Genistein for the Reduction of Adverse Cardiovascular Events (GRACE)

NCT07785388 | Not Yet Recruiting Phase 1

• 1 other identifier: 129154
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

People living with HIV (PLHIV) live longer because of modern HIV medicines, but even with these treatments, their bodies are more inflamed. Long term inflammation increases the risk of heart disease, chronic pain, lung disease, dementia, arthritis, and other infections. Because some anti-inflammatory medicines can cause serious side effects, interact with HIV drugs, or be costly, safer and more affordable treatment options are needed. Genistein is a natural compound found in soy foods. It is considered safe and has been shown to reduce inflammation and improve blood vessel health. This study will test whether genistein can lower inflammation in the blood, improve blood vessel health, and reduce pain in PLHIV.

Conditions

HIV; Vascular Disease; Inflammation; Pain Management

Keywords

HIV; Cardiovascular disease; Inflammation

Outcome Measures

Primary Outcomes (2)

• Investigate whether genistein attenuates HIV-induced inflammation.

  Blood and urine will be collected at weeks 1 (visit 1, baseline), 4 (visit 2), 8 (visit 3), 12 (visit 4) . The blood samples will be analyzed for inflammatory cytokines and proteins using Olink, SEER and/or NULISA proteomics. Plasma may be sent to Greenstone Biosciences for analysis. Urine will be tested for cannabinoids (THC) and nicotine/cotinine to confirm cannabis and tobacco use, respectively at the UH-LHSCRI Lab.

  weeks 1, 4, 8, 12 and 18.

• Investigate whether genistein attenuates HIV-induced vascular dysfunction.

  An evaluation of vascular function at weeks 1 (visit 1, baseline), 12 (visit 4) will be assessed by either endothelial peripheral arterial tonometry (EndoPAT) or flow-mediated dilation (FMD) to determine if genistein treatment improves vasodilation and constriction or vascular tone.

  at weeks 1 (visit 1, baseline) and week 12 (visit 4)

Secondary Outcomes (2)

• Investigate whether genistein reduces pain levels in PLHIV.

  at weeks 1 (visit 1, baseline), 4 (visit 2), 8 (visit 3), 12 (visit 4)

• Investigate whether genistein in PLHIV alters the gut microbiome to reduce levels of inflammation.

  at weeks 1 (visit 1, baseline), 4 (visit 2), 8 (visit 3), 12 (visit 4)

Other Outcomes (1)

• Exploratory Objective: Induced pluripotent stem cells (iPSC) reprogramming and genetic testing (optional):

  at baseline (visit 1)

Study Arms (2)

Experimental Group:

EXPERIMENTAL

HIV positive experimental group (n=30 participants) will be treated with genistein

Dietary Supplement: Genistein (Unconjugated Isoflavones 100)

Control Group

PLACEBO COMPARATOR

HIV positive experimental group (n=30 participants) will be treated with placebo

Drug: Placebo

Interventions

Genistein (Unconjugated Isoflavones 100) DIETARY_SUPPLEMENT

Genistein: 500 mg twice a day (1000 mg total) for 12 weeks, followed by a washout for 6 weeks

Experimental Group:

Placebo DRUG

Placebo: twice a day (1000 mg total) for 12 weeks, followed by a washout for 6 weeks

Control Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age: 19-80
• males and females
• all ethnicities
• no history of cardiovascular disease
• HIV positive participants (30 volunteers, experimental group)
• HIV positive participants (30 volunteers, control group)

You may not qualify if:

• if HIV positive: detectable viral load or CD4\<350
• use cannabis containing only cannabidiol (CBD)
• ingest oral tetrahydrocannabinol (THC)
• unable to provide a receipt for the cannabis product(s)they ingest
• consume soy products, genistein, isoflavonoids, and/or resveratrol
• pregnant
• breastfeeding
• endometriosis
• uterine fibroids
• have cancer (breast cancer, predisposition to cancer such as abnormal mammogram, family history, BRCA1/BRCA2 positive)
• liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\>3X ULN, total bilirubin greater than 1.5 times ULN)
• hormone replacement therapy (HRT)
• thyroid supplements
• renal dysfunction (eGFR less than 25 mL/min/1.73 m2)
• uncontrolled diabetes (HgbA1c\>10%)

Sponsors & Collaborators

• Greenstone Biosciences, Inc.: collaborator
• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Regional Health Science Centre

London, Ontario, N6A 5A5, Canada

Location

MeSH Terms

Conditions

Vascular Diseases; Inflammation; Agnosia; Cardiovascular Diseases

Interventions

Genistein

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mark JK Chandy, MD PhD

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark JK Chandy, MD PhD

CONTACT

519-661-2111; mark.chandy@lhsc.on.ca

Kerry-Ann Laboratory Manager, PhD

CONTACT

519-661-2111; Kerry-Ann.Nakrieko@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The systemic inflammation in PLHIV is well established as well as the limitations of therapies, notably the undesirable side effects of current anti-inflammatory medications. This study aims to investigate the efficacy of genistein in countering the systemic inflammation underlying CVD risk and chronic pain in PLHIV, including those whose vascular dysfunction may be exacerbated by cannabis use. The primary objectives are to evaluate genistein's impact on inflammatory and cardiometabolic biomarkers, as well as vascular function and pain level. This study also incorporates two exploratory objectives: an investigation on whether the microbiome is a key modulator of inflammatory markers and the use of induced pluripotent stem cells (iPSCs) derived from participant blood samples to assess cellular mechanisms influenced by genistein. This complementary approach will provide mechanistic insight into genistein's therapeutic potential in PLHIV.

Study Record Dates

• First Submitted: August 21, 2026
• First Posted: August 25, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: August 25, 2026

Record last verified: 2026-08

Locations

CA (1)