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

Phase 2

Completed

Conditions: Chronic Kidney Diseases

Interventions: Drug: dulaglutide injection

Registration Number: NCT05254418

Lead Sponsor: Vanderbilt University Medical Center

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
dulagutide arm	dulaglutide injection	Patient will receive 1.5 mg injections per week for 12 weeks.

Primary Outcome Measures

Name	Time	Method
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. 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.
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.
Changes in Physical Performance as Assessed by Systemic Physical Performance Battery Test	16 weeks	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)
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.