Pilot Study of Bydureon to Treat Diabetes in HIV-infected Adults

Pilot Study of Extended-release Exenatide to Improve Glucose Control and Reduce Systemic Inflammation in Diabetic, HIV-infected Adults on Antiretroviral Therapy

Sponsors

Lead Sponsor: Vanderbilt University

Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)

Source Vanderbilt University Medical Center
Brief Summary

This pilot study will evaluate the effects of the anti-diabetic drug Bydureon (exenatide extended-release formulation) on blood sugar levels and serum markers of inflammation in a cohort of 12 HIV-infected adults on combination antiretroviral therapy (cART) with untreated diabetes mellitus. Previous studies have shown that high levels of persistent systemic inflammation predict the development of cardiovascular and metabolic diseases in HIV-infected persons on cART (a group at very high risk of atherosclerosis and myocardial infarction). Bydureon has demonstrated potent anti-inflammatory effects in prior studies of non-HIV infected persons, which suggests that this agent may represent a unique and preferred medication for the treatment of insulin resistance in HIV-infected adults. The Investigators hypothesize that short-term (16 weeks) therapy with Bydureon will improve glucose tolerance and significantly reduce circulating plasma levels of interleukin-6 (IL-6) and highly-sensitive C-reactive protein (hsCRP), two biomarkers strongly implicated in the development of cardiovascular and metabolic diseases in diabetic, HIV-infected, cART-treated adults.

Detailed Description

No further information. This was a single-arm trial to add an additional anti-diabetic medication to patients already known to be diabetic. The primary endpoint assessed whether the intervention reduced inflammation. There was no control arm.

Overall Status Terminated
Start Date March 2013
Completion Date December 2014
Primary Completion Date December 2014
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks baseline and 16 weeks
Secondary Outcome
Measure Time Frame
Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks baseline and 16 weeks
Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks baseline and 16 weeks
Serum Adipokine Leptin Levels at Baseline and 16 Weeks baseline and 16 weeks
Body Mass Index at Baseline and 16 Weeks 16 weeks
Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Soluble CD14 Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Triglycerides Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum Total Cholesterol Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum HDL Cholesterol Levels at Baseline and 16 Weeks baseline and 16 weeks
Serum LDL Cholesterol Levels at Baseline and 16 Weeks baseline and 16 weeks
Body Weight at Baseline and 16 Weeks baseline and 16 weeks
Waist Circumference at Baseline and 16 Weeks baseline and 16 weeks
Hip Circumference at Baseline and 16 Weeks baseline and 16 weeks
Waist to Hip Ratio at Baseline and 16 Weeks baseline and 16 weeks
Enrollment 6
Condition
Intervention

Intervention Type: Drug

Intervention Name: extended-release exenatide

Description: Single arm study - 2mg Bydureon every 7 days x 16 weeks

Arm Group Label: Bydureon treatment

Other Name: Bydureon

Eligibility

Criteria:

Inclusion Criteria:

- Age ≥ 18 years

- Body mass index ≥ 25 kg/m2

- Glycosylated hemoglobin (A1C) value ≥ 6.5% OR having a fasting blood glucose ≥ 126 mg/dL

- On stable antiretroviral therapy for ≥ 12 months (with a fully suppressed plasma HIV-1 RNA level)

- Negative serum pregnancy test (females only)

Exclusion Criteria:

- History of pancreatitis

- Screening serum lipase value greater than or equal to 2 times the upper limit of normal (≥ 420 U/L)

- History of pancreatic cancer or thyroid cancer in patient, a first-degree relative, or a grandparent

- History of Multiple Endocrine Neoplasia (MEN) 2 syndrome

- History of gastroparesis, inflammatory bowel disease, and/or other severe gastrointestinal disease

- Estimated glomerular filtration rate (eGFR) ≤ 50 mls/minute

- Documented history of hypoglycemia (blood glucose <40 mg/dl)

- Active moderate-heavy alcohol use (more than 2 drinks/day) or >4 drinks in a single 24 hour period

- On an anti-diabetic medication within 3 months of enrollment

- On an HMG-CoA reductase inhibitor (statin) within 3 months of enrollment

- Persons on a didanosine (ddI) and/or stavudine (d4T)-containing cART (due to the heightened risk of pancreatitis)

Gender: All

Minimum Age: 18 Years

Maximum Age: 99 Years

Healthy Volunteers: No

Overall Official
Location
Facility: Vanderbilt University
Location Countries

United States

Verification Date

January 2017

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Vanderbilt University

Investigator Full Name: John R. Koethe

Investigator Title: Assistant Professor of Medicine

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Bydureon treatment

Type: Experimental

Description: Treatment for 16 weeks with extended-release Exenatide (Bydureon)

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov