Impact of Metformin on Immuno-virologic Parameters in HIV

NCT ID: NCT04500678

Last Updated: 2020-08-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-01
• Study Completion Date: 2022-12-31

Brief Summary

Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). As secondary objectives the study will look at 72 week change in other immuno-virologic parameters (CD8 T cell negative checkpoint receptors, plasma indoleamine 2,3-dioxygenase (IDO) levels and CD4 T cell and monocyte intracellular HIV DNA and HIV RNA. The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.

Conditions

HIV/AIDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

Metformin

Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.

Observation

Observed without metformin

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metformin

Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HIV+
• On suppressive ART stable for > 1 year
• Plasma HIV RNA < 50 copies/mL within 3 months of entry, with no HIV RNA > 200 copies/mL within the past 6 months prior to entry
• Age >40 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 by history, fasting blood glucose >126, or by HgbA1c > 6.5
• Chronic, uncontrolled diarrhea
• Known hypersensitivity or contraindication to metformin use
• Current presence of hepatitis C including currently on or intent to start therapy for hepatitis C within the 48 week duration of study.
• Serum B12 level below the reference normal range as listed by the commercial lab utilized for this study (Diagnostic Laboratory Services)
• Pregnancy, or intent to become pregnant or nursing an infant
• Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
• Current uncontrolled coronary artery disease or NYHA Class 3 or 4 congestive heart failure
• History of liver cirrhosis
• Current use of zidovudine, stavudine or didanosine
• The following lab values

• Hemoglobin < 9.0 g/dL
• Absolute neutrophil count < 1000/μL
• Platelet count < 50,000/μL
• AST (SGOT) and ALT (SGPT) > 5x upper limit of normal (ULN)
• Calculated creatinine clearance (Cockcroft and Gault) < 50 ml/min
• 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, 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Hawaii

OTHER

Sponsor Role: lead

Responsible Party

Cecilia Shikuma

Professor, Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cecilia M Shikuma, MD

Role: PRINCIPAL_INVESTIGATOR

University of Hawaii

Locations

John A. Burns School of Medicine, University of Hawaii - Manoa

Honolulu, Hawaii, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Cecilia M Shikuma, MD

Role: CONTACT

shikuma@hawaii.edu

808 692-1328

Debra Ogata-Arakaki, RN

Role: CONTACT

ogataara@hawaii.edu

808 692-1332

Facility Contacts

Cecilia Shikuma, MD

Role: primary

shikuma@hawaii.edu

808-692-1328

Debra Ogata-Arakaki, RN

Role: backup

ogataara@hawaii.edu

808 692-1332

Other Identifiers

H046

Identifier Type: -

Identifier Source: org_study_id