Use of Transcranial Magnetic Stimulation in the Post-Operative Cognitive Dysfunction in Elderly

NCT06658769 | Recruiting

• 2 other identifiers: 58398022.1.0000.00686.796.500
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Postoperative Cognitive Dysfunction (POCD) is a prevalent condition with significant clinical, social, and financial impacts on patients and healthcare services. The term POCD refers to any signs of new cognitive impairment that exceed the expected time for recovery from the acute effects of surgery and anesthesia. Mild Cognitive Impairment (MCI) is among the main risk factors and is defined as a small cognitive decline from the previous level of performance in one or more cognitive domains, without interfering with daily activities. Considering the aging population linked to an increase in the number of individuals with MCI and a growing demand for surgery, the identification of interventions that can prevent the occurrence of POCD is necessary. Non-invasive brain stimulation (NIBS) techniques such as TMS (Transcranial Magnetic Stimulation) are widely used in research and clinical practice and involve the modulation of excitability and brain activity, potentially improving the individual's cognitive performance. The aim of this study is to assess the efficacy of a Theta Burst rTMS protocol with few sessions in preventing postoperative cognitive dysfunction in elderly individuals with mild neurocognitive disorder. Methodology: This will be a randomized, blinded clinical trial with volunteers aged \> 60 years, candidates for elective surgeries, who will be randomly allocated into 2 groups: the groups will receive real or sham TBS 15 days before surgery. There will be 3 intervention sessions, with a 72-hour interval between them. Outcome measures will be cognitive psychological assessment and Stroop Test cognitive task performance before and after transcranial magnetic stimulation, after surgery and at the 3-month follow-up. There will be a non-surgical control group with cognitive impairment according to the study inclusion criteria and will receive active stimulation.

Conditions

Postoperative Cognitive Dysfunction

Keywords

Transcranial Magnetic Stimulation; Postoperative Cognitive Dysfunction; Theta Burst Stimulation

Outcome Measures

Primary Outcomes (4)

• Changes in Verbal Learning

  Hopkins Verbal Learning Test (HVLT) - This test consists of a list of 12 words. After the examiner reads the list, the patient is asked to repeat as many words as possible in any order. This procedure is repeated two more times, and after 25 minutes, a delayed recall is requested. The score is based on the number of words recalled in the delayed recall.

  1st evaluation: Baseline. 2nd evaluation: 2 days after the application of the active or sham iTBS protocol. 3rd evaluation: 15 days after surgery (surgical groups) or 20 days after the second evaluation (non-surgical group). 4th evaluation: 3 months afte

• Changes in Attention and Executive Function:

  Trail Making Test (A and B) - The test is divided into two parts: the first part (TMT A) involves simple visual search and motor speed, while the second part (TMT B) requires complex visual search due to the alternation of stimuli, thus assessing executive function performance. In part A, the person must connect numbered circles in ascending order. In part B, they must draw lines alternating between numbers in ascending order and letters in alphabetical order. The test evaluates not only selective and alternating attention but also complex visual tracking and motor dexterity (Part A) as well as executive processes (Part B). The time spent and the number of errors made in each part are assessed.

  1st evaluation: Baseline. 2nd evaluation: 2 days after the application of the active or sham iTBS protocol. 3rd evaluation: 15 days after surgery (surgical groups) or 20 days after the second evaluation (non-surgical group). 4th evaluation: 3 months afte

• Changes in Attention and Processing Speed

  Stroop Test - The Stroop test assesses selective attention, the ability to maintain focus on a task, and the inhibition of the tendency to provide impulsive responses, as well as the speed of information processing. In this task, 99 trials are presented on a computer, featuring the words "green," "red," and "blue," displayed in their respective colors (or not). It measures the response time to name the colors of words that are colored in their actual color (congruent trials) or to state the colors of words with different colors (incongruent trials). It also evaluates the number of correct responses in the trials. Data will be synchronized using MATLAB software.

  1st evaluation: Baseline. 2nd evaluation: 2 days after the application of the active or sham iTBS protocol. 3rd evaluation: 15 days after surgery (surgical groups) or 20 days after the second evaluation (non-surgical group). 4th evaluation: 3 months afte

• Changes in Motor Skills

  The Grooved Pegboard Test - This is a manual dexterity test consisting of a board with 25 holes of the same shape (similar to a keyhole) and size, but arranged in a random orientation, along with small pegs that must be placed into the holes following a predetermined order, using only one hand. The raw data corresponds to the time taken to complete the task, measured in seconds. The dominant hand is tested first, followed by the non-dominant hand.

  1st evaluation: Baseline. 2nd evaluation: 2 days after the application of the active or sham iTBS protocol. 3rd evaluation: 15 days after surgery (surgical groups) or 20 days after the second evaluation (non-surgical group). 4th evaluation: 3 months afte

Study Arms (3)

Pre-surgical intervention group (PREG)

ACTIVE COMPARATOR

Participants in the Pre-surgical intervention group (PREG) will undergo active rTMS 15 days before surgery. The protocol will be intermittent theta-burst (iTBS), with 3 pulses applied at 50Hz and modulated at 5Hz for 2s, repeated every 10s for a total of 120s, totaling 300 pulses, with intensity at 80% of the MRL. The stimulated targets will be the left and right posterior parietal cortex (P3 and P4) and the left and right dorsolateral prefrontal cortex (F3 and F4), totaling 1200 pulses per day

Other: Theta Burst Stimulation

Pre-surgical Control Group (PRECG)

SHAM COMPARATOR

Participants in the Pre-surgical Control Group (PRECG) will undergo simulated rTMS with a 90º coil tilt with the lower part facing the scalp 15 days before surgery. The protocol will be intermittent theta-burst (iTBS), with 3 pulses applied at 50Hz and modulated at 5Hz for 2s, repeated every 10s for a total of 120s, totaling 300 pulses, with intensity at 80% of the MRL. The stimulated targets will be the left and right posterior parietal cortex (P3 and P4) and left and right dorsolateral prefrontal cortex (F3 and F4), totaling 1200 pulses per day.

Other: Theta Burst Stimulation Sham

Non-surgical Control Intervention Group (COG)

ACTIVE COMPARATOR

Participants in the Non-Surgical Control Intervention Group (COG) will undergo active rTMS. The protocol will be intermittent theta-burst (iTBS), with 3 pulses applied at 50Hz and modulated at 5Hz for 2s, repeated every 10s for a total of 120s, totaling 300 pulses, with intensity at 80% of the MRL. The stimulated targets will be the left and right posterior parietal cortex (P3 and P4) and the left and right dorsolateral prefrontal cortex (F3 and F4), totaling 1200 pulses per day

Other: Theta Burst Stimulation

Interventions

Theta Burst Stimulation OTHER

Transcranial Magnetic Stimulation (TMS): A non-invasive brain stimulation (NIBS) technique that involves modulating brain excitability and activity, which can increase or decrease depending on the parameters used. Theta Burst Stimulation (TBS) mimics the brain's natural firing patterns more closely and may have greater effects on cognitive performance.

Also known as: Protocol

Non-surgical Control Intervention Group (COG); Pre-surgical intervention group (PREG)

Theta Burst Stimulation Sham OTHER

Theta Burst Stimulation simulated with 90º coil orientation with lower part external to the scalp.

Also known as: Protocol

Pre-surgical Control Group (PRECG)

Eligibility Criteria

• Age: 60 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 60 years old
• Patients scheduled for elective surgeries of moderate or large scale and candidates for general or spinal anesthesia;
• Patients who demonstrate possible or probable cognitive impairment based on pre-operative screening using the 10-CS (10-point cognitive screening) tool; - For Non-surgical Control Intervention Group, only the first and third criteria will be applied.

You may not qualify if:

• Contraindications for the use of Transcranial Magnetic Stimulation (metal implants in the head, history of seizures or epilepsy, brain trauma or surgery, intracranial hypertension, and complications from exposure to magnetic fields);
• Medical diagnosis of Major Neurocognitive Disorder (any form of dementia, regardless of the stage);
• Indication for skull surgery;
• Conditions that interfere with cognitive testing (presence of severe hearing and vision loss, inability to understand Portuguese);
• Ongoing medication adjustments that affect cortical electrical activity (antidepressants, antipsychotics);
• Difficulty attending treatment during the stipulated evaluation and follow-up period, whether due to socioeconomic or clinical reasons;
• Anticipation of surgical scheduling;

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

University of Sao Paulo

São Paulo, São Paulo, 01246903, Brazil

RECRUITING

Related Publications (5)

• Hoy KE, Bailey N, Michael M, Fitzgibbon B, Rogasch NC, Saeki T, Fitzgerald PB. Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls. Cereb Cortex. 2016 Dec;26(12):4563-4573. doi: 10.1093/cercor/bhv193. Epub 2015 Sep 23.

  PMID: 26400923 BACKGROUND

• Chou YH, Ton That V, Sundman M. A systematic review and meta-analysis of rTMS effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2020 Feb;86:1-10. doi: 10.1016/j.neurobiolaging.2019.08.020. Epub 2019 Aug 27.

  PMID: 31783330 BACKGROUND

• Begemann MJ, Brand BA, Curcic-Blake B, Aleman A, Sommer IE. Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis. Psychol Med. 2020 Nov;50(15):2465-2486. doi: 10.1017/S0033291720003670. Epub 2020 Oct 19.

  PMID: 33070785 BACKGROUND

• Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg. 2011 May;112(5):1179-85. doi: 10.1213/ANE.0b013e318215217e. Epub 2011 Apr 7.

  PMID: 21474666 BACKGROUND

• Skvarc DR, Berk M, Byrne LK, Dean OM, Dodd S, Lewis M, Marriott A, Moore EM, Morris G, Page RS, Gray L. Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies. Neurosci Biobehav Rev. 2018 Jan;84:116-133. doi: 10.1016/j.neubiorev.2017.11.011. Epub 2017 Nov 26.

  PMID: 29180259 BACKGROUND

MeSH Terms

Conditions

Postoperative Cognitive Complications

Interventions

Clinical Protocols

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Central Study Contacts

Deise Ferreira, MSc

CONTACT

+55 11 98032-0345; deise.fsilva@hc.fm.usp.br

Clarice Tanaka, PhD

CONTACT

+55 11 2661-6175; cltanaka@usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double-Blind Randomized Clinical Trial, both participants and outcomes assessors will be blinded to active or sham stimulation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Physiotherapy Division

Model Details: After patients are recruited according to the eligibility criteria during the medical screening at the first preoperative outpatient clinic visit or through active search on the waiting list, agree to participate in the protocol, fill out the safety questionnaire for the use of TMS and the transcranial electrostimulation application form, they will be randomized and allocated into two intervention groups different from the surgical group, based on a random table generated by the website www.randomization.com . The person responsible for the randomization stage will not have any other participation in the study. The group allocation will be confidential and the information regarding the patient group will be placed in opaque and numbered envelopes. Each envelope will be opened on the first day of the neuropsychological evaluation. Group 3, non-surgical control with cognitive impairment, will be automatically directed to active stimulation.

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 26, 2024
• Study Start: April 1, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)