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

NCT01791465 | Terminated Phase 4 Results

• 2 other identifiers: 121342P30AI054999
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus Infection; Diabetes Mellitus

Keywords

HIV; Diabetes

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (18)

• 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

Other Outcomes (1)

• 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

  baseline and 16 weeks

Study Arms (1)

Bydureon treatment

EXPERIMENTAL

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

Drug: extended-release exenatide

Interventions

extended-release exenatide DRUG

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

Also known as: Bydureon

Bydureon treatment

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vanderbilt University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37240, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Diabetes Mellitus

Interventions

Exenatide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Limitations and Caveats

Trial terminated after only 6 individuals enrolled due to lack of interest in participation from patients and expiration of funding. Results are not considered reliable due to low number of observations

Results Point of Contact

• Title: John Koethe MD
• Organization: Vanderbilt University Medical Center

john.r.koethe@vanderbilt.edu

615-343-0533

Study Officials

• John Koethe, MD

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

• C. William Wester, MD

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: February 15, 2013
• Study Start: March 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 10, 2017
• Results First Posted: March 10, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)