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

This study has been terminated.
(This study was terminated after 6 patients due to loss of funding)
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
John R. Koethe, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01791465
First received: February 11, 2013
Last updated: January 20, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Human Immunodeficiency Virus Infection
Diabetes Mellitus
Drug: extended-release exenatide
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Pilot Study of Extended-release Exenatide to Improve Glucose Control and Reduce Systemic Inflammation in Diabetic, HIV-infected Adults on Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by John R. Koethe, Vanderbilt University:

Primary Outcome Measures:
  • Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks [ Time Frame: 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 [ Time Frame: 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:
  • Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks [ Time Frame: 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 [ Time Frame: baseline and 16 weeks ]
  • Body Mass Index at Baseline and 16 Weeks [ Time Frame: 16 weeks ]
  • Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum Soluble CD14 Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum Triglycerides Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum Total Cholesterol Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum HDL Cholesterol Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Serum LDL Cholesterol Levels at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Body Weight at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Waist Circumference at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Hip Circumference at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]
  • Waist to Hip Ratio at Baseline and 16 Weeks [ Time Frame: baseline and 16 weeks ]

Other Outcome Measures:
  • 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 [ Time Frame: baseline and 16 weeks ]
    Normal: LnRHI > 0.51 Abnormal: LnRHI ≤ 0.51


Enrollment: 6
Study Start Date: March 2013
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Bydureon

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

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01791465

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37240
Sponsors and Collaborators
Vanderbilt University
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
  More Information

Responsible Party: John R. Koethe, Assistant Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01791465     History of Changes
Other Study ID Numbers: 121342
P30AI054999 ( US NIH Grant/Contract Award Number )
Study First Received: February 11, 2013
Results First Received: May 5, 2016
Last Updated: January 20, 2017
Individual Participant Data  
Plan to Share IPD: No
Plan Description: Individual participant data is protected by HIPPA and Vanderbilt University research regulations. Summary de-identified data is available if requested

Keywords provided by John R. Koethe, Vanderbilt University:
HIV
Diabetes

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Diabetes Mellitus
Immunologic Deficiency Syndromes
Virus Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on May 25, 2017