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

Chronic Kidney Diseases Clinical Trial

— GLIMP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05254418
• Other study ID #: 220057
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 15, 2022
• Est. completion date: September 1, 2024

Study information

• Verified date: May 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7
• Est. completion date: September 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	Nashville VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	16 weeks
Primary	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
Primary	Changes in physical performance as assessed by six-minute walk test.	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.	16 weeks
Primary	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