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

Primary Purpose

Chronic Kidney Diseases

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
dulaglutide injection
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Chronic Kidney Diseases focused on measuring Chronic Kidney Disease, Intermuscular fat deposition, Glucagon-like peptide-1 agonist, Insulin resistance, Mitochondrial function

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Vanderbilt University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

dulagutide arm

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
February 1, 2022
Last Updated
April 28, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
Nashville VA Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05254418
Brief Title
Effects of GLP1-RA on Ectopic Fat Deposition in Chronic Kidney Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2022 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
September 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
Nashville VA Medical Center

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases
Keywords
Chronic Kidney Disease, Intermuscular fat deposition, Glucagon-like peptide-1 agonist, Insulin resistance, Mitochondrial function

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
dulagutide arm
Arm Type
Experimental
Arm Description
Patient will receive 1.5 mg injections per week for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
dulaglutide injection
Intervention Description
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
Primary Outcome Measure Information:
Title
Changes in intermuscular fat deposition as assessed by magnetic resonance imaging (MRI).
Description
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.
Time Frame
16 weeks
Title
Changes in skeletal muscle mitochondrial function as assessed by phosphocreatine recovery time constant by 31P magnetic resonance spectroscopy (31P-MRS).
Description
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.
Time Frame
16 weeks
Title
Changes in physical performance as assessed by six-minute walk test.
Description
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.
Time Frame
16 weeks
Title
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.
Description
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.
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alp Ikizler, MD
Phone
615-343-6104
Email
alp.ikizler@vumc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Tiffany Bess, MA
Phone
615-343-8296
Email
tiffany.bess@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alp Ikizler, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Talat A Ikizler
Phone
615-343-6104
Email
alp.ikizler@vumc.org
First Name & Middle Initial & Last Name & Degree
Tiffany Bess
Email
tiffany.bess@vumc.org

12. IPD Sharing Statement

Plan to Share IPD
No

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

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