Melatonin in Patients Under Carotid Endarterectomy

Carotid Stenosis Clinical Trial

Official title:

The Protective Effect of Melatonin in Patients Under Carotid Endarterectomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03115034
• Other study ID #: LCW-ZS1057
• Status: Completed
• Phase: Phase 4
• First received: March 22, 2017
• Last updated: November 5, 2017
• Start date: June 1, 2016
• Est. completion date: November 1, 2017

Study information

• Verified date: March 2017
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the effects of melatonin in the regulation of the vascular injury in patients under carotid endarterectomy through population-based, randomized, double-blind, placebo-controlled trial.

Description:

Trial Title: The protective effect of melatonin in patients under carotid endarterectomy Protocol: Investigators recruited eligible Han Chinese participants (aged 40-80) who were diagnosed with carotid stenosis and had indications for carotid endarterectomy (CEA). Participants were excluded if participants had undergone surgical contraindication, or cardiovascular disease, or cerebral infarction within 3 months, or psychiatric disorders, or cancer, or pregnant, or lactating, or taking antipsychotic drugs during perioperative period. Participants were randomly divided into groups of CEA with oral melatonin, CEA with oral placebo, and CEA with blank control. Participants in groups of CEA with oral melatonin and CEA with oral placebo took melatonin orally 6mg/day or placebo from 3 days before operation to 3 days after operation. Blood samples (about 3 milliliter) were taken at baseline, 6h after the operation and 24h after the operation. Through a series hospital clinical laboratory and related ELISA kits to detect endothelial cell injury and ischemia reperfusion in serum markers. Superoxide dismutase (SOD), malonaldehyde (MDA), S100B protein, endothelial nitric oxide synthase (eNOS), nuclear erythroid 2-related factor 2 (Nrf - 2), Interleukin 6 (IL-6), nuclear transcription factor κB p65 (NF-κB p65) were included for analysis to verify whether melatonin have protective effect in patients under carotid endarterectomy. This trial is approved by the Ethical Committee of Peking Union Medical College Hospital (No ZS 1057). All participants completed a questionnaire and signed an informed consent document. Otherwise, participants 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 patients under CEA with placebo or blank, patients took melatonin have a lower vascular injury and ischemia reperfusion 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 40 to 80.

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. Participants guarantee to comply with the criterion before start of the trial. 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: 60
• Est. completion date: November 1, 2017
• Est. primary completion date: June 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• diagnosed with carotid stenosis

• had indications for carotid endarterectomy (CEA)

Exclusion Criteria:

• surgical contraindication

• cardiovascular disease

• cerebral infarction within 3 months

• psychiatric disorders

• cancer

• pregnant

• lactating

• taking antipsychotic drugs during perioperative period

Related Conditions & MeSH terms

• Carotid Stenosis

Intervention

Drug:
• Melatonin
Patients under CEA taking 6mg/day melatonin orally from 3 days before operation to 3 days after operation.
• placebo
Patients under CEA taking placebo orally from 3 days before operation to 3 days after operation.

Other:
• blank
Patients under CEA without taking melatonin or placebo

Locations

Country	Name	City	State
China	Changwei Liu	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Andersen LP, Rosenberg J, Gögenur I. Perioperative melatonin: not ready for prime time. Br J Anaesth. 2014 Jan;112(1):7-8. doi: 10.1093/bja/aet332. — View Citation

Cervantes M, Moralí G, Letechipía-Vallejo G. Melatonin and ischemia-reperfusion injury of the brain. J Pineal Res. 2008 Aug;45(1):1-7. doi: 10.1111/j.1600-079X.2007.00551.x. Epub 2008 Jan 9. Review. — View Citation

Cheng L, Jin Z, Zhao R, Ren K, Deng C, Yu S. Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway. Int J Clin Exp Med. 2015 Jul 15;8(7):10420-8. eCollection 2015. — View Citation

Ge YL, Li X, Gao JU, Zhang X, Fang X, Zhou L, Ji W, Lin S. Beneficial effects of intravenous dexmedetomidine on cognitive function and cerebral injury following a carotid endarterectomy. Exp Ther Med. 2016 Mar;11(3):1128-1134. Epub 2016 Jan 11. — View Citation

Kalimeris K, Kouni S, Kostopanagiotou G, Nomikos T, Fragopoulou E, Kakisis J, Vasdekis S, Matsota P, Pandazi A. Cognitive function and oxidative stress after carotid endarterectomy: comparison of propofol to sevoflurane anesthesia. J Cardiothorac Vasc Anesth. 2013 Dec;27(6):1246-52. doi: 10.1053/j.jvca.2012.12.009. Epub 2013 May 30. — View Citation

Kalra VB, Rao B, Malhotra A. Teaching NeuroImages: perfusion imaging of cerebral hyperperfusion syndrome following revascularization. Neurology. 2013 Jul 23;81(4):e25-6. doi: 10.1212/WNL.0b013e31829c5cae. — View Citation

Lapi D, Vagnani S, Cardaci E, Paterni M, Colantuoni A. Rat pial microvascular responses to melatonin during bilateral common carotid artery occlusion and reperfusion. J Pineal Res. 2011 Aug;51(1):136-44. doi: 10.1111/j.1600-079X.2011.00870.x. Epub 2011 Apr 7. — View Citation

Lieb M, Shah U, Hines GL. Cerebral hyperperfusion syndrome after carotid intervention: a review. Cardiol Rev. 2012 Mar-Apr;20(2):84-9. doi: 10.1097/CRD.0b013e318237eef8. Review. — View Citation

Pärsson HN, Lord RS, Scott K, Zemack G. Maintaining carotid flow by shunting during carotid endarterectomy diminishes the inflammatory response mediating ischaemic brain injury. Eur J Vasc Endovasc Surg. 2000 Feb;19(2):124-30. — View Citation

Walsh SR, Nouraei SA, Tang TY, Sadat U, Carpenter RH, Gaunt ME. Remote ischemic preconditioning for cerebral and cardiac protection during carotid endarterectomy: results from a pilot randomized clinical trial. Vasc Endovascular Surg. 2010 Aug;44(6):434-9. doi: 10.1177/1538574410369709. Epub 2010 May 18. — View Citation

Wang Z, Ni L, Wang J, Lu C, Ren M, Han W, Liu C. The protective effect of melatonin on smoke-induced vascular injury in rats and humans: a randomized controlled trial. J Pineal Res. 2016 Mar;60(2):217-27. doi: 10.1111/jpi.12305. Epub 2016 Jan 13. — View Citation

Weigand MA, Laipple A, Plaschke K, Eckstein HH, Martin E, Bardenheuer HJ. Concentration changes of malondialdehyde across the cerebral vascular bed and shedding of L-selectin during carotid endarterectomy. Stroke. 1999 Feb;30(2):306-11. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Melatonin effects on patients under CEA assessed by the concentration of SOD	Melatonin effects on patients under CEA are detected by the concentration of SOD by ELISA kit.	3 months
Primary	Melatonin effects on patients under CEA assessed by the concentration of MDA	Melatonin effects on patients under CEA are detected by the concentration of MDA by ELISA kit.	3 months
Primary	Melatonin effects on patients under CEA assessed by the concentration of S100b	Melatonin effects on patients under CEA are detected by the concentration of S100b by ELISA kit.	3 months
Primary	Melatonin effects on patients under CEA assessed by the concentration of eNOS	Melatonin effects on patients under CEA are detected by the concentration of eNOS by ELISA kit.	3 months
Primary	Melatonin effects on patients under CEA assessed by the concentration of Nrf-2	Melatonin effects on patients under CEA are detected by the concentration of Nrf-2 by ELISA kit.	3 months
Primary	Melatonin effects on patients under CEA assessed by the concentration of IL-6	Melatonin effects on patients under CEA are detected by the concentration of IL-6 by ELISA kit.	3 months
Primary	Melatonin effects on patients under CEA assessed by the concentration of NF-?B p65	Melatonin effects on patients under CEA are detected by the concentration of NF-?B p65 by ELISA kit.	3 months