Metformin for HIV Inflammation

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02383563
• Other study ID #: H028
• Secondary ID: P30GM103341
• Status: Recruiting
• Phase: Phase 2
• First received: February 9, 2015
• Last updated: March 3, 2015
• Start date: February 2015
• Est. completion date: February 2016

Study information

• Verified date: March 2015
• Source: University of Hawaii
• Contact: Nancy Hanks, RN
• Phone: 808 692-1336
• Email: nhanks[@]hawaii.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• HIV
• Myocardial Ischemia

Intervention

Drug:
• metformin extended release

Locations

Country	Name	City	State
United States	Hawaii Center for AIDS	Honolulu	Hawaii

Sponsors (2)

Lead Sponsor	Collaborator
University of Hawaii	National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coronary plaques by CT angiography	change in total numbers of atherosclerotic plaques detected in the coronary arteries	24 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No