Metformin for HIV Inflammation

Study Overview
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Brief Summary
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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.

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

Conditions
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HIV, Coronary Artery Disease

Intervention / Treatment
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* Drug: metformin extended release


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin Treatment Arm<br>500 mg metformin Extended Release tablets - one tablet daily increased at 4 weeks to 2 tablets (1000 mg) daily. | Drug: metformin extended release<br> <br> |
| No Intervention: Observational Arm<br>Observation only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary plaques by CT angiography | change in total numbers of atherosclerotic plaques detected in the coronary arteries | 24 weeks | 

Secondary Outcome Measures

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