Metformin for HIV Inflammation

Overview

This proposal seeks to assess the impact of 24 weeks of metformin on non-calcified plaques and calcified plaques assessed by coronary CT angiography, and on whether these changes can be explained by metformin-induced phenotypic and secretory changes of monocytes.

Full Title of Study: “Open-Label, Randomized, 24-Week Pilot Study of Metformin vs Observation for Persistent Immune Activation in Chronic HIV Infection”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 2016

Interventions

  • Drug: metformin extended release

Arms, Groups and Cohorts

  • Active Comparator: Metformin Treatment Arm
    • 500 mg metformin Extended Release tablets – one tablet daily increased at 4 weeks to 2 tablets (1000 mg) daily.
  • No Intervention: Observational Arm
    • Observation only

Clinical Trial Outcome Measures

Primary Measures

  • Coronary plaques by CT angiography
    • Time Frame: 24 weeks
    • change in total numbers of atherosclerotic plaques detected in the coronary arteries

Secondary Measures

  • Monocyte subsets by multiparametric flow cytometry
    • Time Frame: 24 weeks
    • change in numbers (cells/microliter of blood) of each monocyte subset (classical, intermediate, non-classical and transitional subsets)
  • Monocyte secretory function by intracellular cytokine staining release assay
    • Time Frame: 24 weeks
    • Change in percent of monocytes secreting cytokine TNFalpha, percent secreting cytokine IL-6 and percent secreting cytokine IL-1beta
  • Sub-types of coronary plaques by CT angiography
    • Time Frame: 24 weeks
    • Change in numbers of non-calcified atherosclerotic plaques detected in the coronary arteries; change in numbers of mixed plaques; change in numbers of calcified coronary plaques

Participating in This Clinical Trial

Inclusion Criteria

  • HIV+ – on suppressive ART stable for > 1 year – Age > 45 years – Ability and willingness to provide written informed consent Exclusion Criteria:

  • Uncontrolled chronic medical condition or cancer – Acute illness within 2 weeks of entry – Diagnosis of diabetes or impaired fasting glucose – Chronic diarrhea – Known hypersensitivity or contraindication to metformin use – Hepatitis C co-infection – Serum B12 level below the reference normal range as listed by the commercial laboratory (Diagnostic Laboratory Services) – Pregnancy, or intent to become pregnant – Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry. – Current or past history of coronary artery disease or congestive heart failure – Resting heart rate > 100 beats/min – Presence of conduction abnormalities or pathologic arrhythmia on EKG – The following lab values: Hemoglobin < 9.0 g/dL; Absolute neutrophil count < 1000/μL; Platelet count < 50,000/μL; and AST (SGOT) and ALT (SGPT) > 5x ULN – Calculated creatinine clearance (Cockcroft and Gault) < 60 ml/min – Patients over 450 lbs – History of iodine allergy or X-ray contrast allergy – History of allergy to metoprolol – Active or recent past history (within past 2 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements – Patients in whom there are other reasons that the CAC/CTA procedure is contra-indicated or who are at higher risk of adverse events – Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable

Gender Eligibility: All

Minimum Age: 45 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Hawaii
  • Collaborator
    • National Institute of General Medical Sciences (NIGMS)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cecilia M Shikuma, MD, Principal Investigator, University of Hawaii
  • Overall Contact(s)
    • Nancy Hanks, RN, 808 692-1336, nhanks@hawaii.edu

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