Metformin for HIV Inflammation

Phase 2

• Conditions: HIV; Coronary Artery Disease
• Interventions: Drug: metformin extended release

• Registration Number: NCT02383563
• Lead Sponsor: University of Hawaii

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-09
• Status Verified: 2015-03
• Study First Submitted QC: 2015-03-03
• Last Update Submitted: 2015-03-03
• Study First Posted: 2015-03-09
• Last Update Posted: 2015-03-09
• Primary Completion: 2016-02
• Study Completion: 2016-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin Treatment Arm	metformin extended release	500 mg metformin Extended Release tablets - one tablet daily increased at 4 weeks to 2 tablets (1000 mg) daily.

Primary Outcome Measures

Name	Time	Method
Coronary plaques by CT angiography	24 weeks	change in total numbers of atherosclerotic plaques detected in the coronary arteries

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hawaii Center for AIDS; 🇺🇸 Honolulu, Hawaii, United States