Effects of GLP1-RA on Ectopic Fat Deposition in Chronic Kidney Disease

NCT05254418 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 220057
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic kidney disease (CKD) is a burden of morbidity and mortality. Increased protein breakdown in skeletal muscle (wasting) and ectopic fat deposition are important determinants of poor clinical outcome in patient with CKD. Insulin resistance plays a critical role in skeletal muscle wasting and ectopic fat deposition. Glucagon-like peptide-1 receptor agonists (GLP-1RA) decrease ectopic fat deposition in patients with type 2 diabetes, prediabetes, obese and overweight subjects. The influence of GLP-1RA on ectopic fat deposition in CKD patients in unknown. The investigators' will test the hypothesis that GLP-1RA decreases intermuscular (ectopic) fat deposition in patients with stage 3-4 CKD. The investigators' will do so by addressing the following specific aims: Specific Aim 1: To test the hypothesis that GLP-1RA decreases intermuscular fat deposition in patients with stage 3-4 CKD. Specific Aim 2: To test the hypothesis that GLP-1RA improves skeletal muscle mitochondrial function in patients with stage 3-4 CKD. Specific Aim 3: To test the hypothesis that GLP-1RA improves physical performance in patients with stage 3-4 CKD. Specific Aim 4: To test the safety and feasibility of 12 weeks of dulaglutide 1.5 mg/wk administration as an adjunct therapy to the standard care of patients with stage 3-4 CKD.

Conditions

Chronic Kidney Diseases

Keywords

Chronic Kidney Disease; Intermuscular fat deposition; Glucagon-like peptide-1 agonist; Insulin resistance; Mitochondrial function

Outcome Measures

Primary Outcomes (4)

• Changes in Intermuscular Fat Deposition as Assessed by Magnetic Resonance Imaging (MRI).

  Sequential MRI will be performed during the run-in phase, at the beginning and end of the dulaglutide treatment and at the end of the observational follow up period. Intermuscular fat will be calculated as the ratio between intermuscular fat and muscle volumes in the mid-thigh region. Changes in intermuscular fat deposition will be calculated. the reported value is the difference between the end of study and baseline values (end of study minus baseline). A negative value will reflect a decrease in IMAT.

  16 weeks

• Changes in Skeletal Muscle Mitochondrial Function as Assessed by Phosphocreatine Recovery Time Constant by 31P Magnetic Resonance Spectroscopy (31P-MRS).

  Sequential 31P-MRS, a gold standard technique for muscle mitochondrial function assessment, will be performed during the run-in phase, at the beginning and end of the dulaglutide treatment and at the end of the observational follow up period. Changes in phosphocreatine recovery time constant will be assessed.

  16 weeks

• Changes in Physical Performance as Assessed by Systemic Physical Performance Battery Test

  Systemic physical performance battery test will be performed at the beginning and end of the dulaglutide treatment period. Changes will be assessed. The total score that will be reported is calculated by adding scores obtained from Balance test, Gait speed test and Chair stand test scores. The score for the primary outcome will be the difference between baseline and end of study. The SPPB total score ranges from 0 (worst performance) to 12 points (best performance) and categorically evaluates performance in the tests using three or four classes of scores: three classes: 0-6 points (poor performance), 7-9 points (moderate performance), and 10-12 points (good performance); or four classes: 0-3 points (disability/very poor performance), 4-6 points (poor performance), 7-9 points (moderate performance), and 10-12 points (good performance)

  16 weeks

• Safety and Feasibility of Dulaglutide Treatment as Evaluated by Subject Interview, Continuous Glucose Monitoring, Adverse Events (AE), Laboratory Tests, Vital Signs, ECG & Allergic/Hypersensitivity Reactions.

  An AE will be defined as any undesirable medical event occurring to a subject in a clinical trial, whether it is related to the study agent. All adverse events will be graded as follows: 0 = No adverse events or within normal limits; 1 = Mild-did not require treatment; 2 = Moderate resolved with treatment; 3 = Severe-required professional medical attention; 4 = Life-threatening or disabling; 5 = Death.

  16 weeks

Study Arms (1)

dulagutide arm

EXPERIMENTAL

Patient will receive 1.5 mg injections per week for 12 weeks.

Drug: dulaglutide injection

Interventions

dulaglutide injection DRUG

All participants will undergo a 4-week run-in phase followed by 12 weeks of treatment (dulaglutide 1.5 mg/wk), followed by 4 weeks of follow up after discontinuing the study medication

dulagutide arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with stage 3-4 CKD (eGFR 15-59 ml/min/1/73 m2)
• Age ≥ 18 years and ≤75 years

You may not qualify if:

• Patients with type 1 diabetes mellitus
• Patients with T2D who are on insulin therapy or who started a new antidiabetic medication within 1 month prior to study or who received incretin-based therapy within 3 months prior to study
• BMI \<25 kg/m2, BMI \>40 kg/m2
• HbA1c\>8% measured within 1 month prior to study, or a history of hypoglycemic episode within 1 year prior to study, or a history of diabetic ketoacidosis
• Uncontrolled hypertension (\>200/100 mmHg) despite optimal antihypertensive therapy
• Arrythmia, heart failure (NYHA class III-IV), valve disease or heart diseases other than coronary artery disease
• History of major gastrointestinal surgery, inflammatory bowel disease, pancreatitis or cholelithiasis
• Personal or family history of medullary thyroid cancer, or personal history of Multiple Endocrine Neoplasia (MEN)-2
• Pregnancy, breast feeding or intention to become pregnant
• Previous renal transplantation
• Acute or chronic infectious diseases
• Cancer or chemotherapy within 3 years prior to study
• Treatment with systemic corticosteroids within 3 months prior to study
• Known or suspected allergy to dulaglutide
• Claustrophobia or other contraindications for magnetic resonance imaging

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• VA Tennessee Valley Health Care System: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Insulin Resistance

Interventions

dulaglutide

Condition Hierarchy (Ancestors)

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; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Talat Alp Ikizler
• Organization: Vanderbilt University Medical Center

alp.ikizler@vumc.org

6159366646

Study Officials

• Alp Ikizler, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Catherine McLaughlin Hakim Chair in Vascular Biology, Professor of Medicine, Director, Division of Nephrology and Hypertension

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 24, 2022
• Study Start: March 15, 2022
• Primary Completion: May 1, 2024
• Study Completion: August 1, 2024
• Last Updated: April 20, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)