Clinical trial NCT02585791: Evaluation of Acute and Subacute Effects of Nicotine Free Electronic Cigarette(NCFE) Vapors
Official title: EVALUATION OF ACUTE AND SUBACUTE EFFECTS OF NICOTINE FREE ELECTRONIC CIGARETTE (NFEC) VAPORS -Aim 2.1 of "Adverse Effects of Inhaled Nicotine From Tobacco and E-cigarettes".
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy Lifetime Non-smokers
Keywords: electronic cigarette
airway inflammation
nasal potential difference
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: James and Esther King Biomedical Research Program
First posted: 2015-10-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This aim will examine the acute and subacute exposures to electronic cigarette (EC) vapor generated from e-liquids without nicotine (NFEC) on life-time non smokers subjects by measuring changes in nasal ion transport and TGF-β levels. Nasal ion transport will be assessed by nasal potential difference (NPD). Tumor growth factor (TGF)-β levels (mRNA and protein by ELISA) will be assessed on nasal cells and lavages.

Detailed description: The recent introduction of electronic cigarettes (ECs) to provide habitual smokers a source of nicotine without the need to inhale tobacco smoke is thought to reduce toxicity to airway epithelial cells. The use of ECs decreases use of traditional cigarettes diminishes nicotine withdrawal symptoms leads to opposite effects on exhaled NO levels compared to tobacco and may diminish stimulation of reward centers in the brain leading to less dependence due to the lack of other tobacco-derived chemicals. The manufacturers of ECs tout comparative safety as a reason to switch from traditional tobacco cigarettes to their products. However the dearth of data supporting this claim led the FDA to issue warning letters to these companies. For now, the World Health Organization recommends against EC use until ECs have been properly evaluated. On the other hand, the American Association of Public Health Physicians support the use of ECs as a means of "Harms Reduction" since ECs provide nicotine without the myriad of other toxic chemicals produced from burning tobacco. These recommendations are mostly due to theoretical considerations and expert opinion. Due to the novelty of the ECs, many concerns of their safety on health and long-term nicotine addiction remain unanswered due to a lack of studies that comprehensively evaluate their toxicity in the airways.

Moreover, ECs produce vapor mainly from propylene glycol (PG) or vegetable glycerin (VG) that are blended at different concentrations, making comprehensive testing more difficult.

The lack of consistent results demands a full evaluation of EC toxicity in the airway even when nicotine is not inhaled.

In our laboratory using cultures of primary normal human bronchial epithelial(NHBE) cells (either differentiating or fully differentiated) exposed to EC vapor or an equivalent volume of filtered air we have demonstrated that EC vapor can be delivered to fully differentiated NHBE cells and that high, but realistic puff numbers decrease ciliary beat frequency (CBF) as well as Large, Ca2+-activated K+ channels (BK channel) (the pore forming α subunit KCNMA1) and Forkhead box protein (FOXJ)-1 expression. We also have preliminary data of smoke exposure in vitro and in vivo, showing a negative effect of cigarette smoke and nicotine on parameters of mucociliary clearance (MCC) and nasal potential difference (NPD), a way to assess ion transport in vivo. These changes occurred in a TGF-β-dependent manner.

This study is designed to evaluate the airway toxicity of NFECs (Aim 2.1 of the project "Adverse effects of inhaled nicotine from tobacco and e-cigarettes").

PRIMARY ENDPOINT As the primary endpoint, we will assess the consequences of vaping EC liquid with no nicotine (NFEC) on cystic fibrosis transmembrane (CFTR)- and calcium-activated chloride channel (CaCC)-mediated chloride conductance in lifetime non-smokers using nasal potential difference (NPD) measurements.

We will use NPD as a primary endpoint because changes in most clinical parameters will only be seen after months or even years of exposure. For that particular reason, there is a recent surge to find alternative biomarkers that may be used as surrogate endpoints in shorter clinical trials. Since NPD directly measures the changes in ion transport expected to influence MCC and therefore overall outcome and since changes of NPD measurements are indirectly linked to lung function changes and MCC in trials with cystic fibrosis (CF) patients, we believe that NPD lends itself as a reasonable surrogate for MCC for this study.

SECONDARY ENDPOINTS Nasal nitric oxide and TGF-ß levels in nasal lavage and cells will be also collected to correlate with the changes on NPD results after exposure to NFEC.

STUDY DESIGN This aim will examine whether acute and subacute exposures to NFEC vapors have adverse effects on lifetime non-smokers by measuring changes in nasal ion transport and TGF-β levels. Nasal ion transport will be assessed by nasal potential difference (NPD), which measures the voltage potential resulting from epithelial ion fluxes (both Na+ absorption and Cl- and K+ secretion at the mucosal surface in vivo. In normal airway epithelia, Na+ absorption is the primary ion transport activity so that the resulting airway surface potential difference is negative with reference to the interstitium. Ion transport across nasal epithelia is representative for findings in distal airways. We also believe that NPD is a reasonably sensitive biomarker for this study as discussed below. Therefore, we will evaluate the acute effects of NFEC vapor generated from the nicotine-carrier system ("e-liquid" without nicotine) and the subacute effect after a 7-days exposure to the NFEC.

Since the major difference between the ECs is the amount of vapor produced per puff, we will focus on a commonly used mini and mid-sized EC: Halo (The Halo company, USA) and eGo-T® (Joyetech Co., Ltd., ShenZhen China), and examine different vapor fluids or "e-liquids" (100% PG, 50% PG/50% VG and 100% VG) without nicotine.

Eligibility criteria: Inclusion Criteria:

INCLUSION CRITERIA:

* Subjects will be over 18 years of age.
* Healthy life-time non-smokers

Exclusion Criteria:

* Presence of airflow obstruction (COPD, asthma, bronchiectasis)
* Other concomitant inflammatory pulmonary disorders
* Subjects with known pulmonary malignancies within 5 years
* Subjects with prior thoracic surgery
* Subjects with respiratory infection that required use of oral corticosteroids and/or antibiotics within the prior 3 months
* Subjects with allergies to study medications
* Subjects incapable of providing informed consent.

Primary outcomes:
measure: changes on nasal potential difference (NPD) measurements
timeFrame: before and after 7 days of vapor
Secondary outcomes:
measure: changes on nasal nitric oxide
timeFrame: before and after 7 days of vapor
measure: changes on TGF-ß levels in nasal lavage
timeFrame: before and after 7 days of vapor
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
Study officials:
affiliation: University of Miami
name: Michael Campos, MD
role: PRINCIPAL_INVESTIGATOR
References: