The Efficacy, Mechanism & Safety of Sodium Glucose Co-Transporter-2 Inhibitor & Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Kidney Transplant Recipients

NCT ID: NCT05938712

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-24
• Study Completion Date: 2025-10-01

Brief Summary

The study aims to determine the short-term efficacy, mechanisms and safety of 12 weeks of dapagliflozin and semaglutide combination therapy in 20 KTR, with and without T2D.

Detailed Description

Kidney transplantation improves survival and quality of life for patients with kidney failure. However, treatment options to protect the heart and the kidney in transplant recipients are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are novel anti-diabetic drugs which not only lower blood sugar, but also lower blood pressure in the kidney's individual filtering units and protect kidney function in the long term. It is unclear if the protective mechanisms of these drugs also occur in people with a kidney transplant. Several smaller studies have shown that SGLT2 inhibitors or GLP-1RA used alone are safe in people with kidney transplants. No studies have yet to look at the combined use of SGLT2 inhibitors and GLP-1RA in kidney transplant recipients (KTR).

The purpose of the HALLMARK study is to determine the mechanisms and safety of the combination use of semaglutide, a GLP-1RA, and dapagliflozin, a SGLT2 inhibitor. To investigate this, 20 kidney transplant recipients with and without diabetes will be treated with both semaglutide or dapagliflozin for 12 weeks followed by a combination of semaglutide and dapagliflozin for 12 weeks. The study will measure salt and water removal as well as the effect on blood pressure, kidney function, heart function, liver stiffness as well as the safety of these agents.

Conditions

Kidney Transplant Recipients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Semaglutide

Semaglutide Subcutaneous 0.25mg once weekly for 4 weeks, then 0.5mg once weekly for 4 weeks, then 1mg once weekly for 4 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin 10 MG

Intervention Type: DRUG

Semaglutide subcutaneous once weekly for 12 weeks.

Semaglutide, 1.0 mg/mL

Intervention Type: DRUG

Dapagliflozin oral once daily for 12 weeks.

Dapagliflozin

Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks

Group Type: EXPERIMENTAL

Dapagliflozin 10 MG

Intervention Type: DRUG

Semaglutide subcutaneous once weekly for 12 weeks.

Semaglutide, 1.0 mg/mL

Intervention Type: DRUG

Dapagliflozin oral once daily for 12 weeks.

Interventions

Dapagliflozin 10 MG

Semaglutide subcutaneous once weekly for 12 weeks.

Intervention Type: DRUG

Semaglutide, 1.0 mg/mL

Dapagliflozin oral once daily for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

FARXIGA; OZEMPIC

Eligibility Criteria

Inclusion Criteria

• Signed and dated written informed consent.
• Patients aged ≥18 years with KTR
• >3 months post kidney transplantation
• Estimated glomerular filtration rate [eGFR] ≥20 ml/min/1.73m2
• BP <160/100 and >90/60 at screening
• Body-mass index [BMI] between 18.5-40kg/m2
• In patients with T2D or PTDM, HbA1c <12.0%;

Exclusion Criteria

• Type 1 diabetes.
• History of multi-organ transplant
• Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
• Impending need for kidney biopsy or rapid decline in eGFR within 30 days prior to screening
• Actively treated BK, CMV or EBV infection
• Recurrent pyelonephritis or need for indwelling or self-catheterization
• Prior amputation or ischemic rest pain
• Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial.
• History of pancreatitis
• Personal or family history or medullary thyroid cancer or MEN2B
• History of unstable diabetic retinopathy within 1 year prior to screening
• Use of SGLT2i or GLP-1RA within 30 days prior to screening.
• Current and frequent episodes of hypoglycemia
• Current history of DKA requiring medical intervention or hospitalization
• With current risk of volume depletion, hypotension and/or electrolyte imbalance
• With known or suspected hypersensitivity to semaglutide or related products
• Patient not able to understand and comply with study requirements, based on Investigator's judgment.
• Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome etc.).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Sunita Singh, MD, MSc, FRCPC

Clinician Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sunita Singh, MD MSc FRCPC

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto General Hospital

Locations

Toronto General Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Vesta Lai

Role: CONTACT

vesta.lai@uhn.ca

416-340-4800 ext. 8508

Facility Contacts

Vesta Lai

Role: primary

vesta.lai@uhn.ca

416-340-4800 ext. 8508

Other Identifiers

23-5050

Identifier Type: -

Identifier Source: org_study_id