Low-Frequency rTMS for In-Hospital Sleep Disturbance in Advanced NSCLC

NCT07796438 | Not Yet Recruiting Phase 2

• 1 other identifier: TMS-SLEEP-NSCLC-01
• Study Type: interventional
• Target: 160
• 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 adults with advanced non-small cell lung cancer (NSCLC) and clinically significant in-hospital sleep disturbance. A total of 160 participants with unresectable stage IIIB-IIIC or stage IV NSCLC, or recurrent NSCLC not suitable for curative local treatment, 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 completed 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 and symptom burden, psychological symptoms, quality of life, safety, feasibility, and changes in brain activity measured by 64-channel electroencephalography.

Conditions

Sleep Wake Disorders; Carcinoma, Non-Small-Cell Lung

Keywords

Repetitive Transcranial Magnetic Stimulation; rTMS; Advanced Non-Small Cell Lung Cancer; In-Hospital Sleep Disturbance; 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 and within 24-72 hours after the final stimulation session

• Patient Health Questionnaire-9 Score

  Baseline; within 24-72 hours after the final stimulation session

• EORTC QLQ-C30 Global Health Status/Quality of Life Score

  Baseline; within 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 clinically indicated anticancer treatment, supportive 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 clinically indicated anticancer treatment, supportive care, and standardized 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. No more than one study stimulation session will be administered on the same calendar day. Study stimulation will not be performed during intravenous anticancer drug infusion, blood transfusion, sedated bronchoscopy, or clinically significant infusion reactions.

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 study device. 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 completed within 10-14 days.

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years and able to understand the study and provide written informed consent.
• Pathologically or cytologically confirmed non-small cell lung cancer (NSCLC), classified according to the IASLC 9th edition TNM system as unresectable stage IIIB-IIIC, stage IVA-IVB, or recurrent disease after curative-intent treatment and considered by a multidisciplinary team to be unsuitable for further curative local therapy.
• Receiving a stable first-line or later-line systemic anticancer treatment regimen, or receiving inpatient symptom/supportive care after anticancer treatment; the treatment plan must be established before randomization, with no planned initiation of new radiotherapy or change in systemic anticancer therapy before assessment of the primary outcome.
• Mean Richards-Campbell Sleep Questionnaire (RCSQ) score \<70 across two consecutive valid inpatient nights and baseline Insomnia Severity Index (ISI) score ≥8.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and estimated life expectancy ≥3 months.
• Hospitalized for anticancer treatment-related observation, symptom control, or supportive care, with an expected remaining hospital stay of at least 10 days from randomization and ability to complete 10 stimulation sessions and the primary outcome assessment within 14 days.
• Able to complete the prespecified RCSQ assessments and brief sleep diary, continuous Lifesense HR6 monitoring, and 64-channel EEG assessment.

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.
• Active or uncontrolled brain metastases, or brain metastases associated with cerebral edema, hemorrhage, focal neurological symptoms, or a need for escalating corticosteroid treatment.
• Untreated or unstable obstructive sleep apnea, or another primary sleep disorder requiring priority specialist management.
• Initiation, discontinuation, or ≥50% dose change of sedative-hypnotic medication within 48 hours before randomization, or a planned initiation/discontinuation of medication expected to substantially affect sleep before assessment of the primary outcome.
• Planned initiation of new whole-brain or local radiotherapy, first use of high-dose corticosteroids, or switching of systemic anticancer therapy before assessment of the primary outcome.
• ECOG performance status ≥3, uncontrolled respiratory failure, delirium, or inability to reliably complete the prespecified sleep assessments.

Sponsors & Collaborators

• The First Affiliated Hospital of Guangzhou Medical University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Sleep Wake Disorders

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

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

Record last verified: 2026-08