Clinical trial NCT02591238: Melatonin in Smoke-induced Vascular Injury
Official title: The Protective Effect of Melatonin on Smoke-induced Vascular Injury in Human
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Smoking
Vascular System Injuries
Keywords: smoking
melatonin
vascular injury
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2015-10-29
Enrollment: 68
Sex: ALL
Minimum age (years): 25
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main purpose of this study was to evaluate the effects of melatonin in the regulation of the vascular injury in smokers through population-based, randomized, double-blind, placebo-controlled trial.

Detailed description: Trial title: The protective effect of melatonin on smoke-induced vascular injury in human

Protocol: Investigators recruited eligible Han Chinese participants (aged 25-39) if they had smoking at least 10 cigarettes per day for at least 1 year. Participants excluded if they had undergone cardiovascular disease, or systolic blood pressure above 140 mm Hg, or diastolic blood pressure above 90 mmHg, or psychiatric disorders, or cancer, or pregnant, or lactating, or taking antipsychotic drugs orally during the 2 weeks of the trial. They were randomly divided participants into non-smoking with oral placebo, non-smoking with oral melatonin, smoking with oral placebo, and smoking with oral melatonin. They are oral melatonin 3 mg/day or placebo for 2 weeks. Blood samples (about 3 milliliter) were taken at baseline and after 2 weeks of treatment. Through a series hospital clinical laboratory and related ELISA kits to detect endothelial cell injury in serum markers platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31)， intercellular adhesion molecule-1 (ICAM - 1), vascular cell adhesion molecule-1 (VCAM 1), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), nuclear erythroid 2-related factor 2 (Nrf - 2), NAD(P)H quinone oxidoreductase-1 (NQO-1), catalytic glutamate cysteine ligase (GCLC), heme oxygenase-1 (HO-1), free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), hypersensitive c-reactive protein (hsCRP), fibrinogen (Fbg), and free fatty acids (FFA), through the above vascular endothelial damage index analysis whether melatonin have protective effect against smoke-induced vascular injury. All participants and study investigators were unaware of treatment allocation throughout the trial. This trial is approved by the Ethical Committee of Peking Union Medical College Hospital (No JS-863). All participants completed a questionnaire and signed an informed consent document. Otherwise, they will get appropriate economic compensation. To achieve treatment concealment, melatonin and placebo in appearance and package were identically. Trial associates monitored compliance with the masking procedure throughout the trial. All participants and study investigators were unaware of treatment allocation throughout the study. The randomization codes remained sealed until after data collection and cleaning, and completion of a masked analysis. The study team monitored and classified protocol deviations. Investigators summarized baseline clinical and demographic characteristics with descriptive statistics and then determined by the Univariate Analysis of Variance. All the data analyses were done using statistical software SPSS 20.0.

Expected results: Compared with smoker oral placebo, melatonin 3 mg/day may be alleviate smoke-induced vascular injury.

Consent document: The potential risk, research as a treatment drug of melatonin may delay the metabolism of antipsychotic antipsychotic drug, so when investigators recruit psychiatric disorders or taking antipsychotic drugs orally during the 2 weeks of the trial should exclusion. As a Health care medicine. Melatonin is not suitable for children, so investigators selected recruiting participants under the age of 25 to 39.

The measure to minimize the risk, fully inform the participants and their families the trial's advantages, disadvantages and desired effect. All participants totally agree with the subjects. In this process, at least three or more effective way to get contact with the medical staff or doctor and ensure that those unexpected accident should deserve effective tackle. Examination for every participant before start of the trial to guarantee they comply with the criterion. Our research involves the application of melatonin is through the china food and drug administration (CFDA) approved to ensure its safety (include its chemical composition, structure, content parameters, main raw material and appropriate crowd). All staff is qualified medical professionals to guarantee the safety of all participants.

The potential risks or discomfort, or inconvenience, or benefits for participants: So far, effective of melatonin in human include regulating sleep, anti-tumor, immune regulation, regulating of inflammation and immune and regulating blood lipid metabolism is confirmed. Adverse reactions is slow the delay of antipsychotic drug metabolism (so nearly one month ago and during period of the trial participants should not taking antipsychotic drugs) during the trial. The basic principle during the trial is ensure safety of participants.

The relevant content consultation: Everyone have the right to consultation the research content through telephone: +86 01069152500 (principal investigator) and +86 01069155817(Ethics committee).

The rights of withdrew from the trial: Participate in the trial is completely voluntary. If for any reason, participants not willing to participate in, or do not wish to continue to participate in this trial, will not affect the rights and interests of participants. In addition, participants have the right to withdraw this trial at any time. If participants do not according to the doctor instructions, or for the sake of your health and benefits, the doctor or the researchers may also require participants to quit the trial.

The compensation of research: If the participants have any unexpected accident relation with the trial, the compensation and responsibility will be provided by Peking union medical college hospital.

Privacy protection: The privacy of every participant will be protected. The results of the trial in academic publications will not leak any information to identify your personal identity. Peking union medical college hospital will save everybody's data and guarantee not leak without authorization.

Investigators declare no competing interests.

Eligibility criteria: Inclusion Criteria:

* Healthy smokers：must above 10 cigarettes per day, at least 1 year
* Healthy non-smokers

Exclusion Criteria:

* Cardiovascular disease
* Systolic blood pressure above 140 mm Hg
* Diastolic blood pressure above 90 mmHg
* Psychiatric disorders
* Cancer
* Pregnant
* Lactating
* Taking antipsychotic drugs orally during the 2 weeks of the trial

Primary outcomes:
measure: Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Fbg.
timeFrame: Three months
measure: Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Glu.
timeFrame: Three months.
measure: Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of FFA.
timeFrame: Three months.
measure: Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TC.
timeFrame: Three months.
measure: Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TG.
timeFrame: Three months.
measure: Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of LDL-C.
timeFrame: Three months.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: PekingUMCH
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Changwei Liu, MD
role: PRINCIPAL_INVESTIGATOR
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