Hookah Smoking, Carbon Monoxide, and Coronary Endothelial Function

NCT03166787 | Terminated Phase 1 FDA Drug

• 2 other identifiers: Protocol 47441R21DA041596
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Hookah (water pipe) smoking is a new global epidemic. The World Health Organization wants to prohibit all claims that hookah is less harmful than cigarettes and wants hookah products to bear the same warning labels as cigarettes. But there is little scientific evidence to substantiate this proposal. Cigarettes, cigars, medicinal nicotine, and e-cigarettes all acutely impair brachial artery endothelial function (flow-mediated dilation, FMD). Also, cigarettes cause both acute and chronic impairment in coronary endothelial function, but the comparative effects of hookah are unknown. Hookah tobacco is heated with burning charcoal. So, the smoke contains "tar" and nicotine plus charcoal combustion products. These include carbon monoxide (CO) and proatherogenic oxidants (especially carbon-rich nanoparticles) that the study team expected to impair endothelial function.

Conditions

Smoking; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (1)

• the change in Myocardial Blood Flow.

  the change in Myocardial Blood Flow between Baseline and post intervention.

  90 minute

Study Arms (3)

Myocardial Blood Flow

EXPERIMENTAL

Myocardial contrast echocardiography will be used to measure regional myocardial perfusion .

Other: Charcoal hookah; Other: E-coal hookah; Other: Cigarette

Assess Coronary Endothelial Function

EXPERIMENTAL

young hookah smokers will be randomized to have coronary endothelial function assessed before and after inhaling Carbon Monoxide or room air from a Douglas bag.

Drug: Carbon Monoxide inhalation; Other: Room Air inhalation

Test coronary endothelial function

EXPERIMENTAL

Test coronary endothelial function before after hookah smokers smoke charcoal-heated hookah and before and after age-matched cigarette smokers smoke 2 cigarettes. In the same subjects, we will test for acute smoking-induced changes in LV wall strain by speckle tracking. Finally, in a subset of subjects we will repeat the MCE and speckle tracking studies after pretreatment with either i.v. vitamin C or one dose of oral tadalafil.

Drug: vitamin C; Drug: tadalafil

Interventions

Charcoal hookah OTHER

The Myocardial Blood Flow (MBF) will be measured at rest and during the last minute of a 3-minute bout of handgrip at 30% Maximal voluntary contraction. This sequence will be performed before and after 12 young hookah smokers are randomized to smoke the same popular Starbuzz tobacco product heated with either charcoal for 30 min each.

Myocardial Blood Flow

E-coal hookah OTHER

The Myocardial Blood Flow (MBF) will be measured at rest and during the last minute of a 3-minute bout of handgrip at 30% Maximal voluntary contraction. This sequence will be performed before and after 12 young hookah smokers are randomized to smoke the same popular Starbuzz tobacco product heated with electrically (Global First "e-coal," ) for 30 min each.

Myocardial Blood Flow

Cigarette OTHER

The Myocardial Blood Flow (MBF) will be measured at rest and during the last minute of a 3-minute bout of handgrip at 30% Maximal voluntary contraction. This sequence will be performed before and after 12 young cigarette smokers smoke 2 cigarettes down to the stub over 30 min (to simulate real-world use).

Myocardial Blood Flow

Carbon Monoxide inhalation DRUG

A subset (n=8) of the young hookah smokers will return on a later day and will be randomized to have coronary endothelial function assessed before and after inhaling 0.3 CO gas from a Douglas bag.

Assess Coronary Endothelial Function

Room Air inhalation OTHER

A subset 8 of the young hookah smokers will return on a later day and will be randomized to have coronary endothelial function assessed before and after inhaling room air from a Douglas bag.

Assess Coronary Endothelial Function

vitamin C DRUG

in a subset of 6 subjects the study team will repeat the Myocardial Contrast Echocardiography and speckle tracking studies after pretreatment with either i.v. vitamin C .

Test coronary endothelial function

tadalafil DRUG

in a subset of 6 subjects the study team will repeat the Myocardial Contrast Echocardiography and speckle tracking studies after pretreatment with one dose of oral tadalafil.

Test coronary endothelial function

Eligibility Criteria

• Age: 21 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• y/o hookah smokers: smoked hookah \> 12 times in the last 12 months.
• y/o cigarette smokers: smoked \>100 cigarettes and smoked in the last 30 days.
• y/o hookah smokers: smoke hookah at least once per week for \> 20 years.
• y/o cigarette smokers: have \> 20 pack-year cigarette smoking history.
• All subjects must have:
• no history of illicit drug use or marijuana.
• no evidence of cardiopulmonary disease by history or physical.
• no diabetes with fasting blood glucose \<100 mg/dl.
• BP\<140/90 mmHg.
• resting heart rate\<100 bpm.
• BMI\<30kg•m2.
• no prescription medication.
• normal EKG and echocardiogram.

You may not qualify if:

• suboptimal echocardiographic window.
• exhaled CO\>10 ppm (smoking non-abstinence).
• positive pregnancy test.
• psychiatric illness.
• other conditions deemed unsafe to participate.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Smoking

Interventions

Tobacco Products; Ascorbic Acid; Tadalafil

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Ronald Victor, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician I

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: May 25, 2017
• Study Start: August 15, 2017
• Primary Completion: April 15, 2020
• Study Completion: October 15, 2020
• Last Updated: April 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)