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

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01791465
• Other study ID #: 121342
• Secondary ID: P30AI054999
• Status: Completed
• Phase: Phase 4
• First received: February 11, 2013
• Last updated: December 19, 2014
• Start date: March 2013
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Diabetes Mellitus
• HIV Infections
• Human Immunodeficiency Virus Infection
• Immunologic Deficiency Syndromes
• Virus Diseases

Intervention

Drug:
• extended-release exenatide

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The change from baseline to 16 weeks in peripheral endothelial tonography, as measured by the non-invasive EndoPAT system		16 weeks	No
Primary	Change in serum interleukin 6 (IL-6) and highly-sensitive C-reactive protein (hsCRP) levels	The primary outcome will be the change in serum IL-6 and hsCRP levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment.	16 weeks	No
Secondary	Change from baseline to 16 weeks in serum levels of soluble tumor necrosis factor alpha (TNF-a) receptor 1 & 2, cystatin C, macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1a), and interleukin 1 beta (IL-1ß)		16 weeks	No
Secondary	The change from baseline to 16 weeks in the response to an oral glucose tolerance challenge and in serum hemoglobin A1c levels		16 weeks	No
Secondary	The change from baseline to 16 weeks in serum LDL cholesterol, HDL cholesterol, total cholesterol, & triglycerides		16 weeks	No
Secondary	The change from baseline to 16 weeks in serum adipokine (leptin and adiponectin) levels		16 weeks	No
Secondary	The change from baseline to 16 weeks in body fat mass and distribution, anthropometrics, and body mass index		16 weeks	No