A Pilot Study of Metformin to Reduce Cerebrovascular Dysfunction in Participants With HIV and Metabolic Syndrome.

NCT05571319 | Completed Phase 2 DMC

• 2 other identifiers: M21/10/024R21TW012185-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic syndrome is a constellation of risk factors for cardiovascular disease and type 2 diabetes mellitus which frequently occur together. Data is emerging suggesting metabolic syndrome causes brain disease by contributing to blood vessel damage and inflammation. People living with HIV (PLWH) are at high risk and the investigators will perform a pilot study of the well-known type 2 diabetes drug metformin to treat this blood vessel damage and inflammation in PLWH.

Conditions

Metabolic Syndrome; HIV Seropositivity

Keywords

pilot open label trial; cerebrovascular dysfunction; endothelial function

Outcome Measures

Primary Outcomes (3)

• Outcome: cerebral reactivity.

  We will measure changes in cerebrovascular reactivity (percentage change of BOLD signal during resting state fMRI) from baseline to 12 weeks.

  12 weeks

• Outcome: cerebral blood flow.

  We will measure changes in cerebral blood flow (mL/100mL/min, via arterial spin labeling) from baseline to 12 weeks.

  12 weeks

• Outcome: peripheral vascular reactivity.

  We will measure changes in finger reactive hyperemia index from baseline to 12 weeks.

  12 weeks

Study Arms (1)

Open-label arm

EXPERIMENTAL

All participants to receive metformin extended-release 1000mg to 2000mg daily for 12 weeks.

Drug: Metformin Extended Release Oral Tablet

Interventions

Metformin Extended Release Oral Tablet DRUG

Glucophage XR 500 mg

Open-label arm

Eligibility Criteria

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

You may qualify if:

• Adult (\>18 years);
• HIV+ on antiretroviral therapy for at least 12 months prior to study entry;
• Viral load ≤50 copies/mL;
• Able to provide informed consent;
• Metabolic syndrome as per the harmonized criteria;
• Women of child-bearing potential willing to use adequate contraception (defined as either an intra-uterine contraceptive device or hormonal contraceptive);

You may not qualify if:

• Treated with metformin as part of care;
• History of drug or alcohol abuse within 3 months before screening;
• Known neurosyphilis;
• Known vitamin B12 deficiency;
• Known neuropsychiatric disorders or serious psychiatric symptoms;
• Significant head trauma with imaging structural abnormalities;
• Renal impairment (estimated glomerular filtration \< 60 mL/min/1.73m2);
• Type I or type II diabetes (fasting plasma glucose \>7mmol/L and/or HbA1c \>6.5%);
• Hypersensitivity to metformin;
• Any contraindication or special precaution in the metformin package insert which may put the participant at a safety risk;
• Cationic drugs (as listed in the metformin package insert) that may increase metformin concentrations significantly;
• Claustrophobia, metal implants or any other condition that prevents performing MR scan;
• Pregnant / breastfeeding;

Sponsors & Collaborators

• University of Stellenbosch: lead
• University of Rochester: collaborator
• Fogarty International Center of the National Institute of Health: collaborator

Study Sites (1)

Desmond Tutu Health Foundation: Gugulethu Research Site

Cape Town, Western Cape, 8001, South Africa

Location

MeSH Terms

Conditions

Metabolic Syndrome; HIV Seropositivity

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Eric Decloedt, MBChB, PhD

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor & Head of Clinical Pharmacology

Model Details: We will enroll 30 participants in an open-label study of metformin treatment for 12 weeks with a 4-week washout period and a final evaluation. The 4-week washout period was chosen to assess the post-treatment effect of metformin on peripheral markers of endothelial function, with expectation that those measurements will trend toward the baseline values.

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: October 7, 2022
• Study Start: August 11, 2022
• Primary Completion: March 24, 2025
• Study Completion: March 28, 2025
• Last Updated: October 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within10 working days after all the permissions have been obtained.
• Access Criteria: Legitimate and appropriate requests (as evaluated by the investigators, sponsor, funder and ethics committee).

Locations

ZA (1)