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

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05254418
• Collaborator: Nashville VA Medical Center (Other)
• Enrollment: 10
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 29.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases	Drug: dulaglutide injection	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Effects of Glucagon-Like Peptide-1 Agonists on Metabolism and Ectopic Fat Deposition in Chronic Kidney Disease: A Pilot and Feasibility Study
• Actual Study Start Date: Mar 15, 2022
• Anticipated Primary Completion Date: Mar 1, 2024
• Anticipated Study Completion Date: Sep 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Changes in intermuscular fat deposition as assessed by magnetic resonance imaging (MRI). [16 weeks]

   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.

2. Changes in skeletal muscle mitochondrial function as assessed by phosphocreatine recovery time constant by 31P magnetic resonance spectroscopy (31P-MRS). [16 weeks]

   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.

3. Changes in physical performance as assessed by six-minute walk test. [16 weeks]

   Sequential six-minute walk test 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 the distance walked by the patients in a self-determined pace within six minutes will be assessed.

4. 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. [16 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University Medical Center
• Nashville VA Medical Center

Investigators

• Principal Investigator: Alp Ikizler, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alp Ikizler, Catherine McLaughlin Hakim Chair in Vascular Biology, Professor of Medicine, Director, Division of Nephrology and Hypertension, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT05254418
• Other Study ID Numbers: 220057
• First Posted: Feb 24, 2022
• Last Update Posted: Apr 1, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Alp Ikizler, Catherine McLaughlin Hakim Chair in Vascular Biology, Professor of Medicine, Director, Division of Nephrology and Hypertension, Vanderbilt University Medical Center: Chronic Kidney Disease; Intermuscular fat deposition; Glucagon-like peptide-1 agonist; Insulin resistance; Mitochondrial function
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Dulaglutide

Study Results

No Results Posted as of Apr 1, 2022