Melatonin in Smoke-induced Vascular Injury

• Sponsor: Peking Union Medical College Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02591238
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 4
• Duration (Months): 4
• Patients Per Site Per Month: 17

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Smoking; Vascular System Injuries	Other: non-smoker oral placebo; Drug: non-smoker oral melatonin; Other: smoker oral placebo; Drug: smoker oral melatonin	Phase 4

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: [phone] (principal investigator) and [phone](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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Protective Effect of Melatonin on Smoke-induced Vascular Injury in Human
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: non-smoker + placebo non-smoker oral placebo	Other: non-smoker oral placebo; Participants oral placebo last 2 weeks.; Other Names: placebo
Active Comparator: non-smoker + melatonin non-smoker oral melatonin	Drug: non-smoker oral melatonin; Participants oral melatonin 3 mg/day last 2 weeks.; Other Names: Melatonin
Placebo Comparator: smoker + placebo smoker oral placebo	Other: smoker oral placebo; Participants oral placebo last 2 weeks.; Other Names: placebo
Active Comparator: smoker + melatonin smoker oral melatonin	Drug: smoker oral melatonin; Participants oral melatonin 3 mg/day last 2 weeks.; Other Names: melatonin

Outcome Measures

Primary Outcome Measures

1. Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Fbg. [Three months]

2. Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Glu. [Three months.]

3. Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of FFA. [Three months.]

4. Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TC. [Three months.]

5. Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TG. [Three months.]

6. Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of LDL-C. [Three months.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 39 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PekingUMCH	Beijing	Beijing	China	100730

Sponsors and Collaborators

• Peking Union Medical College Hospital

Investigators

• Principal Investigator: Changwei Liu, MD, Peking Union Medical College Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Peking Union Medical College Hospital
• ClinicalTrials.gov Identifier: NCT02591238
• Other Study ID Numbers: 81470585
• First Posted: Oct 29, 2015
• Last Update Posted: Mar 3, 2016
• Last Verified: Jun 1, 2015

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Peking Union Medical College Hospital: smoking; melatonin; vascular injury
• Additional relevant MeSH terms: Vascular System Injuries; Wounds and Injuries; Melatonin

Study Results

Participant Flow

Recruitment Details	Time: Jun 10,2015 -Jun 24,2015. Address: factory clinic of Heilongjiang Airports Managements Group Co., Ltd and village clinic of Xinfa village Daoli district, Haerbin city, Heilongjiang province, China. Medical staff: 3 Registered medical practitioner and 4 registered nurse.
Pre-assignment Detail	First in included 96 participants of both genders, 28 participants excluded (refused to randomly assigned n=9, not meeting inclusion criteria n=9, time improper n=8, unknown n=2). 5 participants withdraw during the trial (pregnant n=1, influenza n=1, personal circumstance n=2, unknown reason n=1).

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Period Title: Overall Study
STARTED	16	17	17	18
COMPLETED	15	16	17	15
NOT COMPLETED	1	1	0	3

Baseline Characteristics

Arm/Group Title	IVnon-smoker + Placebo	IIInon-smoker + Melatonin	IIsmoker + Placebo	Ismoker + Melatonin	Total
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	Total of all reporting groups
Overall Participants	15	16	17	15	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.5 (3.4)	34.6 (3.8)	31.7 (3.4)	31.7 (2.8)	33.37 (3.1)
Sex: Female, Male (Count of Participants)
Female	9 60%	10 62.5%	14 82.4%	13 86.7%	46 73%
Male	6 40%	6 37.5%	3 17.6%	2 13.3%	17 27%

Outcome Measures

1. Primary Outcome

Title	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Fbg.
Time Frame	Three months

Outcome Measure Data

Analysis Population Description

Bellow concentration data of Fbg was after treatment with oral melatonin 2 weeks.

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Measure Participants	15	16	17	15
Mean (Standard Deviation) [g/L]	2.76 (0.34)	2.38 (0.43)	2.89 (0.58)	2.49 (0.54)

2. Primary Outcome

Title	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Glu.
Time Frame	Three months.

Outcome Measure Data

Analysis Population Description

Bellow concentration data of Glu was after treatment with oral melatonin 2 weeks.

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Measure Participants	15	16	17	15
Mean (Standard Deviation) [mmol/L]	4.4 (1.36)	4.24 (1.3)	5.02 (1.26)	4.79 (1.05)

3. Primary Outcome

Title	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of FFA.
Time Frame	Three months.

Outcome Measure Data

Analysis Population Description

Below concentration data of FFA was after treatment with oral melatonin 2 weeks.

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Measure Participants	15	16	17	15
Mean (Standard Deviation) [umol/L]	389 (121)	382 (49)	499 (84)	425 (64)

4. Primary Outcome

Title	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TC.
Time Frame	Three months.

Outcome Measure Data

Analysis Population Description

Bellow concentration data of TC was after treatment with oral melatonin 2 weeks.

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Measure Participants	15	16	17	15
Mean (Standard Deviation) [mmol/L]	4.51 (1.04)	4.5 (0.95)	4.74 (0.8)	4.45 (0.65)

5. Primary Outcome

Title	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TG.
Time Frame	Three months.

Outcome Measure Data

Analysis Population Description

Bellow concentration data of TG was after treatment with oral melatonin 2 weeks.

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Measure Participants	15	16	17	15
Mean (Standard Deviation) [mmol/L]	1.21 (0.55)	1.23 (0.6)	1.42 (0.74)	1.41 (0.51)

6. Primary Outcome

Title	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of LDL-C.
Time Frame	Three months.

Outcome Measure Data

Analysis Population Description

Bellow concentration data of LDL-C was after treatment with oral melatonin 2 weeks.

Arm/Group Title	IV Non-smoker + Placebo	III Non-smoker + Melatonin	II Smoker + Placebo	I Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.	non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.	smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.	smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
Measure Participants	15	16	17	15
Mean (Standard Deviation) [mmol/L]	1.85 (0.54)	1.95 (0.52)	2.2 (0.75)	2.19 (0.47)

Adverse Events

Time Frame	Any adverse reaction symptoms of all participants were observed for three months.
Adverse Event Reporting Description	All participants did not have any adverse reactions during the three month period.
Arm/Group Title	Non-smoker + Placebo		Non-smoker + Melatonin		Smoker + Placebo		Smoker + Melatonin
Arm/Group Description	non-smoker oral placebo non-smoker oral placebo: Participants oral placebo last 2 weeks.		non-smoker oral melatonin non-smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.		smoker oral placebo smoker oral placebo: Participants oral placebo last 2 weeks.		smoker oral melatonin smoker oral melatonin: Participants oral melatonin 3 mg/day last 2 weeks.
All Cause Mortality
	Non-smoker + Placebo		Non-smoker + Melatonin		Smoker + Placebo		Smoker + Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Non-smoker + Placebo		Non-smoker + Melatonin		Smoker + Placebo		Smoker + Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)		0/17 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Non-smoker + Placebo		Non-smoker + Melatonin		Smoker + Placebo		Smoker + Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)		0/17 (0%)		0/15 (0%)

Limitations/Caveats

Limitations. First, the dose-dependent manner of melatonin should be considered. Second, the duration of smoke exposure and melatonin administration time should be prolonged. Lastly,the levels of melatonin at different time points should be examined.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.