Glucagon-like-peptide-1 Receptor Agonists in Patients Receiving Maintenance Dialysis (GUARD-1)

Unity Health Toronto

Status and phase

Begins enrollment this month

Phase 4

Conditions

Diabetes

Dialysis

End Stage Kidney Disease (ESRD)

Kidney Disease, Chronic

Treatments

Drug: Semaglutide Pen

Study type

Interventional

Funder types

Other

Identifiers

NCT07017270

CTO5185

Details and patient eligibility

About

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.

Full description

In this randomized pilot study, Individuals randomized to the active intervention arm will take semaglutide once weekly. Semaglutide (injectable, 1.34 mg/mL) is delivered subcutaneously via a multiple-use pen-injector that can be used to dial in all required doses on the same pen-injector. The clinical pen has a drum scale of 1-80 in increments of 1. Participants will be trained/re-trained on injector use at 0, 4, 8, and 12 weeks. For participants receiving in-centre hemodialysis, the intervention may be administered during the dialysis session by nursing personnel. Semaglutide will be titrated using an algorithm used in previous trials with a starting dose of 0.25 mg/week, with an increase to 0.5 mg/week after 4 weeks, and to the maximum dose of 1.0 mg/week after 8 weeks as tolerated. If a participant experiences an adverse effect, efforts will be made to maintain the current dosage, with dose reductions or treatment pauses permitted at the discretion of the site investigator. Patient receiving concomitant insulin therapy will have therapy adjusted as per a pre-specified algorithm. Participants allocated to the usual care arm will receive usual care.

Primary outcomes:

Feasibility of study recruitment: ≥ 40% of fully eligible patients consent to participate in the trial.
Adherence to intervention: ≥ 70% of enrolled patients are adherent to the study intervention over the 26-week follow-up period.
Ability to follow: ≥ 90% of participants will be successfully followed to week

Secondary outcomes:

Proportion Discontinuing Intervention
Safety Events
Major Adverse Cardiovascular Outcomes (Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event)
Body Weight/BMI
Systolic/diastolic blood pressure
Insulin dosage, glycemic control (HbA1c and random glucose)
Lipid profile
Hemoglobin, Calcium, Phosphate, PTH
EQ-5D-5L for baseline-adjusted changes in quality of life and symptom burden

Enrollment

100 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥ 18
Receiving chronic maintenance hemodialysis or peritoneal dialysis for ≥ 90 days
confirmed DM2 based on medical history and current or prior receipt of an oral hypoglycemic agent and/or insulin.
Ability to provided informed consent or through their substitute decision maker

Exclusion criteria

Type 1 DM
Use of a GLP-1-RA within 30 days prior to screening
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)
Confirmed pregnancy, women of childbearing potential
Known hypersensitivity to GLP-1-RA
Expected to recover kidney function, stop hemodialysis, pursue palliative care, or transplantation within 6 months
Enrolment in another clinical trial judged by the investigator to interact with the effect of GLP1-RA