Diabetes Mellitus, Type 2Sema-RMANCT06555146
Semaglutide's Effect on Renal Hemodynamics and Function in Patients With Type 2 Diabetes Mellitus and Nephropathy
A study testing Semaglutide, 0.5 mg/mL in people with Diabetes Mellitus, Type 2 and Kidney Disease, Chronic, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
The goal of this double-blinded, placebo-controlled, randomized, crossover study is to examine the effect of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on renal hemodynamics and function in patients with type 2 diabetes mellitus (T2DM) and moderate chronic kidney disease (CKD). Read more about this study
- Who is it for?
- Ages 20 to 60 years, men only
- Conditions the study is for
- Diabetes Mellitus, Type 2, Kidney Disease, Chronic
- What is being tested?
- Semaglutide, 0.5 mg/mL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2024to Mar 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 20 to 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Type 2 diabetes mellitus diagnosed through either HbA1c ≥6,5% but ≤8,5%, or <6,5% combined with either fasting plasma glucose ≥7,0 mmol/L or plasma glucose ≥11,1 mmol/L two hours after an oral glucose tolerance test (OGTT).
- Estimated glomerular filtration rate (eGFR, CKD-EPI) between 30-60 mL/min/1.73m2
- Urine Albumin:Creatinine ratio (UACR) ≥30mg/g
- Stable RAAS blockade (ACE inhibitors or angiotensin II receptor blocker (ARB) with stable dosis for 4 weeks prior to screening)
- Discontinuation of treatment with selective sodium glucose transporter inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP-4i), GLP-1R analogs, rapid-acting and mix insulin 30 days before screening.
Who cannot join
- Immunosuppressive therapy within 30 days of screening
- Alcohol abuse
- Medical treatment with glucocorticoids
- Kidney transplantation
- Treatment for renal failure with dialysis
- Myocardial infarction within 3 months of screening
Show all 14Show fewer
- Heart failure (NYHA 3-4)
- Dysregulated arterial hypertension (systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
- Liver disease (ALAT >2 x normal value)
- Conditions which may interfere with the glucose metabolism according to the PI
- Severe claustrophobia
- Elements incompatible with MRI
- Abnormal kidney size and/or position
- Venous and arterial anatomy hindering catheterization.
Trial locations and contacts
1 site in 1 country.
Ali Asmar, MD, PhD contact
Denmark1 site
Bispebjerg Hospital, Department of Clinical Physiology & Nuclear Medicine
Copenhagen, Capital Region, 2400
Peter Sørensen, MD, +4530516279, peter.soerensen@regionh.dk
Ali Asmar, MD, PhD, ali.asmar@regionh.dk
About this study
Official title: Glucagon-like Peptide-1's Effect on Renal Regional Blood Flow and the Renal Function in Patients With Type 2 Diabetes Mellitus
The goal of this double-blinded, placebo-controlled, randomized, crossover study is to examine the effect of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on renal hemodynamics and function in patients with type 2 diabetes mellitus (T2DM) and moderate chronic kidney disease (CKD).
The study will determine the effects of semaglutide on:
- Renal arterial blood flow, regional renal perfusion, and oxygenation
- Activity of the renin-angiotensin-aldosterone system (RAAS)
- The glomerular filtration rate (GFR)
- Sodium excretion in urine
- Blood pressure and heart rate
Read the detailed description
Mechanistic studies conducted in healthy humans demonstrate a Glucagon-like peptide-1 (GLP-1)-mediated gut-kidney crosstalk. The expansion of extracellular fluid volume uncovers a natriuretic action of GLP-1. This feed-forward natriuretic system is associated with high renal extraction of GLP-1, suppression in circulating angiotensin II levels, and increased renal medullary and cortical perfusion and oxygenation. Besides potent glucose-lowering actions, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve body weight, blood pressure, and dyslipidemia, and cardiovascular and renal outcome trials demonstrate beneficial actions of GLP-1RAs used in patients with type 2 diabetes mellitus (T2DM).
Thus the beneficial cardiovascular effects of GLP-1 may partly be related to renoprotection and might represent the restoration of the gut-kidney crosstalk.
The aim of the present study is to investigate possible mechanisms behind the renal effects of semaglutide in patients with type 2 diabetes mellitus and moderate chronic kidney disease.
This is a double-blinded, placebo-controlled, crossover study and patients will participate in two independent and randomized study periods with a washout period of around 4 weeks in between.
Fifteen male participants with type 2 diabetes mellitus in the age group 20-60 years are screened, randomized, and expected to complete the present study. Informed consent is obtained before the screening meeting followed by a 30-day run-in period prior to study days.
The two study periods each extend over 8 days, where all participants consume a controlled diet with fixed salt intake corresponding to a daily intake of 50-70 mmol + 2 mmol/kg sodium for 7 days. On the fourth day before each of the two baseline trials, 24-hour urine collection will be performed. Throughout the 7 days, water intake will be ad libitum and physical activity will not be allowed.
Each period consists of Baseline day (day 5) and Intervention day (day 8)
Renal flow, perfusion, and oxygenation are measured on both days, using multiparametric MRI.
Glomerular filtration rate (GFR) is measured, using Tc99m-Diethylenetriamine pentaacetic acid (DTPA) plasma clearance.
After conducting the baseline study, the participant is given a subcutaneous injection of either semaglutide or placebo.
During the intervention study, MRI is followed by catheterization of a renal vein via the femoral vein (the Seldinger technique) for blood sampling.
- Conditions
- Diabetes Mellitus, Type 2, Kidney Disease, Chronic
- Being tested
- Semaglutide, 0.5 mg/mL, Placebo, Saline
- Keywords
- Renal flow, Regional renal perfusion, Sodium excretion in urine, Renin angiotensin aldosterone system, Glomerular filtration rate
- Medical subject headings
- Diabetes Mellitus, Type 2, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide, 0.5 mg/mLDrug
1 subcutaneous injection on baseline day
Placebo, SalineDrug
1 subcutaneous injection on baseline day
| Study group | Role | What they receive |
|---|---|---|
| Randomized to start with Semaglutide intervention in study period 1 | Other | Placebo will be given in study period 2 Receives: Drug: Semaglutide, 0.5 mg/mL; Drug: Placebo, Saline |
| Randomized to start with Placebo intervention in study period 1 | Other | Semaglutide will be given in study period 2 Receives: Drug: Semaglutide, 0.5 mg/mL; Drug: Placebo, Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total blood flow
Volume of blood per unit time, ml/min
Measured: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year).
Regional renal perfusion
volume of blood per unit time per unit tissue mass, ml/min/g
Measured: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year)
Secondary outcomes (5)
Glomerular filtration rate
Volume per unit time, ml/min
Measured: Measured with Tec99-DTPA clearance. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year)
Sodium excretion in urine
Concentration, mmol/l
Measured: One measurement will be done on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year)
Activation of the renin angiotensin aldosterone system
Concentration, mmol/l
Measured: Blood samples will be taken 3 times on each intervention day, a total of 6 measurements for each participant, over the span of the study (approximately 1 year)
Blood pressure
mmhg
Measured: Measured continuously during a 60 minute period on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year)
Heart Rate
Beats pr. minute
Measured: Measured continuously during a 60 minute period on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2024
- Study startAug 2024 (estimated)
- Primary completionMar 2025 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blinded, placebo-controlled crossover with around 4 weeks between study periods.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ali Asmar, Bispebjerg Hospital
- Investigators
- Ali Asmar, MD, PhD, Principal investigator, Bispebjerg Hospital, Department of Clinical Physiology & Nuclear Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06555146
- Sponsor's protocol ID
- H-20036378
- Acronym
- Sema-RMA
- Status last verified
- Aug 2024
- First submitted
- 7 Aug 2024
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
PubMed 39963952
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucagon-like Peptide-1's Effect on Renal Regional Blood Flow and the Renal Function in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT06555146
- Acronym / sponsor ID
- Sema-RMA / H-20036378
- Conditions
- Diabetes Mellitus, Type 2, Kidney Disease, Chronic
- Keywords
- Renal flow, Regional renal perfusion, Sodium excretion in urine, Renin angiotensin aldosterone system, Glomerular filtration rate
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Study start
- Aug 2024 (estimated)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 15 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this double-blinded, placebo-controlled, randomized, crossover study is to examine the effect of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on renal hemodynamics and function in patients with type 2 diabetes mellitus (T2DM) and moderate chronic kidney disease (CKD).
The study will determine the effects of semaglutide on:
- Renal arterial blood flow, regional renal perfusion, and oxygenation
- Activity of the renin-angiotensin-aldosterone system (RAAS)
- The glomerular filtration rate (GFR)
- Sodium excretion in urine
- Blood pressure and heart rate
Detailed description
Mechanistic studies conducted in healthy humans demonstrate a Glucagon-like peptide-1 (GLP-1)-mediated gut-kidney crosstalk. The expansion of extracellular fluid volume uncovers a natriuretic action of GLP-1. This feed-forward natriuretic system is associated with high renal extraction of GLP-1, suppression in circulating angiotensin II levels, and increased renal medullary and cortical perfusion and oxygenation. Besides potent glucose-lowering actions, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve body weight, blood pressure, and dyslipidemia, and cardiovascular and renal outcome trials demonstrate beneficial actions of GLP-1RAs used in patients with type 2 diabetes mellitus (T2DM).
Thus the beneficial cardiovascular effects of GLP-1 may partly be related to renoprotection and might represent the restoration of the gut-kidney crosstalk.
The aim of the present study is to investigate possible mechanisms behind the renal effects of semaglutide in patients with type 2 diabetes mellitus and moderate chronic kidney disease.
This is a double-blinded, placebo-controlled, crossover study and patients will participate in two independent and randomized study periods with a washout period of around 4 weeks in between.
Fifteen male participants with type 2 diabetes mellitus in the age group 20-60 years are screened, randomized, and expected to complete the present study. Informed consent is obtained before the screening meeting followed by a 30-day run-in period prior to study days.
The two study periods each extend over 8 days, where all participants consume a controlled diet with fixed salt intake corresponding to a daily intake of 50-70 mmol + 2 mmol/kg sodium for 7 days. On the fourth day before each of the two baseline trials, 24-hour urine collection will be performed. Throughout the 7 days, water intake will be ad libitum and physical activity will not be allowed.
Each period consists of Baseline day (day 5) and Intervention day (day 8)
Renal flow, perfusion, and oxygenation are measured on both days, using multiparametric MRI.
Glomerular filtration rate (GFR) is measured, using Tc99m-Diethylenetriamine pentaacetic acid (DTPA) plasma clearance.
After conducting the baseline study, the participant is given a subcutaneous injection of either semaglutide or placebo.
During the intervention study, MRI is followed by catheterization of a renal vein via the femoral vein (the Seldinger technique) for blood sampling.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, double-blinded, placebo-controlled crossover with around 4 weeks between study periods.
| Arm | Type | Receives |
|---|---|---|
| Randomized to start with Semaglutide intervention in study period 1 | Other | Drug: Semaglutide, 0.5 mg/mL, Drug: Placebo, SalinePlacebo will be given in study period 2 |
| Randomized to start with Placebo intervention in study period 1 | Other | Drug: Semaglutide, 0.5 mg/mL, Drug: Placebo, SalineSemaglutide will be given in study period 2 |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Type 2 diabetes mellitus diagnosed through either HbA1c ≥6,5% but ≤8,5%, or <6,5% combined with either fasting plasma glucose ≥7,0 mmol/L or plasma glucose ≥11,1 mmol/L two hours after an oral glucose tolerance test (OGTT).
- Estimated glomerular filtration rate (eGFR, CKD-EPI) between 30-60 mL/min/1.73m2
- Urine Albumin:Creatinine ratio (UACR) ≥30mg/g
- Stable RAAS blockade (ACE inhibitors or angiotensin II receptor blocker (ARB) with stable dosis for 4 weeks prior to screening)
- Discontinuation of treatment with selective sodium glucose transporter inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP-4i), GLP-1R analogs, rapid-acting and mix insulin 30 days before screening.
Key exclusion criteria (14 listed)
- Immunosuppressive therapy within 30 days of screening
- Alcohol abuse
- Medical treatment with glucocorticoids
- Kidney transplantation
- Treatment for renal failure with dialysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide, 0.5 mg/mL1 subcutaneous injection on baseline day | Drug | Randomized to start with Placebo intervention in study period 1, Randomized to start with Semaglutide intervention in study period 1 |
| Placebo, Saline1 subcutaneous injection on baseline day | Drug | Randomized to start with Placebo intervention in study period 1, Randomized to start with Semaglutide intervention in study period 1 |
Primary outcome
Total blood flow
Time frame: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year).
Volume of blood per unit time, ml/min
Regional renal perfusion
Time frame: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year)
volume of blood per unit time per unit tissue mass, ml/min/g
5 secondary outcomes
Glomerular filtration rate
Time frame: Measured with Tec99-DTPA clearance. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year)
Sodium excretion in urine
Time frame: One measurement will be done on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year)
Activation of the renin angiotensin aldosterone system
Time frame: Blood samples will be taken 3 times on each intervention day, a total of 6 measurements for each participant, over the span of the study (approximately 1 year)
Blood pressure
Time frame: Measured continuously during a 60 minute period on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year)
Heart Rate
Time frame: Measured continuously during a 60 minute period on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Derived from this study: PubMed 39963952Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ali Asmar, MD, PhD contact
Ali Asmar, MD, PhD principal investigator
Bispebjerg Hospital, Department of Clinical Physiology & Nuclear Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Semaglutide, 0.5 mg/mL in people with Diabetes Mellitus, Type 2 and Kidney Disease, Chronic, run by Bispebjerg Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter Sørensen, MD (+4530516279, peter.soerensen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total blood flow (time frame: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06555146, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2024; AzTrials last refreshed its copy on 3 Nov 2026.