Prefrontal Theta Burst Stimulation to Improve Cognitive Impairment After ICU Delirium

NCT07452939 | Recruiting DMC FDA Device

• 1 other identifier: IRB202501241
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Many older adults who survive a stay in the intensive care unit (ICU) experience delirium, a sudden change in attention and awareness caused by serious illness. Although delirium may resolve before hospital discharge, many survivors continue to experience ongoing problems with memory, attention, processing speed, and executive function (such as planning, organizing, and multitasking). These cognitive difficulties can interfere with daily activities and may increase long-term risk for cognitive decline. Currently, there are no proven treatments specifically designed to improve thinking and attention after ICU delirium. This study is testing whether a noninvasive form of brain stimulation called intermittent theta burst stimulation (iTBS) is safe, feasible, and potentially helpful for improving cognitive function in older ICU survivors who previously experienced delirium. iTBS is a patterned form of transcranial magnetic stimulation (TMS). It involves placing a magnetic coil gently against the scalp to deliver brief pulses of magnetic energy to a targeted region of the brain. In this study, stimulation is directed at the left dorsolateral prefrontal cortex, an area involved in attention, executive function, and cognitive control. The device used in this study is cleared by the U.S. Food and Drug Administration (FDA) for other conditions (such as depression), but its use for post-delirium cognitive impairment is investigational. This is a randomized, double-blind, sham-controlled pilot trial. Up to 40 community-dwelling adults between the ages of 50 and 75 who are approximately three months after an ICU stay with documented delirium will participate. Individuals with known dementia or certain neurological or psychiatric conditions are excluded to ensure safety and interpretability of results. Participation lasts approximately six weeks and includes 11 total visits: a baseline visit, 10 stimulation sessions over two weeks (five sessions per week), and a one-month follow-up visit. Each stimulation session lasts about 15-20 minutes. Cognitive testing is performed at baseline, immediately after the two-week stimulation period, and again one month later. The primary outcome measure is change in executive function, assessed using the Trail Making Test Part B. Additional tests measure attention, processing speed, language, and memory. The primary goals of this pilot study are to evaluate feasibility (ability to recruit and retain participants), safety, and tolerability of the stimulation protocol, and to estimate the magnitude of any cognitive changes. This study is not designed to establish definitive clinical effectiveness but to generate data to inform larger future trials. The broader goal of this research is to explore whether prefrontal neuromodulation could become a future strategy to promote cognitive recovery after ICU delirium.

Conditions

Post-delirium Cognitive Impairment

Keywords

delirium; dementia

Outcome Measures

Primary Outcomes (1)

• Trails Making Test B

  Time (in seconds) required to complete Part B. Lower scores indicate better executive functioning. There is no fixed maximum score; the test is typically discontinued at 300 seconds. Range 0-300 seconds.

  From enrollment to one-month after the final TMS session

Secondary Outcomes (9)

• Trails Making Test A

  From enrollment to one-month after final TMS session

• Psychomotor Vigilance Task

  From enrollment to one-month after final TMS session

• Digit Symbol Coding

  From enrollment to one-month after final TMS session

• Controlled Oral Word Association Test

  From enrollment to one-month after final TMS session

• Semantic Verbal Fluency Test

  From enrollment to one-month after final TMS session

Study Arms (2)

Intermittent theta burst stimulation

ACTIVE COMPARATOR

Device: Intermittent theta burst stimulation

Sham

SHAM COMPARATOR

Device: Sham

Interventions

Intermittent theta burst stimulation DEVICE

Intermittent theta burst stimulation (iTBS) will be delivered using an FDA-cleared Brain Ultimate M-Series transcranial magnetic stimulation system. Stimulation will target the left dorsolateral prefrontal cortex (DLPFC), localized using the Beam F3 scalp-based method. Each session consists of 600 magnetic pulses delivered over approximately 3 minutes using a standard intermittent theta burst pattern (bursts of 3 pulses at 50 Hz, repeated at 5 Hz), administered at 120% of the participant's resting motor threshold. Resting motor threshold will be determined by visual confirmation of motor-evoked movement in the right abductor pollicis brevis muscle.

Intermittent theta burst stimulation

Sham DEVICE

Sham stimulation will be delivered using the same Brain Ultimate M-Series transcranial magnetic stimulation system and figure-of-eight coil used in the active arm. The coil will be positioned at approximately a 45-degree angle relative to the scalp over the left dorsolateral prefrontal cortex (localized using the Beam F3 method) to minimize effective cortical stimulation while preserving auditory and tactile characteristics of active treatment.

Sham

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible individuals must have experienced an ICU admission with documented delirium (confirmed via documented Confusion Assessment Method for the ICU score12 \[CAM-ICU\] or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition13(p5) \[DSM-5\] criteria)
• Age 50 to 75 years old
• months post-ICU discharge at time of enrollment (defined as within 90 ± 14 days)
• English fluency
• Family or close friend for collateral
• Community-dwelling status
• Montreal Cognitive Assessment14 score between 18 and 25.

You may not qualify if:

• Diagnosis of mild cognitive impairment or dementia (prior to delirium episode)
• Seizure disorder
• Other significant neurologic disease (e.g., Parkinson's, Huntington's, Normal pressure hydrocephalus, tumor, progressive supranuclear palsy, multiple sclerosis, hematomas, traumatic or anoxic brain injury)
• Structural CT/MRI with evidence of infection or other clinically significant focal lesions (cortical strokes not large enough to distort anatomy and/or multiple lacunar infarctions ≤ 1.5cm and/or extensive white matter disease are allowed)
• Unstable or decompensated cardiac disease (e.g., \<3 months myocardial infarction, unstable angina, decompensated congestive heart failure NYHA class 3-4)
• Pacemaker
• Cochlear implants
• Implanted medication pumps
• Intracranial metal implants
• Previous TMS treatment
• Pregnancy (negative urine or serum b-HCG or history of prior surgical sterilization or post-menopausal status \[12 months or more of amenorrhea\])
• Current depressive disorder (Beck Depression Inventory score15 \<13)
• History of suicide attempts
• Schizophrenia
• Bipolar disorder

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida Shands Hospital

Gainesville, Florida, 32610, United States

RECRUITING

Related Publications (5)

• Fuseya K, Mimura Y, Nakajima S, Mimura M, Kasanuki K, Noda Y. A systematic review and meta-analysis on the characteristics of transcranial magnetic stimulation treatment protocols for patients with Alzheimer's disease. J Alzheimers Dis. 2025 May;105(1):28-43. doi: 10.1177/13872877251325887. Epub 2025 Mar 20.

  PMID: 40112319 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

• Pabst A, Proksch S, Mede B, Comstock DC, Ross JM, Balasubramaniam R. A systematic review and meta-analysis of the efficacy of intermittent theta burst stimulation (iTBS) on cognitive enhancement. Neurosci Biobehav Rev. 2022 Apr;135:104587. doi: 10.1016/j.neubiorev.2022.104587. Epub 2022 Feb 22.

  PMID: 35202646 BACKGROUND

• Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.

  PMID: 24088092 BACKGROUND

• Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010 Jul;38(7):1513-20. doi: 10.1097/CCM.0b013e3181e47be1.

  PMID: 20473145 BACKGROUND

MeSH Terms

Conditions

Delirium; Dementia

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases

Central Study Contacts

Shixie Jiang, MD

CONTACT

352-273-5391; delirium-lab@ufl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: March 5, 2026
• Study Start: February 13, 2026
• Primary Completion (Estimated): March 21, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)