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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus; Human Immunodeficiency Virus Infection
• Intervention / Treatment: Drug: extended-release exenatide

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37240
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bydureon treatment; Treatment for 16 weeks with extended-release Exenatide (Bydureon)	Drug: extended-release exenatide; Single arm study - 2mg Bydureon every 7 days x 16 weeks; Other Names: Bydureon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks	The primary outcome will be the change in hsCRP levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment.	baseline and 16 weeks
Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks	The primary outcome will be the change in serum IL-6 levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment.	baseline and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	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	The Oral Glucose Insulin Sensitivity (OGIS) is a method for the assessment of insulin sensitivity from the oral glucose tolerance test. OGIS provides an index which is analogous to the index of insulin sensitivity obtained from the glucose clamp. OGIS values for glucose clearance are reported in units of ml/min per square meter of body surface area. Lower values indicate slower glucose clearance and higher insulin resistance.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral Endothelial Tonography, as Measured by the Non-invasive EndoPAT System Using the LnRHI (Natural Log of Reactive Hyperemia Index), at Baseline and 16 Weeks	Normal: LnRHI > 0.51 Abnormal: LnRHI ≤ 0.51	baseline and 16 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: John Koethe, MD, Vanderbilt University School of Medicine; Principal Investigator: C. William Wester, MD, Vanderbilt University School of Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 11, 2013
• First Submitted That Met QC Criteria: February 13, 2013
• First Posted (Estimate): February 15, 2013

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Diabetes; HIV
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 121342; P30AI054999 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data is protected by HIPPA and Vanderbilt University research regulations. Summary de-identified data is available if requested