Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep

NCT04953559 | Recruiting FDA Device

• 2 other identifiers: 2007900971W81XWH-19-PRMRP-DA
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (16)

• Within-subject changes in functional connectivity and brain metabolites following administration of active or sham cTBS TMS - day 8

  Measure neurochemistry in anterior cingulate and occipitoparietal cortex using spectroscopy during MRI scan

  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

  Measure neurochemistry in anterior cingulate and occipitoparietal cortex using spectroscopy during MRI scan

  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

  Measure neurochemistry in anterior cingulate and occipitoparietal cortex using spectroscopy during MRI scan

  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

  Measure neurochemistry in anterior cingulate and occipitoparietal cortex using spectroscopy during MRI scan

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement day 15

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement

  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

  Sleep period polysomnographic (PSG) measurement (time) day 8

  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

  Sleep period polysomnographic (PSG) measurement (percentage of time) day 8

  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

  Sleep period polysomnographic (PSG) measurement (time) day 15

  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

  Sleep period polysomnographic (PSG) measurement (percentage of time) day 15

  During in-lab periods while sleeping during Overnight Visit 2 (day 15-16)

Secondary Outcomes (89)

• Karolinska Sleepiness Scale (KSS) - day 8, admin 1

  Once during cognitive testing portion of Overnight Visit 1 (day 8-9), day 8

• Karolinska Sleepiness Scale (KSS) - day 8, admin 2

  Approximately one hour after previous administration during cognitive testing portion of Overnight Visit 1 (day 8-9), day 8

• Karolinska Sleepiness Scale (KSS) - day 8, admin 3

  Approximately one hour after previous administration (2 hours after initial) during cognitive testing portion of Overnight Visit 1 (day 8-9), day 8

• Karolinska Sleepiness Scale (KSS) - day 9, admin 4

  Once during cognitive testing portion of Overnight Visit 1 (day 8-9), day 9

• Karolinska Sleepiness Scale (KSS) - day 9, admin 5

  Approximately one hour after previous administration during cognitive testing portion of Overnight Visit 1 (day 8-9), day 9

Study Arms (2)

Active cTBS first, then sham cTBS

EXPERIMENTAL

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.

Device: Active cTBS; Device: Sham cTBS

Sham cTBS first, then active cTBS

EXPERIMENTAL

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.

Device: Active cTBS; Device: Sham cTBS

Interventions

Active cTBS DEVICE

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

Active cTBS first, then sham cTBS; Sham cTBS first, then active cTBS

Sham cTBS DEVICE

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

Active cTBS first, then sham cTBS; Sham cTBS first, then active cTBS

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Psychiatry Department

Tucson, Arizona, 85724, United States

RECRUITING

Related Publications (2)

• Huskey A, Fisher JM, Hildebrand L, Negelspach D, Henderson-Arredondo K, Jankowski S, Patel SI, Chou YH, Dailey NS, Killgore WDS. Polysomnographically mediated cognitive improvements in individuals with insomnia symptoms following continuous theta-burst stimulation of the default mode network. Front Sleep. 2024 Oct 2;3:1424083. doi: 10.3389/frsle.2024.1424083. eCollection 2024.

  PMID: 41424521 DERIVED

• Hildebrand L, Huskey A, Dailey N, Jankowski S, Henderson-Arredondo K, Trapani C, Patel SI, Chen AY, Chou YH, Killgore WDS. Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep in Individuals With Insomnia Symptoms: Protocol for a Double-Blind Randomized Controlled Trial. JMIR Res Protoc. 2024 Jan 26;13:e51212. doi: 10.2196/51212.

  PMID: 38277210 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Condition Hierarchy (Ancestors)

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

Study Officials

• William D Killgore, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William D Killgore, PhD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: July 8, 2021
• Study Start: August 6, 2021
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: August 17, 2022

Record last verified: 2022-08

Locations

US (1)