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

Phase 4

Terminated

Conditions: Human Immunodeficiency Virus Infection
Diabetes Mellitus

Interventions: Drug: extended-release exenatide

Registration Number: NCT01791465

Lead Sponsor: Vanderbilt University

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bydureon treatment	extended-release exenatide	Treatment for 16 weeks with extended-release Exenatide (Bydureon)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Serum Triglycerides Levels at Baseline and 16 Weeks	baseline and 16 weeks
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	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.
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 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