4. Confirmed pregnancy, women of childbearing potential 5. Known hypersensitivity to GLP-1-RA 6. Expected to recover kidney function, stop hemodialysis, pursue palliative care, or transplantation within 6 months 7. Enrolment in another clinical trial judged by the investigator to interact with the effect of GLP1-RA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence of Study Intervention | 26 weeks | This will be determined if ≥ 70% of enrolled number of eligible participants (who are randomized) are adherent to the study intervention over the 26-week follow-up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Medication Discontinuation | 26 weeks | The number of enrolled participants who permanently discontinue the study medication in the semaglutide arm from baseline to 6 months. |
| Feasibility of Study Recruitment | 26 weeks | This will be determined if ≥ 40% of the number of fully eligible participants (potential participants who were screened and identified to meet inclusion/exclusion criteria) consent to participate in the trial. |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 26 weeks | We will measure the incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\] and identify safety events of special interest such as gastrointestinal symptoms, acute biliary disease, acute pancreatitis, interventions for diabetic retinopathy, heart failure exacerbations, malignant neoplasms, and the number of hypoglycemic events. |
| Major Adverse Cardiovascular Events | 26 weeks | This is a composite of CV death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event. |
| Follow Up Percentage at 26 weeks | 26 weeks | To determine if ≥ 90% of participants (who are enrolled) will be successfully followed to week 26 (end of study participation). |
| Patient Reported Measures | 26 weeks | The validated EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) score will be used to evaluate baseline-adjusted changes in quality of life and symptom burden. The EQ-5D-5L asks individuals to rate their overall health on a visual scale from 0 to 100, where 0 represents the worst imaginable health and 100 represents the best imaginable health. |
Countries
Canada
Contacts
CONTACTRon Wald, MD
CONTACTKevin Yau, MD
PRINCIPAL_INVESTIGATORDr. Ron Wald, MD
Unity Health Toronto
Outcome results
None listed