Melatonin in Smoke-induced Vascular Injury

Smoking Clinical Trial

Official title:

The Protective Effect of Melatonin on Smoke-induced Vascular Injury in Human

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02591238
• Other study ID #: 81470585
• Status: Completed
• Phase: Phase 4
• First received: October 26, 2015
• Last updated: February 3, 2016
• Start date: June 2015
• Est. completion date: October 2015

Study information

• Verified date: June 2015
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics CommitteeChina: National Natural Science Foundation
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: October 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 25 Years to 39 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Smoking
• Vascular System Injuries

Intervention

Other:
• non-smoker oral placebo
Participants oral placebo last 2 weeks.

Drug:
• non-smoker oral melatonin
Participants oral melatonin 3 mg/day last 2 weeks.

Other:
• smoker oral placebo
Participants oral placebo last 2 weeks.

Drug:
• smoker oral melatonin
Participants oral melatonin 3 mg/day last 2 weeks.

Locations

Country	Name	City	State
China	PekingUMCH	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (17)

Bernhard D, Pfister G, Huck CW, Kind M, Salvenmoser W, Bonn GK, Wick G. Disruption of vascular endothelial homeostasis by tobacco smoke: impact on atherosclerosis. FASEB J. 2003 Dec;17(15):2302-4. Epub 2003 Oct 2. — View Citation

Bonita R, Magnusson R, Bovet P, Zhao D, Malta DC, Geneau R, Suh I, Thankappan KR, McKee M, Hospedales J, de Courten M, Capewell S, Beaglehole R; Lancet NCD Action Group. Country actions to meet UN commitments on non-communicable diseases: a stepwise appro — View Citation

Hardeland R, Tan DX, Reiter RJ. Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines. J Pineal Res. 2009 Sep;47(2):109-26. doi: 10.1111/j.1600-079X.2009.00701.x. Epub 2009 Jul 1. Review. — View Citation

Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997 Sep 26;277(5334):2002-4. — View Citation

Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson RN, McAfee T, Peto R. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013 Jan 24;368(4):341-50. doi: 10.1056/NEJMsa1211128. — View Citation

Opie LH. The metabolic vicious cycle in heart failure. Lancet. 2004 Nov 13-19;364(9447):1733-4. — View Citation

Pirie K, Peto R, Reeves GK, Green J, Beral V; Million Women Study Collaborators. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet. 2013 Jan 12;381(9861):133-41. doi: 10.1016/S0140-673 — View Citation

Pope CA 3rd, Burnett RT, Krewski D, Jerrett M, Shi Y, Calle EE, Thun MJ. Cardiovascular mortality and exposure to airborne fine particulate matter and cigarette smoke: shape of the exposure-response relationship. Circulation. 2009 Sep 15;120(11):941-8. do — View Citation

Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology (Bethesda). 2014 Sep;29(5):325-33. doi: 10.1152/physiol.00011.2014. Review. — View Citation

Reiter RJ. Melatonin: Lowering the High Price of Free Radicals. News Physiol Sci. 2000 Oct;15:246-250. — View Citation

Rodella LF, Filippini F, Bonomini F, Bresciani R, Reiter RJ, Rezzani R. Beneficial effects of melatonin on nicotine-induced vasculopathy. J Pineal Res. 2010 Mar;48(2):126-32. doi: 10.1111/j.1600-079X.2009.00735.x. Epub 2009 Dec 30. — View Citation

Rostron BL, Chang CM, Pechacek TF. Estimation of cigarette smoking-attributable morbidity in the United States. JAMA Intern Med. 2014 Dec;174(12):1922-8. doi: 10.1001/jamainternmed.2014.5219. — View Citation

Tan DX, Hardeland R, Manchester LC, Galano A, Reiter RJ. Cyclic-3-hydroxymelatonin (C3HOM), a potent antioxidant, scavenges free radicals and suppresses oxidative reactions. Curr Med Chem. 2014;21(13):1557-65. — View Citation

Tan DX, Manchester LC, Reiter RJ, Plummer BF, Hardies LJ, Weintraub ST, Vijayalaxmi, Shepherd AM. A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vivo hydroxyl radical generation. Biochem Biophys Res Commun. 1998 Dec 30;253(3):6 — View Citation

Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, Diaz R, Rashed W, Freeman R, Jiang L, Zhang X, Yusuf S; INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. — View Citation

Yang GH, Li YC, Wang ZQ, Liu B, Ye W, Ni L, Zeng R, Miao SY, Wang LF, Liu CW. Protective effect of melatonin on cigarette smoke-induced restenosis in rat carotid arteries after balloon injury. J Pineal Res. 2014 Nov;57(4):451-8. doi: 10.1111/jpi.12185. Ep — View Citation

Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART s — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Fbg.		Three months	Yes
Primary	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of Glu.		Three months.	Yes
Primary	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of FFA.		Three months.	Yes
Primary	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TC.		Three months.	Yes
Primary	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of TG.		Three months.	Yes
Primary	Smoke-induced Vascular Injury and Melatonin's Effect in This Process Assessed by the Concentration of LDL-C.		Three months.	Yes