Semaglutide's Effect on Renal Hemodynamics and Function in Patients With Type 2 Diabetes Mellitus and Nephropathy

NCT06555146 | Not Yet Recruiting

• 1 other identifier: H-20036378
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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). 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

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

Outcome Measures

Primary Outcomes (2)

• Total blood flow

  Volume of blood per unit time, ml/min

  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 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

  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

  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

  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

  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

  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)

Study Arms (2)

Randomized to start with Semaglutide intervention in study period 1

OTHER

Placebo will be given in study period 2

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

Drug: Semaglutide, 0.5 mg/mL; Drug: Placebo, Saline

Interventions

Semaglutide, 0.5 mg/mL DRUG

1 subcutaneous injection on baseline day

Randomized to start with Placebo intervention in study period 1; Randomized to start with Semaglutide intervention in study period 1

Placebo, Saline DRUG

1 subcutaneous injection on baseline day

Randomized to start with Placebo intervention in study period 1; Randomized to start with Semaglutide intervention in study period 1

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Bispebjerg Hospital: lead

Study Sites (1)

Bispebjerg Hospital, Department of Clinical Physiology & Nuclear Medicine

Copenhagen, Capital Region, 2400, Denmark

Location

Related Publications (1)

• 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.

  PMID: 39963952 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic

Interventions

semaglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Ali Asmar, MD, PhD

  Bispebjerg Hospital, Department of Clinical Physiology & Nuclear Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Sørensen, MD

CONTACT

+4530516279; peter.soerensen@regionh.dk

Ali Asmar, MD, PhD

CONTACT

ali.asmar@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Associate Professor

Model Details: Randomized, double-blinded, placebo-controlled crossover with around 4 weeks between study periods.

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 15, 2024
• Study Start: August 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: August 15, 2024

Record last verified: 2024-08

Locations

DK (1)