EEG-TMS Intervening Against Postoperative Delirium (RECOVER)

EEG-TMS Intervening Against Postoperative Delirium in Elderly Patients: A Randomized Clinical Trial

Postoperative delirium is common in elderly surgical patients and is associated with complications and prolonged hospitalisation. The aim of the RECOVER study is to assess the efficacy of electroencephalo graph (EEG)-transcranial magnetic stimulation (TMS) treatment for the management of postoperative delirium.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium
• Intervention / Treatment: Device: continuous Theta-burst stimulation; Device: Sham

Detailed Description

Postoperative delirium(POD), a syndrome characterized by an acute change in attention, awareness and cognition, is one of the most common postoperative complications among elderly patients. Impaired neuronal network connectivity is likely one of the several neurobiological processes that contribute to POD pathogenesis. Recently, continuous theta burst stimulation (cTBS), a pattern of TMS, was demonstrated to improve cognitive function in patients with mild cognitive impairment.Recent research suggests that cTBS has positive effect on improving the connectivity and reorganization of the brain network.This project team conducted a pilot study in the early stage and innovatively applied cTBS to treat postoperative delirium in elderly patients. The results preliminarily elucidate the safety, and feasibility of TMS in treating postoperative delirium in elderly patients.

In order to confirm the effectiveness of EEG-TMS therapy for POD and observe its impact on long-term prognosis, this project will conduct a prospective randomized controlled study to compare TMS therapy with sham stimulation therapy. The study will observe The duration of postoperative delirium during the 7-day intervention period, as well as severity of delirium, the time to successful discharge (defined as the patient surviving outside the hospital for at least 48 hours after discharge), and the 30-day and 90-day survival times, the number of patients receiving salvage drug treatment, and the number of days each patient received salvage drug treatment, the sensitivity, specificity, and predictive value of EEG. The trial will provide new ideas for the prediction and treatment of postoperative delirium in clinic.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dan Huang, MD; Phone Number: 86-15921108822; Email: huangdan@renji.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Renji hosipical, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥60 years;
2. Scheduled for non-cardiac surgery;
3. Positive assessment for delirium via the CAM-ICU or 3D-CAM after surgery.

Exclusion Criteria:

1. Chronic use of antipsychotic medications;
2. Receipt of antipsychotic drugs prior to enrollment;
3. Permanently incapacitated patients (lacking decision-making capacity);
4. Inability to undergo delirium assessment (e.g., due to language barriers, deafness, blindness, aphasia, or coma);
5. Treatment withdrawal or brain death;
6. Known pregnancy or lactation;
7. Inability to obtain informed consent per national regulations;
8. Patients under compulsory hospitalization (involuntary commitment) by regulatory authorities;
9. Alcohol withdrawal delirium (delirium tremens);
10. Contraindications to transcranial magnetic stimulation (TMS);
11. Acute infectious diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMS group; The TMS group uses effective coils for transcranial magnetic stimulation treatment twice a day, with a treatment mode of continuous theta burst stimulation (cTBS). The stimulation intensity is set at 80% of the minimum exercise threshold.	Device: continuous Theta-burst stimulation; Treatment parameters: each cTBS session consists of 50 Hz triplets of pulses delivered at 5 Hz for 40 s, totaling 600 pulses, and every set simulation includes 3 sessions. Electrodes are attached to designated head regions (right dorsolateral prefrontal cortex).
Sham Comparator: SHAM group; For patients who experience postoperative delirium and are randomly assigned to the sham group, false coil stimulation is used. The auditory and scalp sensations induced by false coil stimulation are similar to those induced by effective coil stimulation, but there is no electromagnetic penetration into the brain or neural activation.	Device: Sham; the treatment mode was with sham coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of postoperative delirium	Trained clinicians (who have received standardized CAM-ICU/3D-CAM training) will assess patients for POD using either the CAM-ICU or 3D-CAM tool twice a day.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of delirium	The severity of delirium is measured using the The Delirium Rating Scale-Revised-98 (DRS-R-98), which has a total score range of 0 to 46, with higher scores indicating greater severity of delirium.	7 days
Time to successful hospital discharge	Defined as discharge from the hospital with survival outside the hospital for ≥48 hours	90 days
Survival at 30 and 90 days	All-cause mortality	90 days
Number of patients receiving rescue medications	e.g., sedatives, antipsychotics, or other adjunctive therapies for delirium/agitation	7 days
Total days of rescue medication use per patient	Calculated as the sum of days each patient received such therapies	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline on EEG	64-channel high-density EEG is used to assess the change of delta, theta, alpha, beta, gamma brainwave activity.	baseline, 7 days
Change from baseline on sleep scales	The change is measured using the Pittsburgh Sleep Quality Index (PSQI), which provides a total score ranging from 0 to 21, with higher scores indicating worse sleep quality.	Baseline, 90days
Change from baseline on stress scales	Stress is assessed using the Stress Appraisal Measure (SAM), which comprises six subscales rated on a 5-point Likert scale (1='not at all' to 5='extremely'). Higher scores on threat, centrality, and uncontrollability subscales indicate greater perceived stress, whereas higher scores on challenge, controllable-by-self, and controllable-by-others reflect lower stress.	Baseline, 90days
Change from baseline on anxiety scales	Anxiety is assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale, a 7-item self-report questionnaire where respondents rate symptom frequency over the past two weeks on a 4-point Likert scale (0="Not at all" to 3="Nearly every day"). The total score ranges from 0 to 21, with higher scores indicating greater anxiety severity.	Baseline, 90days
Change from baseline on pain scales	The Short-form McGill Pain Questionnaire-2 (SF-MPQ-2) assesses pain intensity across 22 items (0-10 scale), with higher scores indicating worse pain.	Baseline, 90days
Change from baseline on depression scales	The Patient Health Questionnaire-9 (PHQ-9) assesses depression severity through 9 items scored 0-3, with total scores ranging 0-27 (higher scores = worse symptoms).	Baseline, 90days
Change from baseline on cognition scales	Cognition is assessed using the Montreal Cognitive Assessment (MoCA), a 30-point screening tool evaluating multiple domains (attention, memory, language, visuospatial skills), with higher scores indicating better cognitive function	Baseline, 90days

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 27, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: July 13, 2025
• First Submitted That Met QC Criteria: August 1, 2025
• First Posted (Actual): August 3, 2025

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: EEG; TMS; postoperative delirium; cTBS
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Emergence Delirium; Delirium
• Other Study ID Numbers: RECOVER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No