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

Effects of Glucagon-Like Peptide-1 Agonists on Metabolism and Ectopic Fat Deposition in Chronic Kidney Disease: A Pilot and Feasibility Study

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: dulaglutide injection

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Patients with type 1 diabetes mellitus
2. 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
3. BMI <25 kg/m2, BMI >40 kg/m2
4. 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
5. Uncontrolled hypertension (>200/100 mmHg) despite optimal antihypertensive therapy
6. Arrythmia, heart failure (NYHA class III-IV), valve disease or heart diseases other than coronary artery disease
7. History of major gastrointestinal surgery, inflammatory bowel disease, pancreatitis or cholelithiasis
8. Personal or family history of medullary thyroid cancer, or personal history of Multiple Endocrine Neoplasia (MEN)-2
9. Pregnancy, breast feeding or intention to become pregnant
10. Previous renal transplantation
11. Acute or chronic infectious diseases
12. Cancer or chemotherapy within 3 years prior to study
13. Treatment with systemic corticosteroids within 3 months prior to study
14. Known or suspected allergy to dulaglutide
15. Claustrophobia or other contraindications for magnetic resonance imaging

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dulagutide arm; Patient will receive 1.5 mg injections per week for 12 weeks.	Drug: dulaglutide injection; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: VA Tennessee Valley Health Care System
• Investigators: Principal Investigator: Alp Ikizler, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Actual): May 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Insulin resistance; Chronic Kidney Disease; Mitochondrial function; Glucagon-like peptide-1 agonist; Intermuscular fat deposition
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Dulaglutide
• Other Study ID Numbers: 220057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes