Inflammation, Cardiovascular Diseases, Zinc Deficiency
Conditions
Keywords
Zinc, inflammation, Cardiovascular Diseases risk
Brief summary
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
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.
Interventions
DRUGZinc Gluconate
Two 45 mg capsules once daily
DRUGPlacebo
Two placebo capsules once daily
Sponsors
Case Western Reserve University
National Center for Complementary and Integrative Health (NCCIH)
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients, study staff, and the study statistician will be blinded to treatment allocation (zinc gluconate or placebo capsules). The research staff as well as the principle investigator will remain blinded to treatment assignment.
Intervention model description
This is a double-blind randomized placebo-controlled trial 2:1 Patients will be given zinc gluconate capsules at a dose of 90 mg elemental zinc daily or matching placebo for 24 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Zinc Supplementation on Zinc Levels at 24 Weeks in HIV-infected Subjects | between baseline and 24 weeks | Changes in zinc levels after zinc supplementation in HIV-infected subjects with zinc deficiency |
| Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | between baseline and 24 Weeks | 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) |
| Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | between baseline and 24 Weeks | 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). |
| Effect of Zinc on oxLDL in HIV-infected Subjects | between baseline and 24 Weeks | Changes in oxidized low density lipoprotein (OxLDL) (U/L) over 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Zinc Supplementation on Weight at 24 Weeks in HIV-infected Subjects | between baseline and 24 Weeks | Changes in metabolic markers after zinc supplementation by measuring body weight (lbs) |
| Effect of Zinc Supplementation on Blood Pressure at 24 Weeks in HIV- | between baseline and 24 Weeks | Changes in metabolic markers after zinc supplementation by measuring Systolic Blood Pressure and Diastolic Blood Pressure (mmHg) |
| Effect of Zinc Supplementation on 10 Year Atherosclerotic Cardiovascular Disease at 24 Weeks in HIV-infected Subjects | between baseline and 24 Weeks | 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 |
| Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | between baseline and 24 Weeks | 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. |
| Effect of Zinc Supplementation on IFAB and BDG in HIV-infected Subjects | between baseline and 24 Weeks | Changes in markers of Gut Integrity Markers including: intestinal fatty acid-binding protein (IFAB) and (1,3)-β-d-glucan (BDG) |
| Effect of Zinc Supplementation on LBP and Zonuline in HIV-infected Subjects | between baseline and 24 Weeks | Changes in markers of Gut Integrity Markers including: lipopolysaccharide-binding protein (LBP) and Zonulin. |
| Effect of Zinc Supplementation on Endothelial Function in HIV-infected Subjects | between baseline and 24 Weeks | 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. |
| Effect of Zinc Supplementation on Cholesterol - HDL Ratio at 24 Weeks in HIV-infected Subjects | between baseline and 24 Weeks | Changes in metabolic markers after zinc supplementation for 24 weeks by measuring the Cholesterol - HDL Ratio |
| the Effect of Zinc Supplementation on BMI at 24 Weeks in HIV-infected Subjects | between baseline and 24 Weeks | Changes in metabolic markers after zinc supplementation by measuring the body mass index (BMI) (kg/m2) |
| Effect of Zinc on the Waist-umbilicus at 24 Weeks in HIV-infected Subjects | between baseline and 24 Weeks | Changes in metabolic markers after zinc supplementation by measuring Waist-umbilicus (cm) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zinc Gluconate Patients received Zinc gluconate 45 mg capsules orally twice daily for 24 weeks.
Zinc Gluconate: Two 45 mg capsules once daily | 63 |
| Placebo Patients received Zinc gluconate Placebo capsules orally twice daily for 24 weeks.
Placebo: Two placebo capsules once daily | 32 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Inability to swallow the pill | 0 | 1 |
| Overall Study | Lost to Follow-up | 9 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | Zinc Gluconate |
|---|---|---|---|
| Age, Continuous | 52.42 years | 53.29 years | 52.42 years |
| alcohol (current) | 66 Participants | 21 Participants | 45 Participants |
| Anti-Retroviral Treatment Duration | 171.86 Months | 167.86 Months | 178.76 Months |
| atherosclerotic cardiovascular risk 10 year ASCVD | 6.5 % | 6.7 % | 6.1 % |
| BDG | 106.08 pg/mL | 122.51 pg/mL | 98.46 pg/mL |
| Body Mass Index BMI | 28.08 kg/m2 | 27.45 kg/m2 | 28.34 kg/m2 |
| CD4+ T-Cell Count | 722.00 cells/mm³ | 668.00 cells/mm³ | 747.00 cells/mm³ |
| Cholesterol | 169 mg/dl | 165.5 mg/dl | 171 mg/dl |
| cholesterol/ high Density Lipoprotein Ratio | 3.4 Ratio | 3.2 Ratio | 3.5 Ratio |
| DDimer | 536.22 ng/mL | 520.93 ng/mL | 558.43 ng/mL |
| Diastolic Blood Pressure | 81 mmHg | 82 mmHg | 80 mmHg |
| Endothelial Function: Augmentation Index | 10 % | 11 % | 7.5 % |
| Endothelial Function: Reactive Hyperemic Index | 1.9 ratio | 1.89 ratio | 1.91 ratio |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 27 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| High Density Lipoprotein | 47.00 mg/dL | 48.15 mg/dL | 45.40 mg/dL |
| HIV RNA (<20 copies) | 74 Participants | 23 Participants | 51 Participants |
| hsCRP | 2202.14 ng/mL | 1998.85 ng/mL | 2240.00 ng/mL |
| ICAM | 247.37 ng/mL | 250.13 ng/mL | 244.28 ng/mL |
| IFAB | 1730.93 pg/mL | 1616.94 pg/mL | 1826.49 pg/mL |
| IL-6 | 1.94 pg/mL | 1.89 pg/mL | 2.11 pg/mL |
| Insulin | 10.5 mIU/mL | 11.5 mIU/mL | 10 mIU/mL |
| IP-10 | 134.48 pg/mL | 134.70 pg/mL | 130.52 pg/mL |
| LBP | 16.6 μg/mL | 16.44 μg/mL | 16.6 μg/mL |
| Low Density Lipoprotein LDL | 96 mg/dl | 89 mg/dl | 96 mg/dl |
| Non-High Density Lipoprotein non-HDL cholesterol | 115.30 (mg/dL | 115.50 (mg/dL | 115.30 (mg/dL |
| oxLDL | 50145.48 U/L | 47606.57 U/L | 51731.12 U/L |
| Presence of metabolic syndrome | 40 Participants | 14 Participants | 26 Participants |
| Protease Inhibitor use | 15 Participants | 7 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 56 Participants | 18 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 37 Participants | 14 Participants | 23 Participants |
| sCD14 | 1681.63 ng/mL | 1727.05 ng/mL | 1671.20 ng/mL |
| sCD163 | 568.55 ng/mL | 593.61 ng/mL | 543.40 ng/mL |
| Sex: Female, Male Female | 25 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 70 Participants | 26 Participants | 44 Participants |
| smokers (current) | 29 Participants | 13 Participants | 16 Participants |
| sTNFR-I | 1006.42 pg/mL | 977.39 pg/mL | 1036.85 pg/mL |
| sTNFR-II | 2234.54 pg/mL | 2253.23 pg/mL | 2162.27 pg/mL |
| Systolic Blood Pressure | 126 mmHg | 129 mmHg | 125 mmHg |
| Triglycerides | 105 mg/dl | 103 mg/dl | 108 mg/dl |
| VCAM | 783.99 ng/mL | 857.01 ng/mL | 758.04 ng/mL |
| Very Low Density Lipoprotein VLDL | 21 mg/dl | 20 mg/dl | 22 mg/dl |
| Waist circumference | 97.00 cm | 97.83 cm | 96.67 cm |
| Zinc level | 69.8 μg/dL | 69 μg/dL | 70 μg/dL |
| Zonulin | 1030 μg/mL | 1040 μg/mL | 1020 μg/mL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 63 | 0 / 32 |
| other Total, other adverse events | 48 / 63 | 27 / 32 |
| serious Total, serious adverse events | 1 / 63 | 0 / 32 |
Outcome results
Primary
Effect of Zinc on oxLDL in HIV-infected Subjects
Changes in oxidized low density lipoprotein (OxLDL) (U/L) over 24 weeks
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Effect of Zinc on oxLDL in HIV-infected Subjects | 20833.33 U/L |
| Zinc 90 mg | Effect of Zinc on oxLDL in HIV-infected Subjects | 8639.79 U/L |
Comparison: effect of Zinc supplementation on ln(OxLDL, U/L)p-value: 0.8395% CI: [-14899.37, 18537.74]linear combination of coefficients
Primary
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)
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | hsCRP (ng/mL) | -22.86 ng/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | sCD163 (ng/mL) | -50.11 ng/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | VCAM (ng/mL) | 66.69 ng/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | D-dimer (ng/mL) | -149.05 ng/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | ICAM (ng/mL) | -2.03 ng/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | sCD14 (ng/mL) | 101.71 ng/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | ICAM (ng/mL) | 2.35 ng/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | VCAM (ng/mL) | 49.53 ng/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | hsCRP (ng/mL) | 1.33 ng/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | sCD14 (ng/mL) | -56.31 ng/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | sCD163 (ng/mL) | 43.69 ng/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation and Immune Activation in HIV-infected Subjects | D-dimer (ng/mL) | -45.85 ng/mL |
Comparison: effect of Zinc supplementation on ln(hsCRP ng/mL)p-value: 195% CI: [-0.57, 0.57]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(sCD14, ng/mL)p-value: 0.0895% CI: [-0.18, 0.01]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(sCD163, ng/mL)p-value: 0.7795% CI: [-0.21, 0.15]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(D-dimer, ng/mL)p-value: 0.1995% CI: [-0.1, 0.5]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(VCAM, ng/mL)p-value: 0.195% CI: [-0.41, 0.04]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(ICAM, ng/mL)p-value: 0.9895% CI: [-39.16, 39.98]linear combination of coefficients
Primary
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).
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | sTNF-RI (pg/mL) | -25.08 pg/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | sTNF-RII (pg/mL) | -121.65 pg/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | IP-10 (pg/mL) | 0.23 pg/mL |
| Placebo | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | IL-6 (pg/mL) | -0.47 pg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | IL-6 (pg/mL) | -0.02 pg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | sTNF-RI (pg/mL) | 1.27 pg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | IP-10 (pg/mL) | -9.99 pg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on Inflammation in HIV-infected Subjects | sTNF-RII (pg/mL) | 99.33 pg/mL |
Comparison: effect of Zinc supplementation on ln(sTNF-RI , pg/mL)p-value: 0.5595% CI: [-0.09, 0.16]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(sTNF-RII, pg/m)p-value: 0.9595% CI: [-0.13, 0.13]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(IL-6, pg/mL)p-value: 0.7395% CI: [-0.3, 0.43]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(IP-10, pg/mL)p-value: 0.4895% CI: [-0.22, 0.47]linear combination of coefficients
Primary
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
Time frame: between baseline and 24 weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Effect of Zinc Supplementation on Zinc Levels at 24 Weeks in HIV-infected Subjects | 8.60 absolute change (μg/dL) |
| Zinc 90 mg | Effect of Zinc Supplementation on Zinc Levels at 24 Weeks in HIV-infected Subjects | 33.50 absolute change (μg/dL) |
Comparison: effect of Zinc supplementation on ln(Zinc, μg/dL)p-value: <0.0195% CI: [0.43, 0.98]linear combination of coefficients
Secondary
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)
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Effect of Zinc on the Waist-umbilicus at 24 Weeks in HIV-infected Subjects | 0.50 cm |
| Zinc 90 mg | Effect of Zinc on the Waist-umbilicus at 24 Weeks in HIV-infected Subjects | 1.67 cm |
Comparison: effect of Zinc supplementation on ln(Waist-umbilicus (cm))p-value: 0.7495% CI: [-0.08, 0.05]linear combination of coefficients
Secondary
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
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Effect of Zinc Supplementation on 10 Year Atherosclerotic Cardiovascular Disease at 24 Weeks in HIV-infected Subjects | 0.40 percentage of 10-year ASCVD score |
| Zinc 90 mg | Effect of Zinc Supplementation on 10 Year Atherosclerotic Cardiovascular Disease at 24 Weeks in HIV-infected Subjects | 0.00 percentage of 10-year ASCVD score |
Comparison: effect of Zinc supplementation on ln(10 year ASCVD (%))p-value: 0.795% CI: [-0.26, 0.17]linear combination of coefficients
Secondary
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)
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on Blood Pressure at 24 Weeks in HIV- | Systolic Blood Pressure (mmHg) | 6.00 mmHg |
| Placebo | Effect of Zinc Supplementation on Blood Pressure at 24 Weeks in HIV- | Diastolic Blood Pressure (mmHg) | 3.00 mmHg |
| Zinc 90 mg | Effect of Zinc Supplementation on Blood Pressure at 24 Weeks in HIV- | Diastolic Blood Pressure (mmHg) | 0.00 mmHg |
| Zinc 90 mg | Effect of Zinc Supplementation on Blood Pressure at 24 Weeks in HIV- | Systolic Blood Pressure (mmHg) | 0.00 mmHg |
Comparison: effect of Zinc supplementation on ln(Systolic blood pressure (mmHg))p-value: 0.4195% CI: [-0.07, 0.03]linear combination of coefficients
Comparison: effect of Zinc supplementation on Diastolic blood pressure (mmHg)p-value: 0.4295% CI: [-5.71, 2.36]linear combination of coeff
Secondary
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
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Effect of Zinc Supplementation on Cholesterol - HDL Ratio at 24 Weeks in HIV-infected Subjects | 0.10 Ratio |
| Zinc 90 mg | Effect of Zinc Supplementation on Cholesterol - HDL Ratio at 24 Weeks in HIV-infected Subjects | 0.10 Ratio |
Comparison: effect of Zinc supplementation on ln(Chol:HDL Ratio)p-value: 0.3695% CI: [-0.07, 0.2]linear combination of coefficients
Secondary
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.
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on Endothelial Function in HIV-infected Subjects | Augmentation Index | 0.00 (ratio) absolute change |
| Placebo | Effect of Zinc Supplementation on Endothelial Function in HIV-infected Subjects | Reactive Hyperemic Index | -0.34 (ratio) absolute change |
| Zinc 90 mg | Effect of Zinc Supplementation on Endothelial Function in HIV-infected Subjects | Augmentation Index | -1.00 (ratio) absolute change |
| Zinc 90 mg | Effect of Zinc Supplementation on Endothelial Function in HIV-infected Subjects | Reactive Hyperemic Index | -0.18 (ratio) absolute change |
Comparison: effect of Zinc supplementation on Reactive Hyperemic Indexp-value: 0.6295% CI: [-0.17, 0.1]linear combination of coefficients
Comparison: effect of Zinc supplementation on Augmentation Indexp-value: 0.8195% CI: [-4.19, 5.36]linear combination of coefficients
Secondary
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)
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on IFAB and BDG in HIV-infected Subjects | IFAB (pg/mL) | 100.82 pg/mL |
| Placebo | Effect of Zinc Supplementation on IFAB and BDG in HIV-infected Subjects | BDG (pg/mL) | -28.19 pg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on IFAB and BDG in HIV-infected Subjects | IFAB (pg/mL) | 58.89 pg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on IFAB and BDG in HIV-infected Subjects | BDG (pg/mL) | 8.36 pg/mL |
Comparison: effect of Zinc supplementation on ln(IFAB (pg/mL))p-value: 0.995% CI: [-0.26, 0.3]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(BDG (pg/mL))p-value: 0.2495% CI: [-0.12, 0.47]linear combination of coefficients
Secondary
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.
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on LBP and Zonuline in HIV-infected Subjects | LBP (μg/mL) | 0.47 μg/mL |
| Placebo | Effect of Zinc Supplementation on LBP and Zonuline in HIV-infected Subjects | Zonulin (μg/mL) | 78.2 μg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on LBP and Zonuline in HIV-infected Subjects | LBP (μg/mL) | 0.72 μg/mL |
| Zinc 90 mg | Effect of Zinc Supplementation on LBP and Zonuline in HIV-infected Subjects | Zonulin (μg/mL) | 270.54 μg/mL |
Comparison: effect of Zinc supplementation on ln(LBP (ng/mL))p-value: 0.6995% CI: [-0.21, 0.32]v
Comparison: effect of Zinc supplementation on ln(Zonulin (ng/mL)p-value: 0.4995% CI: [-0.16, 0.34]linear combination of coefficients
Secondary
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.
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | Non-HDL cholesterol (mg/dL) | 3.10 mg/dL |
| Placebo | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | HDL (mg/dL) | -1.70 mg/dL |
| Placebo | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | VLDL (mg/dL) | 0.50 mg/dL |
| Placebo | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | LDL (mg/dL) | 6.00 mg/dL |
| Placebo | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | Cholesterol (mg/dL) | 2.00 mg/dL |
| Placebo | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | Triglycerides (mg/dL) | 2.00 mg/dL |
| Zinc 90 mg | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | Cholesterol (mg/dL) | -3.50 mg/dL |
| Zinc 90 mg | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | Non-HDL cholesterol (mg/dL) | 1.35 mg/dL |
| Zinc 90 mg | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | VLDL (mg/dL) | 2.00 mg/dL |
| Zinc 90 mg | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | HDL (mg/dL) | -2.45 mg/dL |
| Zinc 90 mg | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | LDL (mg/dL) | -1.50 mg/dL |
| Zinc 90 mg | Effect of Zinc Supplementation on Metabolic Markers at 24 Weeks in HIV-infected Subjects | Triglycerides (mg/dL) | 7.00 mg/dL |
Comparison: effect of Zinc supplementation on ln(Non-HDL Cholesterol (mg/dL))p-value: 0.8495% CI: [-0.12, 0.15]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(HDL (mg/dL))p-value: 0.1895% CI: [-0.19, 0.04]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(LDL (mg/dL))p-value: 0.8495% CI: [-0.19, 0.15]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(VLDL (mg/dL))p-value: 0.5595% CI: [-0.15, 0.29]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(Cholesterol (mg/dl))p-value: 0.7895% CI: [-0.11, 0.09]linear combination of coefficients
Comparison: effect of Zinc supplementation on ln(Triglycerides (mg/dL))p-value: 0.5895% CI: [-0.17, 0.31]linear combination of coefficients
Comparison: effect of Zinc supplementation on Metabolic Syndromep-value: 0.3595% CI: [-1.36, 0.48]linear combination of coefficients
Secondary
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)
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Effect of Zinc Supplementation on Weight at 24 Weeks in HIV-infected Subjects | 2.20 lbs |
| Zinc 90 mg | Effect of Zinc Supplementation on Weight at 24 Weeks in HIV-infected Subjects | 0.00 lbs |
Comparison: effect of Zinc supplementation on Weight (lbs)p-value: 0.8195% CI: [-26.97, 20.99]linear combination of coefficients
Secondary
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)
Time frame: between baseline and 24 Weeks
Population: absolute changes for outcome measures over 24 weeks for each group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | the Effect of Zinc Supplementation on BMI at 24 Weeks in HIV-infected Subjects | 0.28 kg/m2 |
| Zinc 90 mg | the Effect of Zinc Supplementation on BMI at 24 Weeks in HIV-infected Subjects | 0.10 kg/m2 |
Comparison: effect of Zinc supplementation on BMI (kg/m2)p-value: 0.8695% CI: [-4.29, 3.6]linear combination of coefficients