Clinical trial NCT01791465: Pilot Study of Bydureon to Treat Diabetes in HIV-infected Adults
Official title: Pilot Study of Extended-release Exenatide to Improve Glucose Control and Reduce Systemic Inflammation in Diabetic, HIV-infected Adults on Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus Infection
Diabetes Mellitus
Keywords: HIV
Diabetes
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2013-02-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
Secondary outcomes:
measure: Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Adipokine Leptin Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Body Mass Index at Baseline and 16 Weeks
timeFrame: 16 weeks
measure: Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Soluble CD14 Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Triglycerides Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum Total Cholesterol Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum HDL Cholesterol Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Serum LDL Cholesterol Levels at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Body Weight at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Waist Circumference at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Hip Circumference at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
measure: Waist to Hip Ratio at Baseline and 16 Weeks
timeFrame: baseline and 16 weeks
Other outcomes:
measure: 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
timeFrame: baseline and 16 weeks
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University School of Medicine
name: John Koethe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University School of Medicine
name: C. William Wester, MD
role: PRINCIPAL_INVESTIGATOR
References: