Dexmedetomidine-esketamine and tDCS for Prevention of Neurocognitive Complications After Surgery

NCT07576517 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: 2026-121982293644
• Study Type: interventional
• Target: 1,160
• Locations: 1 country
• Sites: 6

Brief Summary

Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery and associated with worse outcomes. In previous studies, perioperative use of dexmedetomidine-esketamine combination improved analgesia and sleep quality after surgery. Perioperative use of transcranial direct current stimulation (tDCS) also improved sleep quality and reduced delirium occurrence early after surgery. This 2×2 factorial trial is designed to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on early postoperative neurocognitive recovery and delirium occurrence in older patients.

Conditions

Older Patients; Surgery; Dexmedetomidine; Esketamine; Transcranial Direct Current Stimulation; Perioperative Neurocognitive Disorders

Keywords

Older patients; Surgery; Dexmedetomidine; Esketamine; Transcranial direct current stimulation; Perioperative neurocognitive disorders

Outcome Measures

Primary Outcomes (1)

• Incidence of delayed neurocognitive recovery (dNCR)

  Cognitive function will be assessed at baseline and at 5 days after surgery (or before hospital discharge) using the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better cognitive function). Delayed neurocognitive decline (dNCR) is defined as: a \|Z\| value of decline in MoCA score ≥1.96. Z value = \[(change from baseline in MoCA score in a surgical patient - mean change from baseline in MoCA score in the non-surgical group)\] / (standard deviation of change from baseline in MoCA score in the non-surgical group).

  At 5 days after surgery or before hospital discharge

Secondary Outcomes (2)

• Incidence of postoperative delirium

  Up to 4 days after surgery

• Incidence of postoperative neurocognitive disorders (pNCD)

  At 30 days after surgery

Other Outcomes (5)

• Early postoperative pain intensity

  Up to 4 days after surgery

• Early postoperative subjective sleep quality

  During the first 4 nights after surgery

• Length of hospital stay (LOS) after surgery

  Up to 30 days after surgery

Study Arms (4)

Dex-Esk + active tDCS

EXPERIMENTAL

Participants will receive dexmedetomidine-esketamine (Dex-Esk) combination and active transcranial direct current stimulation (tDCS).

Drug: Dex-Esk; Device: Active tDCS

Dex-Esk + sham tDCS

EXPERIMENTAL

Participants will receive dexmedetomidine-esketamine (Dex-Esk) combination and sham (placebo) transcranial direct current stimulation (tDCS).

Drug: Dex-Esk; Device: Sham tDCS

Placebo + active tDCS

EXPERIMENTAL

Participants will receive placebo (normal saline) and active transcranial direct current stimulation (tDCS).

Drug: Placebo; Device: Active tDCS

Placebo + sham tDCS

PLACEBO COMPARATOR

Participants will receive placebo (normal saline) and sham (placebo) transcranial direct current stimulation (tDCS).

Drug: Placebo; Device: Sham tDCS

Interventions

Dex-Esk DRUG

Dexmedetomidine-esketamine combination (1 μg/mL dexmedetomidine and 0.5 mg/mL esketamine) will be administered after anesthesia induction, firstly as a loading dose at a rate of \[0.4 x body weight (kg)\] mL/h for 30 minutes (0.2 μg/kg dexmedetomidine and 0.1 mg/kg esketamine), followed by a maintenance infusion at a rate of \[0.1 x body weight (kg)\] mL/h (0.1 μg/kg/h dexmedetomidine and 0.05 mg/kg/h esketamine) until one hour before the expected end of surgery. Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil, 1.25 μg/mL dexmedetomidine, and 0.25 mg/mL esketamine in normal saline), programmed to deliver 2-mL boluses with an 8-minute lockout interval and an 1-mL/h background infusion, and provided for 48 hours (at least 24 hours).

Also known as: Dexmedetomidine-esketamine combination

Dex-Esk + active tDCS; Dex-Esk + sham tDCS

Placebo DRUG

Placebo (normal saline) will be administered after anesthesia induction, firstly as a loading dose at a rate of \[0.4 x body weight (kg)\] mL/h for 30 minutes, followed by a maintenance infusion at a rate of \[0.1 x body weight (kg)\] mL/h until one hour before the expected end of surgery. Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil in normal saline), programmed to deliver 2-mL boluses with an 8-minute lockout interval and an 1-mL/h background infusion, and provided for 48 hours (at least 24 hours).

Also known as: Normal saline

Placebo + active tDCS; Placebo + sham tDCS

Active tDCS DEVICE

Active transcranial direct current stimulation (tDCS) will be administered using a battery-powered stimulator. The anode will be positioned over the left dorsolateral prefrontal cortex (DLPFC, F3) and the cathode over the right supraorbital region (Fp2). The stimulation intensity will be set at 2.0 mA, featuring a 30-second linear ramp-up at the beginning and a 30-second ramp-down at the end of each session. Each participant will receive a total of three 20-minute sessions of active tDCS. The first session will be provided at 40 minutes after extubation in the post-anesthesia care unit. Two other sessions will be provided on postoperative days 1 and 2 (between 10:00 and 12:00 am).

Also known as: Active transcranial direct current stimulation

Dex-Esk + active tDCS; Placebo + active tDCS

Sham tDCS DEVICE

Sham transcranial direct current stimulation (tDCS) will be administered using a battery-powered stimulator. The anode will be positioned over the left dorsolateral prefrontal cortex (DLPFC, F3) and the cathode over the right supraorbital region (Fp2). To ensure blinding, the device will deliver a initial 30-second ramp-up to 2.0 mA followed immediately by a 30-second ramp-down to 0 mA. The device remains "ON" for the remaining 19 minutes with no effective current output, mimicking the peripheral scalp sensation without delivering cortical modulation. Each participant will receive a total of three 20-minute sessions of sham tDCS. The first session will be provided at 40 minutes after extubation in the post-anesthesia care unit. Two other sessions will be provided on postoperative days 1 and 2 (between 10:00 and 12:00 am).

Also known as: Sham transcranial direct current stimulation

Dex-Esk + sham tDCS; Placebo + sham tDCS

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Aged 65 to 90 years;
• Preoperative Mini-Mental State Examination (MMSE) score \< 27 points, indicating possible cognitive impairment ranging from mild to moderate;
• Scheduled to undergo elective non-cardiac, non-neurosurgical surgery under general anesthesia, with an expected surgical duration \> 1 hour;
• Required patient-controlled intravenous analgesia (PCIA) after surgery.

You may not qualify if:

• Preoperative inability to communicate due to coma, severe dementia, end-stage disease, or language impairment;
• History of schizophrenia, epilepsy, Parkinson's disease, brain trauma/surgery, or myasthenia gravis;
• Presence of metal implants in the intracranial or cervical region (such as cochlear implants, aneurysm clips, deep brain stimulation electrodes), or skin damage or severe skin disease on the head;
• Severe cardiac dysfunction (left ventricular ejection fraction \< 30%), comorbid with sick sinus syndrome, severe bradycardia (heart rate \< 50 bpm), or second-degree or higher atrioventricular block, or implantation of a cardiac pacemaker;
• Uncontrolled hyperthyroidism or pheochromocytoma;
• Severe liver dysfunction (Child-Pugh class C), severe renal dysfunction (requiring dialysis), or ASA classification ≥ IV;
• Allergy to dexmedetomidine or esketamine;
• Participation in other clinical studies within the past 3 months;
• Other conditions that are deemed unsuitable for study participation.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Peking University Shenzhen Hospital: collaborator
• The First Affiliated Hospital of Air Force Medicial University: collaborator
• Zhejiang University: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator
• Fujian Medical University Union Hospital: collaborator

Study Sites (6)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 362011, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

Xijing Hospital, Air Force Medical University

Xi'an, Shaanxi, 710032, China

Location

First Affilited Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310006, China

Location

Second Affilited Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

Location

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MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong-Xin Wang, MD, PHD

CONTACT

86 10 83572784; wangdongxin@hotmail.com

Zhen-Zhen Xu, MD

CONTACT

86 10 83572460; zjxvzhenzhen@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 2, 2026
• First Posted: May 8, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)