Kidney Transplant RecipientsPhase 2HALLMARKNCT05938712
The Efficacy, Mechanism & Safety of Sodium Glucose Co-Transporter-2 Inhibitor & Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Kidney Transplant Recipients
A Phase 2 study testing Dapagliflozin 10 MG and Semaglutide, 1.0 mg/mL in people with Kidney Transplant Recipients, run by University Health Network, Toronto at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant Recipients
- What is being tested?
- Dapagliflozin 10 MG and Semaglutide, 1.0 mg/mL
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 24 Oct 2023to 1 Mar 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%;
Who cannot join
- 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
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- 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.).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Toronto General Hospital
Toronto, Ontario, M5G 2N2
Vesta Lai, 416-340-4800 ext. 8508, vesta.lai@uhn.ca
About this study
Official title: 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
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.
Read the 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
- Being tested
- Dapagliflozin 10 MG, Semaglutide, 1.0 mg/mL
- Keywords
- Type 2 diabetes, SGLT2 inhibition, GLP-1 receptor agonist
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10 MGDrug
Also called FARXIGA
Semaglutide subcutaneous once weekly for 12 weeks.
Semaglutide, 1.0 mg/mLDrug
Also called OZEMPIC
Dapagliflozin oral once daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Semaglutide Subcutaneous 0.25mg once weekly for 4 weeks, then 0.5mg once weekly for 4 weeks, then 1mg once weekly for 4 weeks. Receives: Drug: Dapagliflozin 10 MG; Drug: Semaglutide, 1.0 mg/mL |
| Dapagliflozin | Experimental | Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks Receives: Drug: Dapagliflozin 10 MG; Drug: Semaglutide, 1.0 mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proximal tubular natriuresis with combination therapy
Measured by fractional excretion of sodium
Measured: From baseline to combination therapy end (24 weeks)
Proximal tubular natriuresis with monotherapy
Measured by fractional excretion of sodium
Measured: From baseline to monotherapy end (12 weeks)
Secondary outcomes (19)
Measured Glomerular Filtration Rate
GFR, based on plasma iohexol clearance
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Estimated Glomerular Filtration Rate
GFR, based on serum creatinine
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration
Using ELISA
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Urinary albumin excretion
From 24-hour urine collection
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Arterial stiffness
Measured using a Sphygmocor device
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Liver stiffness
Using transient elastography
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Diastolic function
Using 2D echocardiography
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in percentage of glycated hemoglobin (HbA1c)
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in concentration of urine glucose excretion
Urinary analysis will be performed to quantify the amount of glucose excretion.
Measured: 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)
Bioimpedence measurements will be taken to study the effects of intervention on body composition.
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Change in body weight
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: the incidence of acute kidney injury.
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: the incidence of hypotension
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of hyperkalemia
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of urinary and mycotic infections.
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The number of ketoacidosis events.
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of amputations.
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The incidence of pancreatitis or biliary complications
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Safety: The number of allergic reaction events.
Measured: From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2023
- Study start24 Oct 2023
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant RecipientsStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Patients will be allocated to treatment with either dapagliflozin 10 mg PO daily alone for 12 weeks or subcutaneous once weekly semaglutide up-titrated as tolerated every 4 weeks starting with 0.25 mg, then to 0.5 mg to 1 mg alone for 12 weeks, followed by a subsequent treatment period of combination therapy with dapagliflozin 10 mg PO daily plus maximally tolerated dose semaglutide (up-titrated every 4 weeks from 0.25 mg to 0.5 mg to 1 mg) subcutaneous once weekly.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sunita Singh, MD, MSc, FRCPC, University Health Network, Toronto
- Investigators
- Sunita Singh, MD MSc FRCPC, Principal investigator, University Health Network, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05938712
- Sponsor's protocol ID
- 23-5050
- Acronym
- HALLMARK
- Status last verified
- Apr 2026
- First submitted
- 16 May 2023
- Last updated
- 1 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No