Zinc Effect on Inflammation and Cardiovascular Risk in HIV

To study the effect of short-term zinc supplementation on improving inflammation, metabolic, and cardiovascular risk among HIV infected patients on stable anti-retroviral therapy

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Inflammation; Zinc Deficiency
• Intervention / Treatment: Drug: Zinc Gluconate; Drug: Placebo

Detailed Description

This study will focus on subjects with documented zinc deficiency (levels <75 µg/dl) as group most likely to benefit from the zinc supplementation. The investigators also acknowledge that zinc may be beneficial in all HIV subjects, regardless of the plasma zinc level; however initial studies should be done in subjects with low zinc levels as they are more likely to benefit.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV-1 infection
• Documentation of an HIV-1 RNA level of ≤400 copies/mL in the last 4 months prior to study entry
• Male or Female age ≥18 years
• Zinc level ≤0.75 mg/L in the last 60 days

Exclusion Criteria:

• Pregnancy/lactation
• Known cardiovascular disease
• Uncontrolled diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zinc gluconate; Patients received Zinc gluconate 45 mg capsules orally twice daily for 24 weeks.	Drug: Zinc Gluconate; Two 45 mg capsules once daily
Placebo Comparator: Placebo; Patients received Zinc gluconate Placebo capsules orally twice daily for 24 weeks.	Drug: Placebo; Two placebo capsules once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Zinc Supplementation on Zinc Levels at 24 Weeks in HIV-infected Subjects	Changes in zinc levels after zinc supplementation in HIV-infected subjects with zinc deficiency	between baseline and 24 weeks
Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects	Changes in markers of inflammation and immune activation by measuring monocyte activation soluble markers CD14 (sCD14), and soluble CD163 (sCD163), high sensitivity C reactive protein (hsCRP), D-dimer, vascular cell adhesion molecule-1 (VCAM), and intercellular adhesion molecule-1 (I-CAM)	between baseline and 24 Weeks
Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects	Changes in markers of inflammation and immune activation by measuring soluble tumor necrosis alpha receptor I and II (sTNFR-I and II), Interleukin-6 (IL-6), and interferon-gamma-inducible protein of 10 kDa (IP-10).	between baseline and 24 Weeks
Effect of Zinc on oxLDL in HIV-infected Subjects	Changes in oxidized low density lipoprotein (OxLDL) (U/L) over 24 weeks	between baseline and 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects	Changes in metabolic markers after zinc supplementation by measuring Non-HDL cholesterol, high-density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), Cholesterol, Cholesterol - HDL Ratio, and Triglycerides.	between baseline and 24 Weeks
Effect of Zinc Supplementation on Cholesterol - HDL Ratio at 24 Weeks in HIV-infected Subjects	Changes in metabolic markers after zinc supplementation for 24 weeks by measuring the Cholesterol - HDL Ratio	between baseline and 24 Weeks
the Effect of Zinc Supplementation on BMI at 24 Weeks in HIV-infected Subjects	Changes in metabolic markers after zinc supplementation by measuring the body mass index (BMI) (kg/m2)	between baseline and 24 Weeks
Effect of Zinc on the Waist-umbilicus at 24 Weeks in HIV-infected Subjects	Changes in metabolic markers after zinc supplementation by measuring Waist-umbilicus (cm)	between baseline and 24 Weeks
Effect of Zinc Supplementation on Weight at 24 Weeks in HIV-infected Subjects	Changes in metabolic markers after zinc supplementation by measuring body weight (lbs)	between baseline and 24 Weeks
Effect of Zinc Supplementation on Blood Pressure at 24 Weeks in HIV-	Changes in metabolic markers after zinc supplementation by measuring Systolic Blood Pressure and Diastolic Blood Pressure (mmHg)	between baseline and 24 Weeks
Effect of Zinc Supplementation on 10 Year Atherosclerotic Cardiovascular Disease at 24 Weeks in HIV-infected Subjects	Changes in metabolic markers after zinc supplementation were measured by measuring 10-year atherosclerotic cardiovascular disease (ASCVD), which is the probability (%) that an individual will have a first major ASCVD event (like a heart attack or stroke) within the next 10 years with higher scores indicating worse outcome	between baseline and 24 Weeks
Effect of Zinc Supplementation on Endothelial Function in HIV-infected Subjects	Changes in markers of endothelial function including the Reactive Hyperemic Index and Augmentation Index Endothelial function was assessed noninvasively using RH-PAT (EndoPAT 2000) with finger probes and brachial occlusion-induced hyperemia. A Reactive Hyperemia Index (RHI) was calculated from the change in pulse wave amplitude (PWA) relative to baseline in the occluded arm, corrected for corresponding changes in the contralateral, non-occluded arm to minimize the influence of non-endothelial-dependent systemic effects. An RHI value greater than 1.67 is considered normal, while a value of 1.67 or lower is considered abnormal. Higher values indicate better endothelial function.	between baseline and 24 Weeks
Effect of Zinc Supplementation on IFAB and BDG in HIV-infected Subjects	Changes in markers of Gut Integrity Markers including: intestinal fatty acid-binding protein (IFAB) and (1,3)-β-d-glucan (BDG)	between baseline and 24 Weeks
Effect of Zinc Supplementation on LBP and Zonuline in HIV-infected Subjects	Changes in markers of Gut Integrity Markers including: lipopolysaccharide-binding protein (LBP) and Zonulin.	between baseline and 24 Weeks

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: National Center for Complementary and Integrative Health (NCCIH); Case Western Reserve University
• Investigators: Principal Investigator: Grace A McComsey, MD, FIDSA, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Actual): August 2, 2024
• Study Completion (Actual): August 2, 2024

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: inflammation; Zinc; Cardiovascular Diseases risk
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Inflammation
• Other Study ID Numbers: Zinc study; 1R21AT009153 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes