Clinical trial NCT03270709: Effect of High-Dose Vitamin D3 in Smokers and Non-Smokers With and Without HIV
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: HIV/AIDS
Vitamin D Deficiency
Smoker Lung
Keywords: Vitamin D3
Pulmonary disease
Immunosuppression
HIV
Smoking
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2017-09-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A total of 44 subjects (11 per group, smokers and non-smokers, HIV+, HIV-) will be enrolled.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Difference in alveolar macrophage (AM) phagocytic index between HIV+ smokers compared to HIV- non-smokers.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in alveolar macrophage (AM) phagocytic index before and after vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
Secondary outcomes:
measure: Difference in total and free vitamin D (25(OH) D) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in peptide LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in tumor necrosis factor alpha (TNF-α) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in messenger ribonucleic acid (mRNA) expression of LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration.
measure: Difference in total and free vitamin D (25(OH) D) before and after vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
measure: Difference in peptide LL-37 before and after vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
measure: Difference in tumor necrosis factor alpha (TNF-α) before and after vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
measure: Difference in mRNA expression of LL-37 before and after vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
measure: Difference in alveolar oxidative stress before and after vitamin D administration.
timeFrame: Day 1 of the study prior to vitamin D administration, Day 7 after vitamin D administration
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Atlanta VA Medical center
state: Georgia
city: Atlanta
country: United States
facility: Grady Health System (non-CRN), Grady Health System (CRN), Ponce Center
state: Georgia
Study officials:
affiliation: Emory University
name: Jenny E Han, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: