InsomniaTREATNCT06656533
Optimizing the Timing of rTMS to Enhance the Administration of Insomnia Treatment
A study testing Repeated Transcranial magnetic stimulation (rTMS) in people with Insomnia, run by Stanford University at 1 site in United States.
Trial summary
Repetitive transcranial magnetic stimulation (rTMS) has shown to be a promising technique for improving insomnia symptoms and sleep quality. However, the impact of circadian rhythmicity on rTMS sessions and its potential influence on insomnia therapy remains unclear. Read more about this study
- Who is it for?
- Ages 25 to 45 years
- Conditions the study is for
- Insomnia
- What is being tested?
- Repeated Transcranial magnetic stimulation (rTMS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2025to 30 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males and females of any racial or ethnic group, aged 25-45 (inclusive)
- Insomnia diagnosis via the DUKE
- Fluent and literate in English
- Written, informed consent
- Reside within 60 miles of Stanford University
Who cannot join
- Presence of other sleep or circadian rhythm disorders that significantly contribute to their sleep disturbance. The presence of these disorders will be assessed by the DUKE structured interview for sleep disorders.
- No regular use of benzodiazepine, opiate, thyroid, anticonvulsant or antipsychotic medications
- Use of psychotropic medications that would significantly impact sleep, alertness, and no illicit drugs.
- Excessive alcohol consumption (\>14 drinks per week or \> 4 drinks per occasion)
- Presence of suicidal ideations representing elevated risk as determined by the Beck Depression Inventory (score of \> 0 on BDI question #9).
- History of neurological or cardiovascular disorders, brain surgery, electroconvulsive or radiation treatment, brain hemorrhage or tumor, stroke, seizures or epilepsy, diabetes, hypo- or hyperthyroidism, head trauma with loss of consciousness greater than thirty minutes.
Show all 16Show fewer
- Substance abuse or dependence
- History of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities OR traumatic brain injury in the past two months
- Severe impediment to vision, hearing and/or hand movement, likely to interfere with the ability to complete the assessments, or are unable and/or unlikely to follow the study protocols
- Pregnant or breast feeding
- Current or lifetime history of bipolar disorder, PTSD or psychosis or current depression
- Received cognitive behavioral therapy for insomnia within the past year
- Current exposure to trauma, or exposure to trauma within the past 3 months
- Working a rotating shift that overlaps with 2400h
- Individuals who were high risk for sleep apnea on the Berlin Questionnaire and are not CPAP adherent
- Participants with a current psychiatric disorder who are also on medications that significantly increase the risk of seizure. The antidepressants clomipramine, bupropion, maprotiline will be excluded because they are known to increase risk of up to 0.5-2.2% from a population reference range of 0.07- 0.08% in the general population and 0.1-4% in the population of people taking antidepressants.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Andrea Goldstein Piekarski, PhD contact
United States1 site, 1 recruiting
- Recruiting
1070 Arastradero Road
Palo Alto, California, 94304
Maryam Ahmadi, PhD, 951-231-3891, ahmadi1@stanford.edu
Andrea Goldstein Piekarski, PhD
About this study
Official title: Improving Insomnia Treatment by Optimizing Timing of rTMS Administration
Repetitive transcranial magnetic stimulation (rTMS) has shown to be a promising technique for improving insomnia symptoms and sleep quality. However, the impact of circadian rhythmicity on rTMS sessions and its potential influence on insomnia therapy remains unclear. Moreover, the effect of rTMS on objective sleep parameters is not fully established. The objective of this pilot study is to establish key feasibility and preliminary data that would be used for an R-level grant application focused on optimizing rTMS therapy for insomnia. The investigators will acquire feasibility data from ten adults with Insomnia disorder. Participants will receive ten sessions rTMS over two weeks, either in the morning or evening. Sleep parameters will be assessed before, during, and after completion of rTMS and brain cortical excitability will be collected before rTMS treatment. The investigators aim to 1) evaluate the impact of circadian timing of rTMS sessions on subjective and objective sleep outcomes, 2) assess the time course of improvements in sleep outcomes, and 3) examine the association between sleep outcomes and cortical excitability. The overarching goal of this work is to optimize rTMS therapy for insomnia by investigating the impact of circadian timing on rTMS sessions and assessing potential variations in subjective and objective measures of sleep.
Read the detailed description
Low frequency (1 Hz) rTMS has shown promise to reduce cortical hyperexcitability and to improve subjective measures of sleep quality and insomnia symptoms in patients with insomnia disorder (ID) (Nardone et al. 2020). However, the few studies to date that have examined the objective measures of sleep parameters using Polysomnography (PSG), have yielded heterogeneous results. The variability in the PSG measures of sleep may potentially be attributed to the effectiveness of rTMS therapy delivered at different times of day because of changes in cortical excitability related across the 24-hour period (Ly et al. 2016) as well as the temporal proximity of the stimulation to sleep. However, the impact of the timing of rTMS administration on improving insomnia has not yet been examined. In this pilot study, the investigators aim to demonstrate the feasibility of the data acquisition using the proposed protocol and to establish preliminary data that would be used in a future R-level grant. Building on this preliminary data, the future R-level grant would be focused on optimizing rTMS therapy for insomnia and sleep quality by manipulating the time of day that the rTMS sessions are delivered. In the following, the investigators will provide their aims for this pilot study.
The investigators' objectives are 1. To assess the impact of morning versus evening administration of rTMS on a) subjective and b) objective sleep outcomes. Here the investigators propose to enroll 10 participants and randomize each to either receive 10 sessions of rTMS over two weeks in the morning or in the evening. This pilot study would provide preliminary time-of-day effects on subjective (sleep diary parameters and insomnia severity) and objective sleep (wristwatch actigraphy and PSG) measures. It characterizes the time course of improvement across the two-week treatment period for a) subjective and b) objective sleep measures. Throughout the multi-week intervention, the investigators will collect subjective and objective sleep measures to characterize the improvement across the two-week period.
Finally, this pilot study would determine whether cortical excitability predicts treatment outcomes. Participants will undergo a TMS-EEG session before rTMS therapy. Cortical excitability will be assessed by measuring TMS-evoked EEG potentials (TEP).
- Conditions
- Insomnia
- Being tested
- Repeated Transcranial magnetic stimulation (rTMS)
- Keywords
- Sleep, Insomnia, rTMS Therapy
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repeated Transcranial magnetic stimulation (rTMS)Other
Transcranial Magnetic Stimulation (TMS) involves a procedure where parts of the participants brain will be non-invasively (i.e. indirectly) stimulated by magnetic pulses. These magnetic pulses induce very brief activity in brain areas underlying the TMS coil. TMS will be performed by giving repetitive pulses (rTMS). rTMS has shown promise to reduce cortical hyperexcitability and to improve subjective measures of sleep quality and insomnia symptoms in patients with insomnia disorder. The goal of this study is to optimize the impact of rTMS therapy on sleep outcomes for patients with insomnia disorder.
| Study group | Role | What they receive |
|---|---|---|
| MORNING GROUP | Experimental | Five participants (21 to 45 years old) experiencing clinically meaningful insomnia symptoms will be enrolled and will receive 10 sessions of right dorsolateral prefrontal cortex (DLPFC) rTMS therapy in the morning over two consecutive weeks. Receives: Other: Repeated Transcranial magnetic stimulation (rTMS) |
| EVENING GROUP | Experimental | Five participants (21 to 45 years old) experiencing clinically meaningful insomnia symptoms will be enrolled and will receive 10 sessions of right dorsolateral prefrontal cortex (DLPFC) rTMS therapy in the evening over two consecutive weeks. Receives: Other: Repeated Transcranial magnetic stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insomnia Severity Index (ISI)
Improvement in insomnia symptoms will be assessed using the Insomnia Severity Index (ISI). ISI is a 7-item self-report questionnaire designed to assess the severity of insomnia symptoms and their impact on daily functioning. Each question is scored on a 5-point Likert scale, with ratings from 0 (no problem) to 4 (very severe problem).
Measured: Insomnia severity index will be collected within one week before and within one week after the 10 sessions (over two weeks) of rTMS therapy.
Pittsburgh Sleep Quality Index
Improvement in subjective sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI is a widely used questionnaire that assesses sleep quality and disturbances over one month. It includes seven components and ranges from 0 to 21, with higher scores indicating poorer sleep quality. A score above 5 is generally considered indicative of poor sleep quality.
Measured: Pittsburgh Sleep Quality Index will be collected within one week before and within one week after the 10 sessions (over two weeks) of rTMS therapy.
Secondary outcomes (2)
OBJECTIVE SLEEP MEASURES
Changes in sleep parameters, objectively measured using an Electroencephalogram (EEG) and Actiwatch, will be assessed following rTMS therapy. Sleep Efficiency (the percentage of time a person spends asleep compared to the total amount of time they spend in bed), Wake After Sleep Onset (the amount of time a person is awake after falling asleep but before waking up for the day), and Sleep Latency ( the amount of time it takes to fall asleep after turning off the lights) will be calculated from EEG and Actiwatches. Additionally, sleep architecture including time spent in sleep stages and spectral measures will be collected using EEG.
Measured: EEG sleep parameters will be collected within one week before and within one week after 10 sessions (over two weeks)of rTMS therapy. Actiwatch sleep measures will be collected from one week before the baseline session to the end of the treatment session.
Cortical Excitability
Cortical excitability, defined as the strength of cortical neural responses to stimulations, will be assessed by measuring TMS-evoked EEG potentials (TEP).
Specifically, the amplitude of the change in EEG data after a single TMS pulse in the supplementary motor area will be quantified and associated with changes in sleep measures and insomnia severity index.
Measured: Cortical excitability will be measured during the first therapy session, before the first rTMS therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2024
- Study start1 Mar 2025
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InsomniaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Goldstein-Piekarski, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06656533
- Sponsor's protocol ID
- 76766
- Acronym
- TREAT
- Status last verified
- Apr 2026
- First submitted
- 11 Oct 2024
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Ly JQM, Gaggioni G, Chellappa SL, Papachilleos S, Brzozowski A, Borsu C, Rosanova M, Sarasso S, Middleton B, Luxen A, Archer SN, Phillips C, Dijk DJ, Maquet P, Massimini M, Vandewalle G. Circadian regulation of human cortical excitability. Nat Commun. 2016 Jun 24;7:11828. doi: 10.1038/ncomms11828.
PubMed 27339884Nardone R, Sebastianelli L, Versace V, Brigo F, Golaszewski S, Pucks-Faes E, Saltuari L, Trinka E. Effects of repetitive transcranial magnetic stimulation in subjects with sleep disorders. Sleep Med. 2020 Jul;71:113-121. doi: 10.1016/j.sleep.2020.01.028. Epub 2020 Feb 19.
PubMed 32173186
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Insomnia Treatment by Optimizing Timing of rTMS Administration
- ClinicalTrials.gov ID
- NCT06656533
- Acronym / sponsor ID
- TREAT / 76766
- Conditions
- Insomnia
- Keywords
- Sleep, Insomnia, rTMS Therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 24 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Repetitive transcranial magnetic stimulation (rTMS) has shown to be a promising technique for improving insomnia symptoms and sleep quality. However, the impact of circadian rhythmicity on rTMS sessions and its potential influence on insomnia therapy remains unclear. Moreover, the effect of rTMS on objective sleep parameters is not fully established. The objective of this pilot study is to establish key feasibility and preliminary data that would be used for an R-level grant application focused on optimizing rTMS therapy for insomnia. The investigators will acquire feasibility data from ten adults with Insomnia disorder. Participants will receive ten sessions rTMS over two weeks, either in the morning or evening. Sleep parameters will be assessed before, during, and after completion of rTMS and brain cortical excitability will be collected before rTMS treatment. The investigators aim to 1) evaluate the impact of circadian timing of rTMS sessions on subjective and objective sleep outcomes, 2) assess the time course of improvements in sleep outcomes, and 3) examine the association between sleep outcomes and cortical excitability. The overarching goal of this work is to optimize rTMS therapy for insomnia by investigating the impact of circadian timing on rTMS sessions and assessing potential variations in subjective and objective measures of sleep.
Detailed description
Low frequency (1 Hz) rTMS has shown promise to reduce cortical hyperexcitability and to improve subjective measures of sleep quality and insomnia symptoms in patients with insomnia disorder (ID) (Nardone et al. 2020). However, the few studies to date that have examined the objective measures of sleep parameters using Polysomnography (PSG), have yielded heterogeneous results. The variability in the PSG measures of sleep may potentially be attributed to the effectiveness of rTMS therapy delivered at different times of day because of changes in cortical excitability related across the 24-hour period (Ly et al. 2016) as well as the temporal proximity of the stimulation to sleep. However, the impact of the timing of rTMS administration on improving insomnia has not yet been examined. In this pilot study, the investigators aim to demonstrate the feasibility of the data acquisition using the proposed protocol and to establish preliminary data that would be used in a future R-level grant. Building on this preliminary data, the future R-level grant would be focused on optimizing rTMS therapy for insomnia and sleep quality by manipulating the time of day that the rTMS sessions are delivered. In the following, the investigators will provide their aims for this pilot study.
The investigators' objectives are 1. To assess the impact of morning versus evening administration of rTMS on a) subjective and b) objective sleep outcomes. Here the investigators propose to enroll 10 participants and randomize each to either receive 10 sessions of rTMS over two weeks in the morning or in the evening. This pilot study would provide preliminary time-of-day effects on subjective (sleep diary parameters and insomnia severity) and objective sleep (wristwatch actigraphy and PSG) measures. It characterizes the time course of improvement across the two-week treatment period for a) subjective and b) objective sleep measures. Throughout the multi-week intervention, the investigators will collect subjective and objective sleep measures to characterize the improvement across the two-week period.
Finally, this pilot study would determine whether cortical excitability predicts treatment outcomes. Participants will undergo a TMS-EEG session before rTMS therapy. Cortical excitability will be assessed by measuring TMS-evoked EEG potentials (TEP).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MORNING GROUP | Experimental | Other: Repeated Transcranial magnetic stimulation (rTMS)Five participants (21 to 45 years old) experiencing clinically meaningful insomnia symptoms will be enrolled and will receive 10 sessions of right dorsolateral prefrontal cortex (DLPFC) rTMS therapy in the morning over two consecutive weeks. |
| EVENING GROUP | Experimental | Other: Repeated Transcranial magnetic stimulation (rTMS)Five participants (21 to 45 years old) experiencing clinically meaningful insomnia symptoms will be enrolled and will receive 10 sessions of right dorsolateral prefrontal cortex (DLPFC) rTMS therapy in the evening over two consecutive weeks. |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Males and females of any racial or ethnic group, aged 25-45 (inclusive)
- Insomnia diagnosis via the DUKE
- Fluent and literate in English
- Written, informed consent
- Reside within 60 miles of Stanford University
Key exclusion criteria (16 listed)
- Presence of other sleep or circadian rhythm disorders that significantly contribute to their sleep disturbance. The presence of these disorders will be assessed by the DUKE structured interview for sleep disorders.
- No regular use of benzodiazepine, opiate, thyroid, anticonvulsant or antipsychotic medications
- Use of psychotropic medications that would significantly impact sleep, alertness, and no illicit drugs.
- Excessive alcohol consumption (\>14 drinks per week or \> 4 drinks per occasion)
- Presence of suicidal ideations representing elevated risk as determined by the Beck Depression Inventory (score of \> 0 on BDI question #9).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repeated Transcranial magnetic stimulation (rTMS)Transcranial Magnetic Stimulation (TMS) involves a procedure where parts of the participants brain will be non-invasively (i.e. indirectly) stimulated by magnetic pulses. These magnetic pulses induce very brief activity in brain areas underlying the TMS coil. TMS will be performed by giving repetitive pulses (rTMS). rTMS has shown promise to reduce cortical hyperexcitability and to improve subjective measures of sleep quality and insomnia symptoms in patients with insomnia disorder. The goal of this study is to optimize the impact of rTMS therapy on sleep outcomes for patients with insomnia disorder. | Other | EVENING GROUP, MORNING GROUP |
Primary outcome
Insomnia Severity Index (ISI)
Time frame: Insomnia severity index will be collected within one week before and within one week after the 10 sessions (over two weeks) of rTMS therapy.
Improvement in insomnia symptoms will be assessed using the Insomnia Severity Index (ISI). ISI is a 7-item self-report questionnaire designed to assess the severity of insomnia symptoms and their impact on daily functioning. Each question is scored on a 5-point Likert scale, with ratings from 0 (no problem) to 4 (very severe problem).
Pittsburgh Sleep Quality Index
Time frame: Pittsburgh Sleep Quality Index will be collected within one week before and within one week after the 10 sessions (over two weeks) of rTMS therapy.
Improvement in subjective sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI is a widely used questionnaire that assesses sleep quality and disturbances over one month. It includes seven components and ranges from 0 to 21, with higher scores indicating poorer sleep quality. A score above 5 is generally considered indicative of poor sleep quality.
2 secondary outcomes
OBJECTIVE SLEEP MEASURES
Time frame: EEG sleep parameters will be collected within one week before and within one week after 10 sessions (over two weeks)of rTMS therapy. Actiwatch sleep measures will be collected from one week before the baseline session to the end of the treatment session.
Cortical Excitability
Time frame: Cortical excitability will be measured during the first therapy session, before the first rTMS therapy.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Results publication: PubMed 27339884Ly JQM, Gaggioni G, Chellappa SL, Papachilleos S, Brzozowski A, Borsu C, Rosanova M, Sarasso S, Middleton B, Luxen A, Archer SN, Phillips C, Dijk DJ, Maquet P, Massimini M, Vandewalle G. Circadian regulation of human cortical excitability. Nat Commun. 2016 Jun 24;7:11828. doi: 10.1038/ncomms11828.
- Results publication: PubMed 32173186Nardone R, Sebastianelli L, Versace V, Brigo F, Golaszewski S, Pucks-Faes E, Saltuari L, Trinka E. Effects of repetitive transcranial magnetic stimulation in subjects with sleep disorders. Sleep Med. 2020 Jul;71:113-121. doi: 10.1016/j.sleep.2020.01.028. Epub 2020 Feb 19.
- Individual participant dataSharing planned: No
Related trials for Insomnia
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
RecruitingPhase 4
The Effects of Orexin Antagonism on Fear Extinction in PTSD
Insomnia, PTSD
Not yet recruitingPhase 2
A Study of Oral SOM001 as a Safe and Effective Treatment for Adults With Chronic Insomnia in a Randomized, Controlled, Dose-finding Study
Chronic Insomnia
Active, not recruiting
Health enSuite Insomnia: an App-based Treatment for Adult Chronic Insomnia
Insomnia
Enrolling by invitation
Acute Psychological Sleep Stabilisation for Patients Hospitalised With Depression
Insomnia, Depression
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrea Goldstein Piekarski, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repeated Transcranial magnetic stimulation (rTMS) in people with Insomnia, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maryam Ahmadi, PhD (9512313891, maryamahmadi529@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insomnia Severity Index (ISI) (time frame: Insomnia severity index will be collected within one week before and within one week after the 10 sessions (over two weeks) of rTMS therapy.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06656533, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026; AzTrials last refreshed its copy on 6 Nov 2026.