A Two Arm, Open Label, Pilot Study to Evaluate the Safety and Efficacy of the Combined Use of Once Daily 10mg Dapagliflozin and Once Weekly 1.0mg Semaglutide in Kidney Transplant Recipients
Overview
- Phase
- Phase 2
- Intervention
- Semaglutide, 1.0 mg/mL
- Conditions
- Kidney Transplant Recipients
- Sponsor
- University Health Network, Toronto
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Proximal tubular natriuresis with combination therapy
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Sunita Singh, MD, MSc, FRCPC
Clinician Scientist
University Health Network, Toronto
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
Arms & Interventions
Dapagliflozin
Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks
Intervention: Semaglutide, 1.0 mg/mL
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.
Intervention: Semaglutide, 1.0 mg/mL
Dapagliflozin
Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks
Intervention: Dapagliflozin 10 MG
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.
Intervention: Dapagliflozin 10 MG
Outcomes
Primary Outcomes
Proximal tubular natriuresis with combination therapy
Time Frame: From baseline to combination therapy end (24 weeks)
Measured by fractional excretion of sodium
Proximal tubular natriuresis with monotherapy
Time Frame: From baseline to monotherapy end (12 weeks)
Measured by fractional excretion of sodium
Secondary Outcomes
- Liver stiffness(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: the incidence of hypotension(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in percentage of glycated hemoglobin (HbA1c)(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in concentration of urine glucose excretion(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of urinary and mycotic infections.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: the incidence of acute kidney injury.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of amputations.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The number of allergic reaction events.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Measured Glomerular Filtration Rate(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Estimated Glomerular Filtration Rate(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Urinary albumin excretion(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Arterial stiffness(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Diastolic function(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in body composition (percent body mass, body fat, and muscle mass)(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in body weight(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of hyperkalemia(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of pancreatitis or biliary complications(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The number of ketoacidosis events.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])