Melatonin and Risk Of Cardiovascular Events And Malignant Tumors In The Elderly

NCT ID: NCT04631341

Last Updated: 2020-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

10000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-01

Study Completion Date

2026-12-31

Brief Summary

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Cardiovascular diseases and tumors seriously threaten human health. There are many risk factors that affect the occurrence and death of cardiovascular diseases and malignant tumors. In addition to genetic and congenital factors, it also includes bad lifestyles, such as smoking, drinking, abnormal metabolism, excessive stress, etc. Many factors such as excessive stress and staying up late can cause abnormal circadian rhythms. The regulation of circadian rhythm is likely to be a key key to the early prevention of cardiovascular diseases and tumors.

Melatonin has an important role in regulating the circadian rhythm of the human body. The latest research of our research group confirmed that melatonin can reduce the level of oxidative stress through the retinoic acid-related orphan nuclear receptor alpha (RORα) and thereby inhibit pathological cardiac hypertrophy; melatonin can regulate the polarization and polarization of macrophages RORα receptor stabilizes vulnerable plaque in arteries and prevents plaque rupture.

In China, melatonin is widely used in the market as a health product. However, the protective mechanism of melatonin in cardiovascular diseases and tumors is still unclear, and large-scale population intervention studies are still lacking. The level of melatonin in the daytime changes little with age, but the peak at night gradually decreases with age. In people aged 60 and above, the peak of melatonin at night decreased significantly. We speculate that melatonin supplementation may be able to reduce the oxidative damage of mitochondria by maintaining the level of melatonin at night in the body, delay cell decay, and delay this physiological process.

Therefore, the project team intends to combine the developed new cardiovascular disease and tumor risk prediction models in the Shanghai elderly cohort established in the early stage, and randomize groups of healthy people in the same risk stratification, according to whether or not to supplement melatonin. There are two cohorts: the melatonin intervention cohort and the parallel control cohort. By observing the efficacy indicators of cardiovascular disease and tumor incidence in the two groups during the follow-up period, it provides evidence-based medical evidence for the future clinical application of melatonin.

Detailed Description

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Cardiovascular diseases and tumors seriously threaten human health. With the aging of the population in my country, the number of patients with two diseases has been increasing year by year, the difficulty of treatment has greatly increased, and the prognosis of most patients is poor. Therefore, it is of great clinical significance to explore safe and effective intervention programs to prevent cardiovascular diseases and malignant tumors in the elderly.

There are many risk factors that affect the occurrence and death of cardiovascular diseases and malignant tumors. In addition to genetic and congenital factors, it also includes bad lifestyles, such as smoking, drinking, abnormal metabolism, excessive stress, etc. Many factors such as excessive stress and staying up late can cause abnormal circadian rhythms \[5, 6\]. The regulation of circadian rhythm is likely to be a key key to the early prevention of cardiovascular diseases and tumors.

Melatonin has an important role in regulating the circadian rhythm of the human body. A number of basic and clinical studies at home and abroad have shown that melatonin has a protective effect on inhibiting cardiovascular disease and tumor occurrence. The latest research of our research group confirmed that melatonin can reduce the level of oxidative stress through the retinoic acid-related orphan nuclear receptor alpha (RORα) and thereby inhibit pathological cardiac hypertrophy; melatonin can regulate the polarization and polarization of macrophages RORα receptor stabilizes vulnerable plaque in arteries and prevents plaque rupture.

In China, melatonin is widely used in the market as a health product. Melatonin has a wide range of sources, no obvious toxic and side effects to the body, and high bioavailability, which suggests that it can prevent cardiovascular diseases and It has important potential in the occurrence of tumors. However, the protective mechanism of melatonin in cardiovascular diseases and tumors is still unclear, and large-scale population intervention studies are still lacking. The level of melatonin in the daytime changes little with age, but the peak at night gradually decreases with age. In people aged 60 and above, the peak of melatonin at night decreased significantly. We speculate that melatonin supplementation may be able to reduce the oxidative damage of mitochondria by maintaining the level of melatonin at night in the body, delay cell decay, and delay this physiological process.

Therefore, the project team intends to combine the developed new cardiovascular disease and tumor risk prediction models in the Shanghai elderly cohort established in the early stage, and randomize groups of healthy people in the same risk stratification, according to whether or not to supplement melatonin. There are two cohorts: the melatonin intervention cohort and the parallel control cohort. By observing the efficacy indicators of cardiovascular disease and tumor incidence in the two groups during the follow-up period, it provides evidence-based medical evidence for the future clinical application of melatonin.

Conditions

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Cardiovascular Diseases

Keywords

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Cohort study Natural Population China

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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Melatonin Group

Take melatonin supplements

Group Type EXPERIMENTAL

Melatonin

Intervention Type DIETARY_SUPPLEMENT

Melatonin 5mg every night, for one year

Normal Control Group

Don't take melatonin supplements

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Melatonin

Melatonin 5mg every night, for one year

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

1. Queue members;
2. Han nationality;
3. Between 60-74 years old, no gender limit;
4. Women are in menopause;
5. Patients without a history of malignant tumors (except for non-melanoma skin cancer), myocardial infarction, stroke, transient ischemic attack (TIA), angina, coronary artery bypass graft (CABG) or Percutaneous Coronary Intervention;
6. No mental illness;
7. No history of supplement allergy or supplement allergy;
8. Subjects voluntarily participate in this study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria

1. People who have difficulty swallowing or have known supplementary malabsorption;
2. Have received any other clinical trial treatment within 1 year;
3. The subject has a known, active or suspicious autoimmune disease;
4. The subject has severe infections, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.;
5. The subject has used a live attenuated vaccine in the past 30 days;
6. The subject has been taking antidepressant medication before or is taking;
7. Use of anticoagulants at baseline, history of kidney stones, renal failure or dialysis, hypercalcemia, hypoparathyroidism or hyperthyroidism, severe liver disease (cirrhosis), sarcoidosis or other granulomatous diseases, such as Active chronic tuberculosis or Wegener's granulomatosis, dementia, epilepsy, rheumatoid arthritis, sleep apnea syndrome, alcoholism;
8. Situations deemed unsuitable by other researchers.
Minimum Eligible Age

60 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role collaborator

Tongji Hospital

OTHER

Sponsor Role collaborator

Huadong Hospital

OTHER

Sponsor Role collaborator

ShuGuang Hospital

OTHER

Sponsor Role collaborator

RenJi Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jun Pu

Director of Cardiovascular Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jun Pu, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

RenJi Hospital

Central Contacts

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Jun Pu, MD,PhD

Role: CONTACT

Phone: 86-21-68383477

Email: [email protected]

Song Ding, MD,PhD

Role: CONTACT

References

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Xu L, Su Y, Zhao Y, Sheng X, Tong R, Ying X, Gao L, Ji Q, Gao Y, Yan Y, Yuan A, Wu F, Lan F, Pu J. Melatonin differentially regulates pathological and physiological cardiac hypertrophy: Crucial role of circadian nuclear receptor RORalpha signaling. J Pineal Res. 2019 Sep;67(2):e12579. doi: 10.1111/jpi.12579. Epub 2019 Apr 24.

Reference Type BACKGROUND
PMID: 30958896 (View on PubMed)

Ding S, Lin N, Sheng X, Zhao Y, Su Y, Xu L, Tong R, Yan Y, Fu Y, He J, Gao Y, Yuan A, Ye L, Reiter RJ, Pu J. Melatonin stabilizes rupture-prone vulnerable plaques via regulating macrophage polarization in a nuclear circadian receptor RORalpha-dependent manner. J Pineal Res. 2019 Sep;67(2):e12581. doi: 10.1111/jpi.12581. Epub 2019 May 14.

Reference Type BACKGROUND
PMID: 31009101 (View on PubMed)

Zhao Y, Xu L, Ding S, Lin N, Ji Q, Gao L, Su Y, He B, Pu J. Novel protective role of the circadian nuclear receptor retinoic acid-related orphan receptor-alpha in diabetic cardiomyopathy. J Pineal Res. 2017 Apr;62(3). doi: 10.1111/jpi.12378. Epub 2017 Feb 22.

Reference Type BACKGROUND
PMID: 27862268 (View on PubMed)

Zhao YC, Xu LW, Ding S, Ji QQ, Lin N, He Q, Gao LC, Su YY, Pu J, He B. Nuclear receptor retinoid-related orphan receptor alpha deficiency exacerbates high-fat diet-induced cardiac dysfunction despite improving metabolic abnormality. Biochim Biophys Acta Mol Basis Dis. 2017 Aug;1863(8):1991-2000. doi: 10.1016/j.bbadis.2016.10.029. Epub 2016 Nov 5.

Reference Type BACKGROUND
PMID: 27825849 (View on PubMed)

He B, Zhao Y, Xu L, Gao L, Su Y, Lin N, Pu J. The nuclear melatonin receptor RORalpha is a novel endogenous defender against myocardial ischemia/reperfusion injury. J Pineal Res. 2016 Apr;60(3):313-26. doi: 10.1111/jpi.12312. Epub 2016 Feb 16.

Reference Type BACKGROUND
PMID: 26797926 (View on PubMed)

Other Identifiers

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Melatonin Intervention Study

Identifier Type: -

Identifier Source: org_study_id