GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This project investigates the anti-obesity mechanisms of glucagon-like peptide-1 (GLP-1) analogs, which are used in the treatment of human obesity and diabetes mellitus. The investigators will test if GLP-1 induces secretion of interleukin-6 (IL-6), a cytokine that may collaborate with GLP-1 analogs to induce the formation of brown fat, which has anti-diabetic properties. The results will guide future obesity and diabetes mellitus therapies.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Texas Health Science Center, Houston
• Treatments: Dulaglutide; Hydroxocobalamin; Vitamin B 12

Criteria

Inclusion criteria:

1. Men and women, ages 18-50 years

2. Diagnosis of prediabetes or at risk for prediabetes - defined as either impaired fasting glucose (fasting glucose of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of 140-199 mg/dL after 75-gram oral glucose challenge), and/or a hemoglobin A1C ranging from 5.5% to 6.4%.

3. BMI ≤ 35 kg/m2

4. Women of childbearing age must agree to use an acceptable method of pregnancy prevention (barrier methods, abstinence, or surgical sterilization) for the duration of the study

5. Patients must have the following laboratory values: Hematocrit ≥ 34 vol%, estimated glomerular filtration rate ≥ 60 mL/min per 1.73 m2, AST (SGOT) < 2.5 times ULN, ALT (SGPT) < 2.5 times ULN, alkaline phosphatase < 2.5 times ULN

6. If patients are receiving antihypertensive medications (other than beta blockers) and/or lipid-lowering medications, they must remain on stable doses for the duration of the study.

7. If patients are receiving NSAIDs or antioxidant vitamins, these must be discontinued one week prior to study initiation and cannot be restarted during the study.

8. If patient takes thyroid medications, these must be dosed to control hypo- or hyperthyroidism.

Exclusion Criteria:

1. History of Type 1 or Type 2 diabetes mellitus

2. Pregnant or breastfeeding women

3. Medications: Beta blockers, corticosteroids, monoamine oxidase inhibitors, diabetes medications (including incretin mimetics and thiazolidinediones), hormonal therapy, and/or immunosuppressive therapy over the last 2 months.

4. Uncontrolled hypo- or hyperthyroidism

5. Current tobacco use

6. Active malignancy

7. History of clinically significant cardiac, hepatic, or renal disease.

8. History of any serious hypersensitivity reaction to study medications, any other incretin mimetic, any other formulation of supplemental vitamin B12, and/or cobalt

9. Personal or family history of Leber hereditary optic nerve atrophy

10. Prisoners or subjects who are involuntarily incarcerated

11. Compulsorily detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness

12. Prior history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN 2)

13. Serum vitamin B12 level above the upper limit of assay detection