Circadian RhythmNCT07315074
Effect of Esketamine on Postoperative Sleep in Postmenopausal Women
A study testing Esketamine and Normal Saline in people with Circadian Rhythm and Postoperative Sleep Disturbance, run by Zhuan Zhang at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older, women only
- Conditions the study is for
- Circadian Rhythm, Postoperative Sleep Disturbance
- What is being tested?
- Esketamine and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 164 participants
- Where
- 2 sitesChina
- Study dates
- 1 Mar 2026to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Jingjiang People's Hospital Affiliated to Yangzhou University, Yangzhou University
Jingjiang, Jiangsu, 214500
Xiang Pu, Master Degree, +86-18951150271
- Recruiting
The Affiliated Hospital of Yangzhou University, Yangzhou University
Yangzhou, Jiangsu, 225012
Zhuan Zhang, MD, +86-15062791355, zhangzhuancg@163.com
About this study
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.
Read more
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
- Being tested
- Esketamine, Normal Saline
- Keywords
- Esketamine, Circadian Rhythm, Melatonin, Postoperative Sleep Disturbance, Postmenopause
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
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.
Normal SalineDrug
In Group C, 0.9% sodium chloride with a maintenance dose of 0.1 ml·kg-¹·h-¹ are administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Esketamine Group (Group E) | Experimental | Not described Receives: Drug: Esketamine |
| Control Group (Group C) | Placebo comparator | Not described Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Postoperative day 1.
Secondary outcomes (8)
Biological rhythm detection
Melatonin and cortisol rhythm profiles are analyzed using saliva samples every 6 h for 48 h: at 10:00 PM on the night of surgery; 4:00 AM, 10:00 AM, 4:00 PM, and 10:00 PM on postoperative day 1; and 4:00 AM and 10:00 AM on postoperative day 2.
Expression of core circadian clock genes, serum melatonin and cortisol concentrations are assessed on preoperative day 1, postoperative day 1 and postoperative day 3.
Measured: From preoperative day 1 to postoperative day 3.
Objective sleep parameters recorded by actigraphy
Objective sleep parameters are recorded using actigraphy.The parameters include total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), proportion of WASO (WASO%), and sleep efficiency (SE%).
Measured: From preoperative night 1 to postoperative night 3.
Subjective sleep quality
The Pittsburgh Sleep Quality Index (PSQI) is assessed on the day before surgery and 30 days postoperatively. Self-rated sleep quality is evaluated using the NRS and the AIS on the day before surgery and on postoperative days 2 and 3.
Measured: From preoperative day 1 to postoperative day 30.
Anxiety and Depression assessments
Anxiety and depression are measured using the Hospital Anxiety and Depression Scale (HADS). It comprises two subscales: the Anxiety subscale (HADS-A) and the Depression subscale (HADS-D). For each item, respondents select the degree of severity, ranging from 0 to 3, representing none, mild, moderate, and severe. The total score for each subscale ranges from 0 to 21, with higher scores indicating more severe anxiety or depression symptoms. Scores of 0-7 are considered normal, 8-10 suggest the possibility of mild anxiety or depression, 11-14 indicate the possibility of moderate anxiety or depression, and 15-21 signify the possibility of severe anxiety or depression.
Measured: From preoperative day 1 to postoperative day 3.
Frontal electroencephalography
Electroencephalogram (EEG) data is collected using the ConView Anesthesia Depth Monitoring System (ConView YY-105, Zhejiang Puke Medical Technology Co., Ltd., China). The analysis includes the power spectrum of EEG energy across various frequency bands, the peak frequencies in the α-β band, and key electrocorticogram indices such as the left α-index (Aileft), right α-index (Airight), electromyographic index (EMG), and burst suppression ratio (BSR).
Measured: From entering the operating room to surgery ending.
Postoperative cognitive function and biomarkers
Delirium assessments is conducted twice daily on postoperative days 1, 2, and 3 with at least 6 hours interval between evaluations, using the Chinese version of the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM).
Brain-derived neurotrophic factor (BDNF) and S100-β are measured from blood samples collected on preoperative day 1, postoperative day 1 and postoperative day 3.
Measured: From preoperative day 1 to postoperative day 3.
Inflammatory markers
Inflammatory biomarkers including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 are measured.
Measured: From preoperative day 1 to postoperative day 3.
Postoperative pain assessment
Pain levels, including both rest and exercise pain, are measured using the Visual Analogue Scale (VAS) at 24 hours, 48 hours, and 72 hours postoperatively. Data on the use of the Patient-Controlled Analgesia (PCIA) device, including trigger times for bolus doses within the first 24 hours post-surgery, the total number of bolus presses, and the use of the rescue analgesic flurbiprofen, are documented.
Measured: From postoperative day 1 to day 3.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2026
- Study start1 Mar 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Circadian RhythmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhuan Zhang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Zhuan Zhang, Yangzhou University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07315074
- Sponsor's protocol ID
- 20251115
- Status last verified
- Aug 2026
- First submitted
- 4 Dec 2025
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Esketamine on Postoperative Sleep in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT07315074
- Acronym / sponsor ID
- 20251115
- Conditions
- Circadian Rhythm, Postoperative Sleep Disturbance
- Keywords
- Esketamine, Circadian Rhythm, Melatonin, Postoperative Sleep Disturbance, Postmenopause
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Zhuan ZhangUniversity, hospital or other
- Study start
- 1 Mar 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 2 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esketamine Group (Group E) | Experimental | Drug: Esketamine |
| Control Group (Group C) | Placebo comparator | Drug: Normal Saline |
Who may qualify
- Ages
- 45 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsketamineParticipants 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. | Drug | Esketamine Group (Group E) |
| Normal SalineIn Group C, 0.9% sodium chloride with a maintenance dose of 0.1 ml·kg-¹·h-¹ are administered intravenously. | Drug | Control Group (Group C) |
Primary outcome
The incidence of postoperative sleep disturbance (PSD) on postoperative day 1.
Time frame: 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.
8 secondary outcomes
Biological rhythm detection
Time frame: From preoperative day 1 to postoperative day 3.
Objective sleep parameters recorded by actigraphy
Time frame: From preoperative night 1 to postoperative night 3.
Subjective sleep quality
Time frame: From preoperative day 1 to postoperative day 30.
Anxiety and Depression assessments
Time frame: From preoperative day 1 to postoperative day 3.
Frontal electroencephalography
Time frame: From entering the operating room to surgery ending.
Postoperative cognitive function and biomarkers
Time frame: From preoperative day 1 to postoperative day 3.
Inflammatory markers
Time frame: From preoperative day 1 to postoperative day 3.
Postoperative pain assessment
Time frame: From postoperative day 1 to day 3.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Esketamine and Normal Saline in people with Circadian Rhythm and Postoperative Sleep Disturbance, run by Zhuan Zhang at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhuan Zhang, MD (+86-15062791355, zhangzhuancg@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of postoperative sleep disturbance (PSD) on postoperative day 1. (time frame: Postoperative day 1.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.