Effect of Esketamine on Postoperative Sleep in Postmenopausal Women

NCT07315074 | Not Yet Recruiting DMC

• 1 other identifier: 20251115
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 2

Brief Summary

The prevalence of sleep disturbance among postmenopausal women has been reported to reach 51.6%. Epidemiological studies consistently show that the incidence of sleep disorders increases with age and menopausal transition. Compared with premenopausal women, postmenopausal women demonstrate reduced circadian rhythm stability and a higher prevalence of sleep disturbance. In this population, levels of melatonin, total sleep time, sleep latency, N3 stage sleep, and the circadian amplitude of alertness are all diminished. Sleep disturbance can adversely affect both the mental and physical health of women and significantly impair their social functioning. Poor sleep is associated with decreased cognitive performance and heightened emotional distress, contributing to diminished quality of life. Circadian rhythms are endogenous physiological and behavioral cycles that oscillate over approximately 24 hours, governing critical processes such as sleep-wake cycles, hormonal fluctuations (e.g., cortisol and melatonin). These rhythms are regulated by the suprachiasmatic nucleus (SCN). Disruptions in circadian rhythms have been associated with sleep disturbances. Esketamine is the S (+) enantiomer of ketamine and has a higher affinity for the NMDA receptor than the R-enantiomer. Previous studies have demonstrated that intraoperative administration of esketamine can improve postoperative sleep quality and reduce the incidence of postoperative sleep disturbances, through its antidepressant efficacy, anti-inflammatory properties, analgesic efficacy, neurocognitive and anxiolytic effects. However, few studies have investigated whether esketamine can regulate perioperative circadian rhythms and subsequently affect sleep, especially in postmenopausal women. The objective of this multi-center, prospective, randomized controlled clinical trial is to investigate the effects of esketamine on postoperative sleep in postmenopausal women.

Conditions

Circadian Rhythm; Postoperative Sleep Disturbance

Keywords

Esketamine; Circadian Rhythm; Melatonin; Postoperative Sleep Disturbance; Postmenopause

Outcome Measures

Primary Outcomes (1)

• The incidence of postoperative sleep disturbance (PSD) on postoperative day 1.

  The primary outcome is the incidence of PSD, evaluated using the Numeric Rating Scale (NRS) and the Athens Insomnia Scale (AIS) on postoperative day 1. PSD is defined as an NRS score of 6 or higher or an AIS score of 6 or higher.

  Postoperative day 1.

Secondary Outcomes (8)

• Biological rhythm detection

  From preoperative day 1 to postoperative day 3.

• Objective sleep parameters recorded by actigraphy

  From preoperative night 1 to postoperative night 3.

• Subjective sleep quality

  From preoperative day 1 to postoperative day 30.

• Anxiety and Depression assessments

  From preoperative day 1 to postoperative day 3.

• Frontal electroencephalography

  From entering the operating room to surgery ending.

Other Outcomes (3)

• Possible adverse reactions

  From esketamine infusion to postoperative day 3.

• Quality of postoperative recovery

  From postoperative day 1 to day 3.

• The length of hospital stay

  From the date of hospital admission to the date of discharge.

Study Arms (2)

Esketamine Group (Group E)

EXPERIMENTAL

Drug: Esketamine

Control Group (Group C)

PLACEBO COMPARATOR

Drug: Normal Saline

Interventions

Esketamine DRUG

Participants in Group E are administered esketamine with an infusion dose of 0.1 ml·kg-¹·h-¹ (0.2 mg·kg-¹·h-¹, diluted with 0.9% sodium chloride in a 2 mg/mL.

Esketamine Group (Group E)

Normal Saline DRUG

In Group C, 0.9% sodium chloride with a maintenance dose of 0.1 ml·kg-¹·h-¹ are administered intravenously.

Control Group (Group C)

Eligibility Criteria

• Age: 45 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists (ASA) physical status I-III.
• Aged ≥ 45 years.
• Women with natural menopause (aged ≥ 45 years and postmenopause for more than 12 months without surgical or medical intervention) .
• Scheduled to undergo elective lower-limb fracture surgery with an expected duration of more than 60 min under general anesthesia.
• Body Mass Index (BMI) between 18 and 28 kg/m².

You may not qualify if:

• Presence of preoperative sleep-related disorders, such as obstructive sleep apnea or restless legs syndrome.
• History of drug or alcohol abuse or dependence.
• Known contraindications or allergies to esketamine or other anesthetic agents.
• Use of psychotropic medications or sex hormones within the past 3 months.
• Shift work or taking medications affecting melatonin.
• Severe comorbid conditions, including but not limited to uncontrolled hypertension, coronary artery disease, cardiac insufficiency, pulmonary hypertension, intracranial hypertension or elevated intraocular pressure, hyperthyroidism, severe hepatic or renal dysfunction.
• History of cerebral infarction, intracerebral hemorrhage, or residual central nervous system deficits.
• Impairments of language, hearing, vision, or cognitive function that would prevent completion of questionnaires or cooperation with sleep monitoring.
• Active oral pathologies.
• Transfer to ICU postoperatively.

Sponsors & Collaborators

• Zhuan Zhang: lead

Study Sites (2)

Jingjiang People's Hospital Affiliated to Yangzhou University, Yangzhou University

Jingjiang, Jiangsu, 214500, China

Location

The Affiliated Hospital of Yangzhou University, Yangzhou University

Yangzhou, Jiangsu, 225012, China

Location

MeSH Terms

Interventions

Esketamine; Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Zhuan Zhang, MD

CONTACT

+86-15062791355; zhangzhuancg@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, the Deputy Director of Anesthesiology, the Affiliated Hospital of Yangzhou University, Yangzhou University

Study Record Dates

• First Submitted: December 4, 2025
• First Posted: January 2, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)