Impact of Metformin on Immuno-virologic Parameters in HIV

NCT04500678 | Unknown Phase 2 FDA Drug

• 1 other identifier: H046
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• CD4 T cell PD1+TIGIT+

  Comparison of change over time in percentage of CD4 T cells bearing the PD1+TIGIT+ surface markers in peripheral blood mononuclear cells (PBMC) in the treatment (metformin) arm compared to the observation arm

  Entry to week 72

Secondary Outcomes (6)

• CD8 T cell PD1+TIGIT+

  Entry to week 72

• Plasma levels of indoleamine 2,3-dioxygenase (IDO)

  Entry to week 72

• Peripheral blood CD4 T cell intracellular HIV DNA

  Entry to week 72

• Peripheral blood CD4 T cell intracellular HIV RNA

  Entry to week 72

• Peripheral blood monocyte intracellular HIV DNA

  Entry to week 72

Other Outcomes (6)

• Safety and Tolerability: # of grade 2 or greater adverse events in each arm

  Entry to week 72

• Carotid intima-media thickness

  Entry to week 72

• Neuropsychological testing global Z score

  Entry to week 72

Study Arms (2)

Metformin

EXPERIMENTAL

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

Drug: Metformin

Observation

NO INTERVENTION

Observed without metformin

Interventions

Metformin DRUG

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

Metformin

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Hawaii: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

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

Honolulu, Hawaii, 96813, United States

RECRUITING

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Cecilia M Shikuma, MD

  University of Hawaii

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cecilia M Shikuma, MD

CONTACT

808 692-1328; shikuma@hawaii.edu

Debra Ogata-Arakaki, RN

CONTACT

808 692-1332; ogataara@hawaii.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine

Model Details: Metformin vs Observation

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 5, 2020
• Study Start: February 1, 2019
• Primary Completion: February 1, 2022
• Study Completion: December 31, 2022
• Last Updated: August 5, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After the study analyses are completed and primary manuscript is published, and for a duration of at least 5 years afterwards
• Access Criteria: De-identified dataset will be provided upon request to legitimate researchers

Locations

US (1)