Effect of High-Dose Vitamin D3 in Smokers and Non-Smokers With and Without HIV

• ClinicalTrials.gov Identifier: NCT03270709
• Recruitment Status: Terminated
• First Posted: September 1, 2017
• Last Update Posted: April 21, 2021
• Sponsor: Emory University
• Information provided by (Responsible Party): Jenny Elizabeth Han, Emory University

Study Description

Brief Summary:

Supplementation with vitamin D improves HIV+ macrophages phagocytosis in vitro. There is evidence to suggest that administering vitamin D can in fact improve immune function in individuals. The study will evaluate the impact of high dose vitamin D in HIV+ smokers' and HIV- smokers' in vivo. The primary goal is to improve innate immune host response to infection in patients already at high risk by virtue of HIV and smoking status.

Condition or disease	Intervention/treatment	Phase
HIV/AIDS; Vitamin D Deficiency; Smoker Lung	Drug: Vitamin D3 450,000 IU orally	Phase 1

Detailed Description:

Tobacco smoke suppresses the lung's ability to fight infection. Smoking is three times more prevalent in the HIV+ compared to HIV- patients. Viral load was found to be significantly increased in HIV+ smokers compared to HIV+ non-smokers, suggesting that smoking enhances HIV-1 viral replication in macrophages, which contributes to disease progression. Vitamin D deficiency has been associated with increased mortality in HIV+ persons, but there is limited research on how this is impacting the health of these highest risk patients and if aggressive repletion with vitamin D can improve overall health.The study team hypothesizes that vitamin D administration will increase pathogen clearance and improve innate immune function.

The proposed pre and post interventional study is designed to characterize alveolar macrophage function and lung immunity according to tobacco use and HIV status, and determine the impact of high dose oral vitamin D3 on AM phagocytic function and innate immunity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A total of 44 subjects (11 per group, smokers and non-smokers, HIV+, HIV-) will be enrolled.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of High-Dose Vitamin D3 on Alveolar Macrophage Function, LL-37, and Oxidative Stress in Smokers and Non-Smokers With and Without HIV
• Actual Study Start Date: April 11, 2018
• Actual Primary Completion Date: October 15, 2018
• Actual Study Completion Date: October 15, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: HIV+ smokers; Vitamin D3 450,000 IU orally	Drug: Vitamin D3 450,000 IU orally; Study subjects will receive 2 tablets of vitamin D3 for a total of 450,000 IU by mouth.
Active Comparator: HIV- non-smokers; Vitamin D3 450,000 IU orally	Drug: Vitamin D3 450,000 IU orally; Study subjects will receive 2 tablets of vitamin D3 for a total of 450,000 IU by mouth.
Active Comparator: HIV+ non-smokers; Vitamin D3 450,000 IU orally	Drug: Vitamin D3 450,000 IU orally; Study subjects will receive 2 tablets of vitamin D3 for a total of 450,000 IU by mouth.
Active Comparator: HIV- smokers; Vitamin D3 450,000 IU orally	Drug: Vitamin D3 450,000 IU orally; Study subjects will receive 2 tablets of vitamin D3 for a total of 450,000 IU by mouth.

Outcome Measures

Primary Outcome Measures :

1. Difference in alveolar macrophage (AM) phagocytic index between HIV+ smokers compared to HIV- non-smokers. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.
2. Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers will be calculated.
3. Difference in alveolar macrophage (AM) phagocytic index before and after vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration ]
   A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.

Secondary Outcome Measures :

1. Difference in total and free vitamin D (25(OH) D) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   Difference in total and free 25(OH) D between HIV+ smokers compared to HIV- non-smokers will be measure by ELISA (enzyme-linked immunosorbent assay) levels.
2. Difference in peptide LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   Difference in an antimicrobial and immunostimulating/-modulating peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.
3. Difference in tumor necrosis factor alpha (TNF-α) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   Difference in tumor necrosis factor alpha (TNF-α) - cytokine involved in systemic inflammation - between HIV+ smokers compared to HIV- non-smokers will be calculated .
4. Difference in messenger ribonucleic acid (mRNA) expression of LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   Difference in mRNA expression of antimicrobial peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.
5. Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration. ]
   Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers will be measured using AM isolated from bronchoalveolar lavage (BAL) .
6. Difference in total and free vitamin D (25(OH) D) before and after vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration ]
   Difference in total and free vitamin D (25(OH) D) will be measure by ELISA (enzyme-linked immunosorbent assay)
7. Difference in peptide LL-37 before and after vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration ]
   Difference in peptide LL-37 levels will be calculated.
8. Difference in tumor necrosis factor alpha (TNF-α) before and after vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration ]
   Difference in tumor necrosis factor alpha (TNF-α) will be calculated.
9. Difference in mRNA expression of LL-37 before and after vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration ]
   Difference in mRNA expression of LL-37 will be calculated.
10. Difference in alveolar oxidative stress before and after vitamin D administration. [ Time Frame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration ]
    Difference in alveolar oxidative stress will be measured using AM isolated from bronchoalveolar lavage (BAL) .

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Subjects living with HIV-1 infection who have been on anti-retroviral therapy (ART) for a minimum of 12 months and are followed longitudinally for their HIV healthcare;
• Ability to give informed consent.

Exclusion Criteria:

• Age <18 yrs old;
• Known or possible pregnancy or breastfeeding;
• Documented history of cirrhosis or a direct bilirubin ≥ 2.0 mg/dL;
• Documentation of left ventricular ejection fraction < 40% or myocardial infarction within the past 6 months;
• End-stage renal disease requiring dialysis or a serum creatinine ≥ 2 mg/d;
• Spirometry with forced vital capacity (FVC) or forced expiratory volume (FEV1)< 70% of predicted value;
• Bleeding disorders such as thrombocytopenia or significant gastrointestinal bleeding within the past year;
• Inability to undergo bronchoscopy safely;
• High risk behaviors without known HIV status.

Contacts and Locations

Locations

United States, Georgia

Atlanta VA Medical center

Atlanta, Georgia, United States, 30303

Grady Health System (non-CRN), Grady Health System (CRN), Ponce Center

Atlanta, Georgia, United States, 30303

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: Jenny E Han, MD, MSc; Emory University

More Information

• Responsible Party: Jenny Elizabeth Han, Assistant Professor, Emory University
• ClinicalTrials.gov Identifier: NCT03270709
• Other Study ID Numbers: IRB00094833
• First Posted: September 1, 2017
• Last Update Posted: April 21, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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.: No

Keywords provided by Jenny Elizabeth Han, Emory University:

Vitamin D3; Pulmonary disease; Immunosuppression; HIV; Smoking

Additional relevant MeSH terms:

Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Vitamin D; Cholecalciferol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents