Metformin for HIV Inflammation

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

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; HIV
• Intervention / Treatment: Drug: metformin extended release

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nancy Hanks, RN; Phone Number: 808 692-1336; Email: nhanks@hawaii.edu
• Study Contact Backup: Name: Debra Ogata-Arakaki, RN; Phone Number: 808 692-1332; Email: ogataara@hawaii.edu

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Recruiting
      • Hawaii Center for AIDS
      • Contact: Debra Ogata-Arakaki, RN; Phone Number: 808 692-1332; Email: ogataara@hawaii.edu
      • Contact: Cecilia Shikuma, MD; Phone Number: 808-692-1328; Email: shikuma@hawaii.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Cecilia M Shikuma, MD, University of Hawaii

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: March 3, 2015
• First Posted (Estimate): March 9, 2015

Study Record Updates

• Last Update Posted (Estimate): March 9, 2015
• Last Update Submitted That Met QC Criteria: March 3, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: H028; P30GM103341 (U.S. NIH Grant/Contract)