The STRENGTHEN Study

University of Wisconsin (UW)

Status: Enrolling

Conditions: Emotional Regulation; Cognitive Flexibility

Treatments: Device: Sham Stimulation in Lab; Device: Stimulation in Lab; Device: MRI Scanner; Other: Healthy Minds Program; Other: Sham Meditation Didactic Material

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06267521

L&S/PSYCHOLOGY/PSYCHOLOGY (Other Identifier)

2023-1473

Protocol Version 2/28/2025 (Other Identifier)

A487400 (Other Identifier)

AWD00000302 (Other Grant/Funding Number)

Details and patient eligibility

About

This study uses two different types of interventions including electrical brain stimulation delivered during sleep, and brief, daily meditation training. The investigators are trying to figure out whether these techniques, either alone or in combination with each other, can positively impact the brain networks that support our ability to think flexibly and to regulate our emotions. 48 participants will be enrolled into each of 2 phases and can expect to be on study for up to 9 months.

Full description

The investigators will evaluate the independent and synergistic effect of Cognitive Flexibility (CF)/Emotional Regulation (ER) - targeted meditation and CF/ER-targeted Transcranial Electrical Stimulation with Temporal Interference (TES-TI) during sleep in low-risk participants (n = 48).

After informed consent, all participants will undergo a set of baseline assessments, including self-report measures, behavioral tasks, functional and structural MRI, and a baseline in-laboratory sleep study.

Following these assessments, participants undergo four weeks of the study intervention. The participants will be assigned into one of four groups. Each group consists of 12 participants.

After completing the 4-week intervention, participants will repeat the behavioral, self-report, and imaging assessments given at baseline. Participants will also complete a 7-day ecological momentary assessment (EMA) at baseline, the week after intervention, and at 4-months following intervention. At the 4-month follow-up, participants may complete another round of self-report and behavioral measures.

The Primary Objectives are to:

• Evaluate the effects of the following on CF and ER networks:

  1. meditation practice alone
  2. meditation practice and high-dose TES-TI
  3. meditation practice and low-dose TES-TI
  4. TES-TI alone

The Secondary Objectives are to:

• Evaluate the differential synergies between Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep TES-TI intervention and the restoration of CF verses ER circuits

For Phase 2, an additional 48 participants will be recruited and will eliminate TES-TI once per week. All participants will come to the sleep laboratory for 2 nights over the 4 week intervention period.

Planned interim analysis of slow wave activity data from N=20 participants is adequately powered to evaluate whether TES-TI produces the anticipated modulation of deep sleep.

Enrollment: 96 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (Phase 1 and 2):

• Medically healthy
• English-speaking (able to provide consent and complete questionnaires)
• Citizen or legal resident

Exclusion Criteria (Phase 1):

• Any current or recent history (6 months) of any mental health diagnosis (Examples include major depression, hypomania, psychosis, schizophrenia, and bipolar disorder)
• Any current or recent (past 6 months) history of treatment for mental illness (including anti-depressant/anti anxiety medications, therapy)
• Scoring above Moderate range for Anxiety or Depression - Patient Health Questionnaire-9 (PHQ-9) greater than or equal to 15 or General Anxiety Disorder (GAD7) greater than or equal to 15
• At risk for suicide (PHQ item 9 greater than 0)
• Any current or past history of neurological disorders or acquired neurological disease (e.g. stroke, traumatic brain injury), including intracranial lesions and obstructive sleep apnea
• History of head trauma resulting in prolonged loss of consciousness; or a history of greater than 3 grade I concussions
• Current history of poorly controlled headaches including intractable or poorly controlled migraines
• Any systemic illness or unstable medical condition that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
• History of fainting spells of unknown or undetermined etiology that might constitute seizures
• History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) electroencephalogram, or family history of treatment resistant epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
• Possible pregnancy or plan to become pregnant in the next 6 months.
• Any metal in the brain, skull or elsewhere
• Any hair braid, dreadlocks, hair pieces, or extensions which cannot be taken out before the MRI scans and/or sleep stimulation sessions
• Any head coverings or headdress that participant feels uncomfortable removing for the purposes of the MRI scans and/or sleep stimulation sessions
• Any medical devices or implants (i.e. cardiac pacemaker, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible physician
• Dental implants containing metal (titanium or titanium alloys) surgically implanted post and core
• Substance use disorder within the past six months
• Any medication that may alter seizure threshold i.e., Attention-deficit/hyperactivity disorder (ADHD) stimulants (Adderall, amphetamine); Tricyclic/atypical antidepressants (amitriptyline, doxepine, imipramine, maprotiline, nortriptyline, bupropion); Antipsychotics (chlorpromazine, clozapine), Bronchodilators (theophylline, aminophylline); Antibiotics (fluoroquinolones, imipenem, penicillin, cephalosporins, metronidazole, isoniazid); Antivirals (valacyclovir, ritonavir); Over the Counter (OTC) (diphenhydramine, Benadryl)
• Claustrophobia (a fear of small or closed places)
• Back problems that would prevent lying flat for up to two hours
• Regular night-shift work (second or third shift)
• Do not have access to a smartphone or the internet
• Regular meditation practice and/or prior use of the Healthy Minds Program app
• Cannot visit the lab in-person for 7 consecutive weeks in the next year
• Permanent retainers

Additional Exclusion Criteria (Phase 2):

• Any current or recent history (6 months) of bipolar disorder, psychosis, schizophrenia. A history of stable depression or anxiety is not exclusionary.
• Mental health treatment (e.g, psychotherapy) is no longer exclusionary, although all the medication exclusions outlined above still apply

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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96 participants in 4 patient groups

Group 1: Mediation Only (Phase 1 and Phase 2)

Experimental group

Description:

* Baseline measures including imaging * Meditation plus Sham Stimulation 2 nights per week for 4 weeks * Post Intervention (week 5) measures including imaging * Follow up measures (week 20)

Treatment:

Other: Healthy Minds Program

Device: MRI Scanner

Device: Sham Stimulation in Lab

Group 2: Stimulation Only (Phase 1 and Phase 2)

Experimental group

Description:

* Baseline measures including imaging * Sham Meditation plus Stimulation in Lab 2 nights per week for 4 weeks * Post Intervention (week 5) measures including imaging * Follow up measures (week 20)

Treatment:

Other: Sham Meditation Didactic Material

Device: MRI Scanner

Device: Stimulation in Lab

Group 3: Combined, Low Frequency (Phase 1)

Experimental group

Description:

* Baseline measures including imaging * Meditation plus Stimulation in Lab 1 night per week for 4 weeks * Post Intervention (week 5) measures including imaging * Follow up measures (week 20)

Treatment:

Other: Healthy Minds Program

Device: MRI Scanner

Device: Stimulation in Lab

Group 4: Combined, High Frequency (Phase 1 and Phase 2)

Experimental group

Description:

* Baseline measures including imaging * Meditation plus Stimulation in Lab 2 nights per week for 4 weeks * Post Intervention (week 5) measures including imaging * Follow up measures (week 20)

Treatment:

Other: Healthy Minds Program

Device: MRI Scanner

Device: Stimulation in Lab