Continuous Theta Burst Stimulation (cTBS) and Postoperative Delirium

Effect of Continuous Theta Burst Stimulation (cTBS) on Postoperative Delirium

To investigate the impact of cTBS on the incidence of postoperative delirium and changes of cognitive function in elderly patients after surgery. To explore whether short-term cTBS can reduce the risk of postoperative delirium as a preventive strategy.

Study Overview

• Status: Completed
• Conditions: Postoperative Delirium; Transcranial Magnetic Stimulation, Repetitive
• Intervention / Treatment: Device: Continuous theta burst stimulation (cTBS); Device: Sham stimulation

Detailed Description

Postoperative delirium is the most common postoperative complications among elderly. Nevertheless, there remains no effective medication or intervention been approved in postoperative delirium. Recent research suggests that continuous theta burst stimulation (cTBS) has shown positive effect on improving global cognitive function in multiple mental disorders. However, the effects on cognitive function in postoperative delirium remain uninvestigated.

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Shanghai 10th People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Participants were included if they:

1. were 65 years old or older;
2. had orthopedic surgery under general anesthesia;
3. had normal cognitive function at enrolment [for illiterate, Mini-Mental State Examination (MMSE) ≥ 17; for individuals with 1-6 years of education, MMSE ≥ 20; for individuals with 7 or more years of education, MMSE ≥ 24];
4. were able to complete cognitive assessments and the Confusion Assessment Method (CAM);
5. Chinese Mandarin as their native language;
6. were willing to participate and being competent to provide informed consent.

Patients were excluded if they:

1. had delirium assessed by CAM before surgery;
2. had neurological diseases (e.g., stroke, Parkinson's disease, etc.) according to International Statistical Classification of Diseases and Related Health Problems 11th Revision (ICD-11);
3. had mental disorders (e.g., major depressive disorder, dementia, etc.) according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5);
4. had contraindications of cTBS (e.g., head trauma, history of epilepsy or metal implants in the head);
5. participating in other clinical studies at the time of screening;
6. having postoperative complications such as pulmonary infection, pulmonary embolism and stroke.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cTBS group; Patients randomly assigned to cTBS group received 9 sessions cTBS for total three days after surgery.	Device: Continuous theta burst stimulation (cTBS); Our active treatment consisted of 600 pulses per session, delivered over the right dorsolateral prefrontal cortex at 80% of resting motor threshold (RMT). Every session cTBS consists of 50 Hz triplets of pulses delivered at 5 Hz for 40 seconds for a total of 600 pulses. Every set simulation includes 3 sessions. All enrolled patient in the cTBS group received 1 set simulation per day with an intersession interval (ISI) of over 30 minutes during the hospitalization after the surgery. The first set of stimulation was given at 4 hours after the end of surgery on the day of surgery. The other sets of stimulation were given at 8 am, 8:30 am and 9:00 am on postoperative day 1and 2, respectively.
Sham Comparator: sham group; Patients randomly assigned to sham group received 9 sessions sham stimulation for total three days after surgery.	Device: Sham stimulation; The sham stimulation group received a sham cTBS (600 pulses per session, 3 sessions per day, ISI ≥ 30mins, 3 days) with the coil set at 90 against the skull. The first set of stimulation was given at 4 hours after the end of surgery on the day of surgery. The other sets of stimulation were given at 8 am, 8:30 am and 9:00 am on postoperative day 1 and 2, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative delirium	Incidence of postoperative delirium on postoperative day 1, 2 and 3 was defined according to the confusion assessment methods (CAM).	3 days after surgery
Cognitive function related to delirium	The cognitive function related to delirium was assessed by using Delirium Symptom Interview Daily (DSI Daily).	3 days after surgery
Severity of postoperative delirium	Severity of postoperative delirium on postoperative day 1, 2 and 3 was defined according to he Confusion Assessment Method based delirium severity evaluation tool (CAM-S).The sum score of CAM-S ranges from 0 (no) to 19 (most severe).	3 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complication and mortality	Rate of complication and mortality during the stay in hospital or up to 7 days after anesthesia/surgery, depending which one is longer	up to 7 days after anesthesia/surgery
Pain level	This was assessed by using Visual Analogue Scale (VAS). The patients scored according to the severity of their pain from no pain (0) to most painful (10).	3 days after surgery
Sleep quality	leep Quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) at baseline (T0), and DSI Daily after surgery.The global PSQI score ranges from 0 to 21, where lower scores denote a healthier sleep quality.	3 days after surgery
Ability of daily living	This was assessed by using Chinese version of Activity of Daily Living (ADL) Scale.The total score of ADLs ranges from 14 to 56 points and higher ADLs scores indicate lower activities of daily living.	up to 7 days after anesthesia/surgery

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Yuan Shen, MD, PhD, Shanghai, Shanghai, China, 200072

Publications and helpful links

General Publications

• Wei X, Wang M, Ma X, Tang T, Shi J, Zhao D, Yuan T, Xie Z, Shen Y. Treatment of postoperative delirium with continuous theta burst stimulation: study protocol for a randomised controlled trial. BMJ Open. 2021 Aug 16;11(8):e048093. doi: 10.1136/bmjopen-2020-048093.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): December 2, 2024
• Study Completion (Actual): December 13, 2024

Study Registration Dates

• First Submitted: November 26, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: postoperative delirium; continuous theta burst stimulation
• 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: dsyy005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No