Recruiting

Transcranial Magnetic Stimulation

Sponsor:

University of Arizona

Code:

NCT04953559

Conditions

Insomnia, Primary

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Not accepted

Interventions

Active cTBS

Sham cTBS

Study Details

Brief summary:

Insomnia is generally believed to be caused by excessive arousal of the brain and body. Rather than transitioning normally and quickly from wakefulness to sleep, individuals with insomnia tend to enter into a self-perpetuating cycle of self-referential thought and arousal. Brain imaging research has shown that these same internally focused self-reflective thoughts tend to activate a core system in the brain known as the Default Mode Network (DMN). The DMN is usually active when a person is internally focused, such as during daydreaming or mind wandering, but tends to be deactivated when the brain is focused on the external environment. The investigators hypothesize that excess activation and connectivity of this brain network may perpetuate internal conversations, worry, and rumination, preventing individuals with insomnia from falling asleep quickly and remaining asleep. Therefore, the goal of the present study is to use a brain stimulation technique known as transcranial magnetic stimulation (TMS) to target the DMN and slightly reduce its activation before bed. This should result in an easier time falling asleep.

For this study, the investigators will recruit 20 healthy individuals and have them sleep in the lab on two occasions. On one occasion, they will be stimulated with a type of TMS called continuous theta burst stimulation (cTBS), which will be targeted toward their DMN. They will then try to sleep in the lab while the investigators record their brain waves using a technique known as polysomnography (PSG). On the other occasion, these same individuals will undergo the same procedure, but the TMS machine will be in a deactivated mode to present a "sham" stimulation. Participants will again try to sleep in the lab following the sham treatment while being recorded with PSG. Neither the participants nor the experimenters will know which condition the participant is receiving at the time. This will only be revealed later. Additionally, all participants will receive a brain scan just before and just after the TMS procedures so that the investigators can examine changes in brain connectivity and chemistry. The investigators expect that the participants will sleep better following the cTBS than following the sham condition and that this will be associated with measurable differences in their brain connectivity and brain chemistry.

If effective, this project would have identified an innovative and novel approach for improving sleep without using drugs.

Conditions

Insomnia, Primary

Study ID

NCT04953559

Start date

Aug 6, 2021

Status verified date

Aug, 2022

Completion date

Aug 31, 2022

Anticipated

Primary completion date

Aug 31, 2022

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Healthy men and non-pregnant, non-lactating women 18-50 (inclusive) years of age, free from contraindicated diseases, medications, devices, and conditions.
  • Participants must meet the criteria for primary insomnia as determined by scores on the ISI, PSQI, and ESS. Participants must obtain two out of three of the following required scores for each questionnaire:

  • Greater than or equal to 15 for ISI (Gagnon, Belanger, Ivers, \& Morin, 2013)
  • Greater than or equal to 6 for PSQI (Buysse et al 1989)
  • Greater than or equal to 11 for ESS (Johns, 2000)

Exclusion Criteria:

  • Presence of any metal implant or medical device which may pose a safety risk for MRI or TMS (see below for examples)

  • Cardiac pacemakers
  • Metal clips on blood vessels (also called stents)
  • Artificial heart valves
  • Artificial arms, hands, legs, etc.
  • Brain stimulator devices
  • Implanted drug pumps
  • Ear implants
  • Eye implants or known metal fragments in eyes
  • Exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others)
  • Other metallic surgical hardware in vital areas
  • Certain tattoos with metallic ink
  • Certain transdermal (skin) patches such as NicoDerm (nicotine for tobacco dependence), Transderm Scop (scopolamine for motion sickness), or Ortho Evra (birth control)
  • Past or present history of sleep or breathing-related disorders such as sleep apnea (exclusion upon obtaining a score of 3 or higher on the STOP-BANG questionnaire)
  • Travel outside the time zone within the two weeks prior to enrollment visit and at any point while active in the study
  • Self-reported major medical problems including past or present history of heart problems and/or neurological problems (to include but not limited to heart murmur, heart attack, TBI, stroke, tumor, epilepsy or another seizure disorder)
  • Self-reported past or present history of cardiovascular disease (to include but not limited to arrhythmias, valvular heart disease, congestive heart failure, history of sudden cardiac death or myocardial infarction)
  • Self-reported past or present history of neurological disorder (to include but not limited to traumatic brain injury including concussions, strokes, tumors, epilepsy or another seizure disorder, amnesia for any reason, hydrocephalus, multiple sclerosis)
  • Self-reported past or present history of any seizures or seizure disorders
  • Self-reported first-degree family history (like a mother, father, or sibling) of a seizure or seizure disorder
  • Self-reported underlying acute or chronic pulmonary disease requiring daily inhaler use
  • Self-reported history of fainting spells or syncope
  • Self-reported past (at any point in the participant's history) or present psychiatric problems not including depression and/or anxiety disorders (to include but not limited to bipolar, mania, ADHD, or psychotic disorders)
  • Self-reported history of depression and/or anxiety disorders within the past 2 years
  • Self-reported suicidal ideation as indicated by a score equal to or greater than 2 on the BDI
  • Self-reported current use of certain prescription medications including Ambien, benzodiazepines, stimulants (amphetamines, medication for narcolepsy), antidepressants (SSRIs, SNRIs), antipsychotics, blood pressure medications, thyroid medications.
  • Self-reported current use of supplements that may affect sleep (to include but not limited to melatonin, valerian root, kava root)
  • Self-reported caffeine use in excess of 300 mg (e.g., approximately 8 caffeinated sodas or approximately 3-4 12-oz cups of coffee) per day on average
  • Self-reported or suspected regular nicotine use (or addiction) (defined as more than 1 cigarette or equivalent per week within the last 1 year)
  • Self-reported or suspected heavy alcohol use (minimum limit to define heavy alcohol use is 14 drinks per week)
  • Self-reported or suspected use of illicit drugs (to include but not limited to benzodiazepines, amphetamines, cocaine, opioids)
  • (Females only) Positive urine pregnancy result (Urine HCG Test results)
  • (Females only) Self-reported or suspected current breast-feeding or collecting breast-milk
  • Learned English past age 3
  • Speaking English as a non-primary language
  • Less than 9th grade education
  • Unusual sleep schedules in past six months
  • Overnight shift work
  • Inability to read and sign consent
  • Failure to cooperate with requirements of the study

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Active cTBS first, then sham cTBS

Participants complete an Enrollment Visit followed by one week of at-home actigraphy. Participants return to the lab for Overnight Visit 1 and undergo a MRI scan followed by active cTBS and then another MRI scan followed by a night of polysomnographic monitored in-lab sleep. Participants return home and complete another week of at-home actigraphy. Participants then return to the lab for Overnight Visit 2 where they undergo a MRI scan followed by sham cTBS and then another MRI scan followed by a night of polysomnographic monitored in-lab sleep.

experimental: Sham cTBS first, then active cTBS

Participants complete an Enrollment Visit followed by one week of at-home actigraphy. Participants return to the lab for Overnight Visit 1 and undergo a MRI scan followed by sham cTBS and then another MRI scan followed by a night of polysomnographic monitored in-lab sleep. Participants return home and complete another week of at-home actigraphy. Participants then return to the lab for Overnight Visit 2 where they undergo a MRI scan followed by active cTBS and then another MRI scan followed by a night of polysomnographic monitored in-lab sleep.

Interventions

Active cTBS

Active continuous theta burst (cTBS) transcranial magnetic stimulation (TMS)

Sham cTBS

Sham continuous theta burst (cTBS) transcranial magnetic stimulation (TMS)

Primary outcome measure

  • Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 8 [ Time Frame: Once during Overnight Visit 1 pre-TMS MRI scan session (day 8) ]
  • Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 8 [ Time Frame: Once during Overnight Visit 1 post-TMS MRI scan session (day 8) ]
  • Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 15 [ Time Frame: Once during Overnight Visit 2 pre-TMS MRI scan session (day 15) ]
  • Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 15 [ Time Frame: Once during Overnight 2 post-TMS MRI scan session (day 15) ]
  • Sleep onset latency (SOL) following administration of active or sham cTBS TMS - day 8 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9) ]
  • Sleep onset latency (SOL) following administration of active or sham cTBS TMS [ Time Frame: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16) ]
  • Total sleep time (TST) following administration of active or sham cTBS TMS - day 8-9 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9) ]
  • Total sleep time (TST) following administration of active or sham cTBS TMS - day 15-16 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16) ]
  • Sleep efficiency (SE) following administration of active or sham cTBS TMS - day 8-9 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9) ]
  • Sleep efficiency (SE) following administration of active or sham cTBS TMS - day 8-9 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16) ]
  • Wake after sleep onset (WASO) following administration of active or sham cTBS TMS - day 8-9 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9) ]
  • Wake after sleep onset (WASO) following administration of active or sham cTBS TMS - day 15-16 [ Time Frame: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16) ]
  • Time spent in each sleep stage following administration of active or sham cTBS TMS [ Time Frame: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9) ]
  • Percentage of time spent in each sleep stage following administration of active or sham cTBS TMS [ Time Frame: During in-lab periods while sleeping during Overnight Visit 1 (day 8-9) ]
  • Time spent in each sleep stage following administration of active or sham cTBS TMS [ Time Frame: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16) ]
  • Percentage of time spent in each sleep stage following administration of active or sham cTBS TMS [ Time Frame: During in-lab periods while sleeping during Overnight Visit 2 (day 15-16) ]

Central Contacts and Locations

Central contacts

William D Killgore, PhD

(520) 621-0605killgore@psychiatry.arizona.edu

Locations

University of Arizona Psychiatry Department

Recruiting

Tucson, Arizona, United States, 85724

Contacts

William D Killgore, PhD

520-621-0605killgore@psychiatry.arizona.edu

Principal Investigator:

William Killgore, Ph.D.

More Information

Sponsor

University of Arizona

Last update posted

Aug 17, 2022

Last verified

Aug, 2022

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Arizona on 2022-08-17.