Effects of Accelerated rTMS on Sleep Architecture in Chronic Insomnia Disorder

NCT07595185 | Not Yet Recruiting FDA Device

• 1 other identifier: SFNSC-2026-001
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic insomnia disorder is a common condition in which people have ongoing difficulty falling asleep, staying asleep, or waking too early. It affects about 10-12% of adults and can lead to daytime problems, stress, and other health issues. Current treatments include talk therapy (cognitive behavioral therapy for insomnia) and sleep medications, but medications can have side effects and may not work well over the long term. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that uses magnetic pulses applied to the scalp to stimulate specific areas of the brain. It has shown promise in improving sleep quality in people with insomnia by targeting a brain region called the left dorsolateral prefrontal cortex, which plays a role in the overactive brain arousal thought to cause insomnia. The purpose of this study is to find out whether an accelerated course of rTMS using the EXOMIND™ device can improve sleep in adults with chronic insomnia disorder. The study will enroll approximately 70 participants aged 18 to 85 years at a single site in San Francisco. Participants will receive 6 rTMS sessions (3 times per week for 2 weeks). Each session lasts about 25 minutes. The study has three phases: a screening phase (up to 25 days) to confirm eligibility using sleep questionnaires and at-home sleep monitoring, a 2-week open-label treatment phase, and a follow-up phase with visits at 1 month and 3 months after the last treatment session. Total participation lasts up to approximately 139 days. The main goal is to measure whether insomnia severity improves after treatment, using a standard questionnaire called the Insomnia Severity Index (ISI). The study will also measure changes in objective sleep patterns (such as how long it takes to fall asleep, time spent in deep sleep, and total sleep time) recorded by a home sleep monitoring device, as well as changes in sleep quality, stress levels, and overall clinical impression of improvement. This is an open-label pilot study, meaning all participants will receive the rTMS treatment and there is no placebo group. The study does not involve any medications. Participants must not have certain medical conditions, electronic or metal implants in or near the head, untreated sleep apnea, or active serious psychiatric disorders. Participants who are pregnant or breastfeeding cannot take part.

Conditions

Insomnia; Chronic Insomnia; Chronic Insomnia Disorder; Sleep Disturbance

Keywords

Sleep Efficiency; Chronic Insomnia Disorder; Insomnia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Insomnia Severity Index (ISI) Total Score at 1-Month Follow-Up

  The Insomnia Severity Index (ISI) is a 7-item self-report questionnaire that assesses the nature, severity, and impact of insomnia. Each item is rated on a 0-4 Likert scale, yielding a total score ranging from 0 to 28. Higher scores indicate greater insomnia severity. Clinical severity categories are: 0-7 (no clinically significant insomnia), 8-14 (subthreshold insomnia), 15-21 (moderate clinical insomnia), and 22-28 (severe clinical insomnia). The primary outcome is the change in ISI total score from baseline (Day 1, pre-treatment) to the 1-month follow-up visit. A negative change indicates improvement.

  From baseline to the 1-month follow-up

Secondary Outcomes (14)

• Change From Baseline in Sleep Onset Latency (SOL)

  Baseline (night before Day 1), day of last rTMS session (approximately Day 21), 1-month follow-up (approximately Day 51), and 3-month follow-up (approximately Day 111)

• Change From Baseline in Stage N3 Duration

  Baseline (night before Day 1), day of last rTMS session (approximately Day 21), 1-month follow-up (approximately Day 51), and 3-month follow-up (approximately Day 111)

• Change From Baseline in Wake After Sleep Onset (WASO)

  Baseline (night before Day 1), day of last rTMS session (approximately Day 21), 1-month follow-up (approximately Day 51), and 3-month follow-up (approximately Day 111)

• Change From Baseline in Total Sleep Time (TST)

  Baseline (night before Day 1), day of last rTMS session (approximately Day 21), 1-month follow-up (approximately Day 51), and 3-month follow-up (approximately Day 111)

• Change From Baseline in Sleep Efficiency (SE)

  Baseline (night before Day 1), day of last rTMS session (approximately Day 21), 1-month follow-up (approximately Day 51), and 3-month follow-up (approximately Day 111)

Study Arms (1)

rTMS Treatment

EXPERIMENTAL

Participants receive 6 sessions of repetitive transcranial magnetic stimulation (rTMS) using the EXOMIND™ device (BTL-699-2), administered 3 times per week over 2 weeks. Each session delivers 6,300 magnetic pulses at alternating frequencies of 12, 15, and 18 Hz to the left dorsolateral prefrontal cortex (DLPFC), localized using the standard 5.5-cm anterior method. Total session duration is 24 minutes and 30 seconds. Stimulation intensity is calibrated to each participant's individual motor threshold, defined as the minimum stimulus required to produce visible contraction of the right thumb. All sessions are conducted on-site at the research center with medical staff present. Blood pressure and heart rate are monitored before and after each session.

Device: TMS

Interventions

TMS DEVICE

The EXOMIND™ (BTL-699-2) is a repetitive transcranial magnetic stimulation (rTMS) device that delivers targeted electromagnetic pulses to cortical brain regions. In this study, stimulation is applied to the left dorsolateral prefrontal cortex (DLPFC), a region implicated in executive function, working memory, and attention. The DLPFC target is localized using the standard 5-cm rule, measured anterior to the motor cortex hot spot. Each treatment session uses a multi-frequency protocol alternating between 12, 15, and 18 Hz stimulation frequencies, delivering a total of 6,300 pulses over 24 minutes and 30 seconds. Stimulation intensity is calibrated to each participant's resting motor threshold, defined as the minimum stimulus intensity required to produce a visible contraction of the right abductor pollicis brevis muscle. Six sessions are administered twice weekly over approximately 3 weeks.

rTMS Treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be 18 to 85 years of age, inclusive, on the day of signing informed consent.
• Subject must meet DSM-5 criteria for insomnia disorder：
• A predominant complaint of dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms:
• Difficulty initiating sleep Difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings Early-morning awakening with inability to return to sleep. The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning.
• The sleep difficulty occurs at least 3 nights per week. The sleep difficulty is present for at least 3 months. The sleep difficulty occurs despite adequate opportunity for sleep. The insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder (eg, narcolepsy, a breathing-related sleep disorder, a circadian rhythm sleep-wake disorder, a parasomnia).
• The insomnia is not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication).
• Coexisting mental disorders and medical conditions do not adequately explain the predominant complaint of insomnia.
• Subject must have an ISI total score ≥15 at screening.
• Subject must have an sSOL ≥45 minutes and an sWASO ≥60 minutes on at least 3 nights over any 7-day period during Part 1 of screening, using the CSD-M, prior to screening Somfit™ sleep test assessments.
• Subject must demonstrate a 2-night mean SOL of ≥25 minutes (with neither night \<20 minutes), a 2-night mean WASO ≥30 minutes, and a 2-night mean TST ≤6.5 hours, with neither night \>7 hours.
• Subject must be otherwise healthy or present with stable, well-controlled, chronic conditions on the basis of physical examination, medical history, vital signs, 12-lead ECG (if necessary), and clinical laboratory tests (if necessary) performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population. If the results of the clinical laboratory tests are outside the normal reference ranges, the subject may be included only if the investigator and the sponsor's Safety Physician judge the abnormality or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initiated by the investigator.
• Body mass index between 18 and 35 kg/m2 inclusive (body mass index = weight/height\^2).
• For subjects ≥65 years of age, a Mini-Mental State Examination score of ≥25 to rule out cognitive impairment in the interest of subject safety.
• Ability to determine the motor threshold of the participant. The participant's motor threshold could be established as the minimum stimulus required to induce contraction of the right thumb.
• Subjects willing and able to abstain from partaking in any treatments other than the study procedure for the improvement in sleep quality and reduction of stress, including non-invasive brain stimulation treatments other than the study procedure during study participation.

You may not qualify if:

• Note: Subjects with chronic but stable, well-controlled conditions may be allowed in the study upon agreement with the investigator and the sponsor's Safety Physician.
• Has uncontrolled hypertension (supine systolic blood pressure \>150 mm Hg in adult subjects or \>160 mm Hg in elderly subjects or supine diastolic blood pressure \>90 mm Hg, despite diet, exercise, or a stable dose of allowed antihypertensive therapy) at screening or Day 1. (A subject with hypertension may be included if the subject's hypertension has been controlled for at least 3 months prior to screening, and the dosage of any antihypertensive medication has been stable for the past 3 months).
• Has clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening. Subjects with non-insulin dependent diabetes mellitus who are adequately controlled (hemoglobin A1c \[HbA1c\] ≤8%) may be eligible to participate if otherwise medically healthy. It is expected that laboratory values will generally be within the normal range, though minor deviations, which are not considered to be of clinical significance to both the investigator and the sponsor's Safety Physician, are acceptable.
• Has clinically significant ECG abnormalities at screening or Day 1 prior to treatment defined as:
• T interval corrected according to Fridericia's formula: ≥450 msec (males);
• ≥470 msec (females). Evidence of 2nd and 3rd degree atrioventricular block, or 1st degree atrioventricular block with PR interval \>210 msec, left bundle branch block.
• Features of new ischemia. Other clinically important arrhythmia. Note: Subjects with right bundle branch block may be allowed provided confirmation that right bundle branch block is not associated with underlying cardiac/lung diseases.
• Electronic implants in or near the head - rTMS devices are contraindicated for use in patients who have active or inactive implants in or near the head including device leads, deep brain stimulators, cochlear implants, ocular implants, and vagus nerve stimulators, implanted devices such as cardiac pacemakers, defibrillators, and neurostimulators.
• Metallic, ferromagnetic or other magnetic-sensitive implants/objects in or near the head - rTMS devices are contraindicated for use in patients who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head (with some exceptions in the mouth - see Operator's Manual) or within 12 in (30 cm) of the therapy coil. (Examples include implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry, hair barrettes and tattoos with metallic ink), drug pumps (within 12 in (30 cm) of the therapy coil) application in the heart area.
• Has significant hypersomnia not related to night time insomnia (based on clinical judgment of the investigator).
• Moderate-to-severe obstructive sleep apnea (AHI ≥15 events/hour) that is untreated or inadequately controlled (residual AHI ≥5 events/hour on CPAP therapy).
• Regularly naps more than 3 times per week.
• Has a current diagnosis or recent history of psychotic disorder, MDD, bipolar disorder, or posttraumatic stress disorder, or other psychiatric condition that, in the investigator's opinion, would interfere with the subject's ability to participate in the trial.
• Has a current or recent history of serious suicidal ideation within the past 6 months, or a history of suicidal behavior within the past year. Subjects with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan within the past 6 months, should be carefully screened for current suicidal ideation and only subjects with non-serious items may be included at the discretion of the investigator.
• Has insomnia related to RLS (defined as PLM-arousal index of ≥10 PLM-related electroencephalograph (EEG) arousals per hour of sleep for adult subjects or \>15 for elderly subjects), sleep breathing disorder (defined as an apnea-hypopnea index ≥10 cumulative apneas and hypopneas per hour of EEG sleep for adult subjects or \>15 for elderly subjects), or parasomnias. These disorders will be ruled out by the first PSG recording during Part 2 of screening.

Sponsors & Collaborators

• San Francisco Neurology and Sleep Center: lead

Study Sites (1)

San Francisco Neurology and Sleep Center

San Francisco, California, 94110, United States

Location

Related Publications (9)

• Lu Q, Gu H, Jiang Z, Yang Q, Hu W, He C. Reduced coupling between global brain activity and cerebrospinal fluid flow in middle-aged and older adults with chronic insomnia: enhancement by low-frequency rTMS. Sleep. 2026 Feb 4:zsag016. doi: 10.1093/sleep/zsag016. Online ahead of print.

  PMID: 41636601 BACKGROUND

• Sun J, Li P, Yi Y, Xu W, Zhang G, Zhang B, Ding K, Luo S, Zhou J. Effects of mPFC-rTMS in chronic Insomnia: A randomized, double-blind, placebo-controlled study. Sleep Med. 2025 Oct;134:106704. doi: 10.1016/j.sleep.2025.106704. Epub 2025 Jul 29.

  PMID: 40774161 BACKGROUND

• Gong L, Yang X, He Y, Li H, Zhou W, Liu D, Zhang B, Xi C. Precision targeting of right dorsolateral prefrontal cortex with neuronavigated rTMS alleviates chronic insomnia via functional connectivity reorganization: a randomized neuroimaging trial. Neuroimage Clin. 2025;47:103815. doi: 10.1016/j.nicl.2025.103815. Epub 2025 Jun 4.

  PMID: 40483957 BACKGROUND

• Van Someren EJW. Brain mechanisms of insomnia: new perspectives on causes and consequences. Physiol Rev. 2021 Jul 1;101(3):995-1046. doi: 10.1152/physrev.00046.2019. Epub 2020 Aug 13.

  PMID: 32790576 BACKGROUND

• Riemann D, Nissen C, Palagini L, Otte A, Perlis ML, Spiegelhalder K. The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol. 2015 May;14(5):547-58. doi: 10.1016/S1474-4422(15)00021-6. Epub 2015 Apr 12.

  PMID: 25895933 BACKGROUND

• Morin CM, Buysse DJ. Management of Insomnia. N Engl J Med. 2024 Jul 18;391(3):247-258. doi: 10.1056/NEJMcp2305655. No abstract available.

  PMID: 39018534 BACKGROUND

• Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-349. doi: 10.5664/jcsm.6470.

  PMID: 27998379 BACKGROUND

• van Straten A, Weinreich KJ, Fabian B, Reesen J, Grigori S, Luik AI, Harrer M, Lancee J. The Prevalence of Insomnia Disorder in the General Population: A Meta-Analysis. J Sleep Res. 2025 Oct;34(5):e70089. doi: 10.1111/jsr.70089. Epub 2025 May 14.

  PMID: 40369835 BACKGROUND

• Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):125-33. doi: 10.7326/M15-2175. Epub 2016 May 3.

  PMID: 27136449 BACKGROUND

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Parasomnias

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Central Study Contacts

Joy Shihui Meng, MD

CONTACT

4156662536; office@sf-neurology.com

Junyi Sun, MD, PhD

CONTACT

4156662536; office@sf-neurology.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Model Details: Prospective, open-label, single-arm clinical study

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: May 19, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): May 19, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 19, 2026

Record last verified: 2026-05

Locations

US (1)