Low-Frequency rTMS for In-Hospital Sleep Disturbance After Lung Transplantation

NCT07796425 | Not Yet Recruiting Phase 2

• 1 other identifier: TMS-SLEEP-LTx-01
• Study Type: interventional
• Target: 152
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized, double-blind, sham-controlled trial will evaluate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) can improve in-hospital sleep quality in adult lung transplant recipients during early postoperative recovery. A total of 152 participants with in-hospital sleep disturbance after first single- or double-lung transplantation will be randomly assigned in a 1:1 ratio to active rTMS or matched sham stimulation. Active rTMS will target the left dorsolateral prefrontal cortex and will be delivered once daily for 10 sessions within 10-14 days. The primary outcome is sleep quality measured using the Richards-Campbell Sleep Questionnaire during the nights following stimulation sessions 8, 9, and 10. The study will also evaluate wearable-device sleep measures, insomnia symptoms, pain, mood, cognitive and functional outcomes, safety, feasibility, and changes in brain activity measured by 64-channel electroencephalography.

Conditions

Sleep Wake Disorders; Lung Transplantation

Keywords

Repetitive Transcranial Magnetic Stimulation; rTMS; In-Hospital Sleep Disturbance; Lung Transplant Recipients; Dorsolateral Prefrontal Cortex; Richards-Campbell Sleep Questionnaire; 64-Channel Electroencephalography

Outcome Measures

Primary Outcomes (1)

• Mean Richards-Campbell Sleep Questionnaire Total Score Across the Nights Following Stimulation Sessions 8-10

  The Richards-Campbell Sleep Questionnaire (RCSQ) total score is calculated as the mean of five visual analog items and ranges from 0 to 100, with higher scores indicating better sleep. The primary outcome is the participant-level mean RCSQ total score obtained on the mornings after the nights following stimulation sessions 8, 9, and 10. At least two valid RCSQ nights are required to calculate the mean. The primary analysis will adjust for the mean RCSQ score from two consecutive valid baseline inpatient nights.

  Mornings after the nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period

Secondary Outcomes (6)

• Mean Total Sleep Time Measured by Lifesense HR6 Across the Nights Following Stimulation Sessions 8-10

  Nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period

• Generalized Anxiety Disorder-7 Score

  Baseline; 24-72 hours after the final stimulation session

• Patient Health Questionnaire-9 Score

  Baseline; 24-72 hours after the final stimulation session

• EQ-5D-5L Health-Related Quality of Life

  Baseline; 24-72 hours after the final stimulation session

• Proportion of Participants Completing at Least 8 of 10 Stimulation Sessions

  During the 10-14-day treatment period

Other Outcomes (3)

• Change in Prespecified EEG Frequency-Band Power

  Baseline and 2-24 hours after stimulation session 10.

• Change in Prespecified EEG Functional Connectivity

  Baseline and 2-24 hours after stimulation session 10.

• Change in TMS-Evoked Cortical Response

  Baseline and 2-24 hours after stimulation session 10.

Study Arms (2)

Active Low-Frequency rTMS

EXPERIMENTAL

Participants assigned to this arm will receive active low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex at the F3 position. Stimulation will be delivered at 1 Hz and 100% of the resting motor threshold, with 1,800 pulses per session over approximately 30 minutes, once daily for a total of 10 sessions completed within 10-14 days. Participants will continue to receive standard post-transplant care and standardized inpatient sleep-support measures.

Device: Active Low-Frequency Repetitive Transcranial Magnetic Stimulation

Sham rTMS

SHAM COMPARATOR

Participants assigned to this arm will receive matched sham rTMS using a dedicated sham coil or validated active/sham masking module. The sham procedure will match the active treatment in target location, participant positioning, stimulation rhythm, sound, session duration, and study interaction procedures, but will not produce the intended therapeutic cortical stimulation. Participants will receive the same standard post-transplant care and inpatient sleep-support measures as the active rTMS group.

Device: Sham Repetitive Transcranial Magnetic Stimulation

Interventions

Active Low-Frequency Repetitive Transcranial Magnetic Stimulation DEVICE

Active rTMS will be delivered over the left dorsolateral prefrontal cortex at the F3 position using a figure-of-eight coil. Stimulation parameters are 1 Hz, 100% of the resting motor threshold, and 1,800 pulses per session over approximately 30 minutes. Treatment will be administered once daily for a total of 10 sessions completed within 10-14 days during the same hospitalization. No more than one study stimulation session will be administered on the same calendar day.

Active Low-Frequency rTMS

Sham Repetitive Transcranial Magnetic Stimulation DEVICE

Sham stimulation will be administered using a dedicated sham coil or validated active/sham masking module compatible with the locked study device. The target location, participant positioning, stimulation rhythm, sound, session duration, and interaction procedures will match active rTMS, but the sham procedure will not produce the intended therapeutic cortical stimulation. Sham stimulation will be administered once daily for a total of 10 sessions within 10-14 days.

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years and able to provide independent written informed consent. First single- or double-lung transplantation. Postoperative day 7-21 at randomization; extubated for at least 48 hours, off ECMO, and off vasoactive medications for at least 24 hours.
• Resting SpO2 ≥92% with stable oxygen requirements and able to complete study procedures in a seated or semi-recumbent position.
• Negative CAM/CAM-ICU assessment during the preceding 24 hours, with clear consciousness and ability to complete sleep and cognitive assessments.
• Stable trends in blood pressure, blood glucose, serum sodium, serum magnesium, and renal function; immunosuppressant concentrations considered acceptable by the transplant team.
• Mean RCSQ score \<70 across two consecutive valid inpatient nights and baseline ISI score ≥8.
• Able to complete RCSQ, sleep diary, Lifesense HR6 monitoring, and 64-channel EEG assessments.
• Expected to remain hospitalized for at least 10 days and able to complete 10 stimulation sessions and the primary outcome assessment within 14 days.

You may not qualify if:

• Unable to provide valid informed consent, unwilling to participate, or unable to reliably complete the primary RCSQ assessment.
• History of epilepsy or unexplained seizures, active intracranial hemorrhage, significant cerebral edema, elevated intracranial pressure, recent stroke, or severe traumatic brain injury.
• Intracranial ferromagnetic metal, cochlear implant, deep brain stimulator, cardiac pacemaker/implantable cardioverter-defibrillator, or other TMS-incompatible implant.
• Severe scalp infection, open wound, or inability to safely position the TMS coil or EEG cap.
• Pregnancy or any condition considered by the investigator to pose unacceptable risk.
• Repeat lung transplantation, multiorgan transplantation, or current requirement for ECMO, mechanical ventilation, or vasoactive support.
• Active delirium, encephalopathy, posterior reversible encephalopathy syndrome (PRES), central nervous system infection, new focal neurological deficit, or seizure within the previous 30 days.
• Suspected calcineurin-inhibitor neurotoxicity, uncontrolled hypertension, clinically significant hypomagnesemia, hyponatremia, hypoglycemia, or other metabolic abnormality that may lower the seizure threshold.
• Uncontrolled sepsis, active rejection requiring urgent intensified treatment, or rapidly deteriorating clinical status.

Sponsors & Collaborators

• The First Affiliated Hospital of Guangzhou Medical University: lead

MeSH Terms

Conditions

Sleep Wake Disorders

Condition Hierarchy (Ancestors)

Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors will be masked to treatment allocation. The clinical care team, follow-up personnel, and statistical personnel will also remain masked whenever applicable. Because of device-operation requirements, the stimulation operator cannot be masked but will not participate in participant recruitment, primary outcome assessment, data entry, or statistical analysis. Emergency unmasking will be permitted only when knowledge of treatment allocation is necessary for urgent clinical management.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Model Details: Participants will be randomized in a 1:1 ratio to active low-frequency rTMS or matched sham stimulation using a parallel-group design. Both groups will receive standard post-transplant care and the same inpatient sleep-support measures.

Study Record Dates

• First Submitted: August 15, 2026
• First Posted: September 1, 2026
• Study Start: August 31, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: September 1, 2026

Record last verified: 2026-08