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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05938712
Other study ID # 23-5050
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 24, 2023
Est. completion date October 1, 2025

Study information

Verified date July 2023
Source University Health Network, Toronto
Contact Vesta Lai
Phone 416-340-4800
Email vesta.lai@uhn.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date October 1, 2025
Est. primary completion date October 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.).

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Dapagliflozin 10 MG
Semaglutide subcutaneous once weekly for 12 weeks.
Semaglutide, 1.0 mg/mL
Dapagliflozin oral once daily for 12 weeks.

Locations

Country Name City State
Canada Toronto General Hospital Toronto Ontario

Sponsors (1)

Lead Sponsor Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proximal tubular natriuresis with combination therapy Measured by fractional excretion of sodium From baseline to combination therapy end (24 weeks)
Primary Proximal tubular natriuresis with monotherapy Measured by fractional excretion of sodium From baseline to monotherapy end (12 weeks)
Secondary Measured Glomerular Filtration Rate GFR, based on plasma iohexol clearance From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Estimated Glomerular Filtration Rate GFR, based on serum creatinine From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration Using ELISA From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Urinary albumin excretion From 24-hour urine collection From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Arterial stiffness Measured using a Sphygmocor device From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Liver stiffness Using transient elastography From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Diastolic function Using 2D echocardiography From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Change in percentage of glycated hemoglobin (HbA1c) From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Change in concentration of urine glucose excretion Urinary analysis will be performed to quantify the amount of glucose excretion. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Change in body composition (percent body mass, body fat, and muscle mass) Bioimpedence measurements will be taken to study the effects of intervention on body composition. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Change in body weight From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: the incidence of acute kidney injury. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: the incidence of hypotension From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: The incidence of hyperkalemia From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: The incidence of urinary and mycotic infections. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: The number of ketoacidosis events. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: The incidence of amputations. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: The incidence of pancreatitis or biliary complications From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Secondary Safety: The number of allergic reaction events. From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
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