Clinical trial NCT06773143: Effect of Subanesthetic Dose of Esketamine on Sleep Quality
Official title: Effect of Subanesthetic Dose of Esketamine on Sleep Quality in Patients With Breast Cancer After Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insomnia
Breast Cancer Surgery
Esketamine
Lead sponsor: Nanjing First Hospital, Nanjing Medical University
Sponsor class: OTHER
First posted: 2025-01-14
Enrollment: 184
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to explore whether subanesthetic doses of esketamine can improve the sleep quality of patients undergoing modified radical mastectomy for breast cancer. In this study, 184 people are expected to participate from admission to three days after surgery.

The process requires participants to cooperate with the completion of the digital rating scale, the Athens Insomnia Scale, the Visual Analog Pain Rating Scale, the Hospital Anxiety and Depression Rating Scale, and the collection of venous blood for research indicators (IL-6, TNF-α, cor, BDNF).

If participants agree to participate in this study, the investigators will assign a unique identification number to each participant and create a medical record for participants.

One day before surgery, the investigators will conduct assessments using the Athens Insomnia Scale, the Visual Analog Pain Rating Scale, and the Hospital Anxiety and Depression Scale, and collect approximately 6 mL of venous blood.

One day after surgery, the investigators will repeat the assessments using the Athens Insomnia Scale, the Visual Analog Pain Rating Scale, and the Hospital Anxiety and Depression Scale. Additionally, the investigators will collect another 6 mL of venous blood and monitor the use of analgesics.

The investigators will follow up with participants three days after the surgery. During this follow-up, investigators will assess any sleep disturbances, administer the Hospital Anxiety and Depression Scale, and review the use of analgesics.

Detailed description: In 2020, breast cancer became the most common cancer worldwide. Treatment methods for breast cancer include surgery, chemotherapy, and endocrine therapy, with surgery remaining the primary treatment option. The emergence of neoadjuvant chemotherapy has expanded the indications for breast cancer surgery, providing surgical opportunities for patients with late-stage clinical staging and a strong desire for breast preservation. Neoadjuvant chemotherapy has the effects of reducing tumor size, lowering clinical staging, assessing the tumor's sensitivity to chemotherapy drugs, and inhibiting tumor cell proliferation. However, chemotherapy, while treating the disease, also causes numerous adverse reactions that directly or indirectly lead to sleep disturbances in patients.

Sleep disturbances reduce cognitive function, immune function, and quality of life in breast cancer chemotherapy patients, with an incidence of sleep disturbances during chemotherapy reaching 80%. These patients, when undergoing surgery, are highly prone to postoperative sleep disturbances (Postoperative Sleep Disturbance, PSD) due to factors such as preoperative sleep disturbances, fear and anxiety about surgery, inflammatory responses, and pain. This negatively impacts their recovery process.

PSD refers to changes in sleep structure and quality in the early postoperative period. It is a clinical syndrome characterized by disturbances in the sleep-wake rhythm following surgery, leading to abnormal sleep quality or sleep behavior, usually manifesting as reduced rapid eye movement (REM) sleep, prolonged wakefulness, and fragmented sleep. There is no unified standard for the duration of PSD, as it varies according to disease type, surgical procedure, and individual differences. Generally, it occurs within a short time after surgery, such as 1-3 days postoperatively. PSD significantly affects the postoperative circadian rhythm, pain levels, inflammatory responses, cognitive function, and cardiovascular outcomes, leading to prolonged recovery time. Clinically, both pharmacological and non-pharmacological interventions are used, with pharmacological treatments primarily involving benzodiazepines, which increase sleep duration and reduce sleep latency. Studying short-term sleep disturbances helps identify and reduce postoperative complications, such as delirium, infections, and cardiovascular events, thus accelerating recovery, improving patient safety, and promoting multidisciplinary collaboration. However, there is limited research on the preventive improvement of sleep quality.

Esketamine, a non-competitive N-methyl-D-aspartate receptor (NMDA) antagonist, is the right-handed isomer of ketamine. It shares a similar pharmacological mechanism with ketamine, but its potency is higher. The most important effect of esketamine is its ability to inhibit the NMDA receptor-mediated glutamate entry into the GABA nervous system, causing excitability changes in the cortex and limbic system, ultimately leading to loss of consciousness. Sub-anesthetic doses of esketamine (0.5 mg/kg, 40-minute intravenous infusion) have been shown to produce rapid and sustained antidepressant effects in patients with treatment-resistant major depressive disorder (MDD).

Additionally, intravenous administration of esketamine at 0.2-0.4 mg/kg (single infusion over 40 minutes) has demonstrated rapid and potent antidepressant effects in the treatment of refractory depression. Apart from its antidepressant effects, esketamine has been proven to improve sleep disturbances in patients with MDD and sleep issues, suggesting that esketamine has potential as a treatment for sleep disorders. Some studies indicate that the antidepressant effect of esketamine is related to the neurobiological structure of wakefulness, sleep, and circadian rhythms. Animal studies also suggest that esketamine can modulate the NF-κB signaling pathway and oxidative stress, inhibiting the release of downstream inflammatory factors, thereby reducing surgical-induced inflammatory damage and playing an anti-anxiety, antidepressant role to improve postoperative recovery quality. However, it remains unclear whether continuous low-dose infusion of esketamine during surgery can reduce the incidence of PSD. This study aims to investigate the impact of continuous infusion of esketamine during surgery on postoperative sleep quality in patients undergoing modified radical mastectomy for breast cancer.

Eligibility criteria: Inclusion Criteria:

1. Patients diagnosed with breast cancer by pathology and immunohistochemistry
2. Patients receiving neoadjuvant chemotherapy
3. Age 18 to 65 years old; d) ;
4. ASA grade Ⅰ - Ⅲ
5. BMI 18 to 30 kg/m2

Exclusion Criteria:

* 1: Patients refuse to participate in the study

  2: BMI \> 30 kg/m2

  3: Recent history of drug abuse

  4: Allergy to or contraindications to esketamine

  5: Cognitive dysfunction or inability to communicate

  6: Severe dysfunction of important organs such as liver and kidney function

Primary outcomes:
measure: The incidence of PSD on postoperative day -1
timeFrame: the first day after surgery
Secondary outcomes:
measure: static Visual Analog Scale score on postoperative day -2
timeFrame: on postoperative day -2
measure: dynamic Visual Analog Scale score on postoperative day -2
timeFrame: on postoperative day -2
measure: anxiety and depression score on the day before surgery
timeFrame: the day before surgery
measure: The incidence of PSD on postoperative day -3
timeFrame: he third day after surgery
measure: The incidence of PSD on postoperative day -5
timeFrame: On the fifth day after surgery
measure: The incidence of PSD on postoperative day 7
timeFrame: On the seventh day after surgery
measure: static Visual Analog Scale score on postoperative day -1
timeFrame: on postoperative day -1
measure: dynamic Visual Analog Scale score on postoperative day -1
timeFrame: on postoperative day -1
measure: BDNF on postoperative day -1
timeFrame: on postoperative day -1
measure: TNFα on postoperative day -1
timeFrame: on postoperative day -1
measure: IL-6 on postoperative day -1
timeFrame: on postoperative day -1
Other outcomes:
measure: IL-6 blood on the day before surgery
timeFrame: the day before surgery
measure: TNFα on the day before surgery
timeFrame: the day before surgery
measure: BDNF on the day before surgery
timeFrame: the day before surgery
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: xiaoliang wang
role: STUDY_DIRECTOR
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