Clinical trial NCT06267521: The STRENGTHEN Study
Official title: Hybrid Interventions to Optimize Neural Plasticity and Enhance Well-being: Mental Exercise, and Transcranial Electrical Stimulation With Temporal Interference: The STRENGTHEN Study - Phase 1 and 2
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cognitive Flexibility
Emotional Regulation
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2024-02-20
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: N= 48 into Phase 1, N=48 into Phase 2
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Change in Patient Health Questionnaire-9 (PHQ-9) Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in General Anxiety Disorder (GAD-7) Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in Single-item Suicide Question
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in Healthy Minds Index (HM Index)
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in the Perceived Stress Scale (PSS) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Emotional Styles Questionnaire (ESQ) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Cognitive Flexibility Inventory (CFI) Score: Alternatives Subscale
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Cognitive Flexibility Inventory (CFI) Score: Control Subscale
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Difficulties in Emotion Regulation Scale-18 (DERS-18) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in PROMIS Sleep Disturbance Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in PTSD Checklist for DSM-5 (PCL-5)
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in World Health Organization-5 (WHO-5)
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Restorative Sleep Questionnaire (RSQ) Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4)
measure: Change in Sleep Depth Question (SDQ) Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4)
measure: Change in Pittsburgh Sleep Quality Index (PSQI) Score
timeFrame: baseline, post-intervention (week 5)
measure: Change in Suicide Risk Survey
timeFrame: baseline, post-intervention (week 5)
measure: Change in Brief Suicide Cognitions Scale (B-SCS) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Passive and Active Suicidal Ideation Scale (PASIS) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in NIH Toolbox Loneliness Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in Five Facet Mindfulness Questionnaire (FFMQ) Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in Drexel Defusion Scale (DDS) Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in PROMIS Meaning and Purpose Score
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4), post-intervention (week 5), follow-up (week 20)
measure: Change in Digital Working Alliance Inventory (D-WAI) Score
timeFrame: post-intervention (week 5), follow-up (week 20)
measure: Change in Perseverative Thinking Questionnaire (PTQ) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Experiences Questionnaire's Decentering subscale (EQ-D) Score
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Experience Sampling / Ecological Momentary Assessment
timeFrame: 6 times per day for 7 days
measure: Change in Death Implicit Association Test Score
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Reversal Learning Task Score
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Multi-Source Interference Task Score
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Emotional Stroop Score: Reaction Time
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Emotional Stroop Score: Percent Correct
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Meteor Mission Score: Mean Reaction Time
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Meteor Mission Score: Coefficient of Variation
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Meteor Mission Score: Percent Correct
timeFrame: baseline, post-intervention (week 5), follow-up (week 20)
measure: Change in Emotional Persistence Task Score
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Change Your Mind Task Score: Mean Change
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Change Your Mind Task Score: Accuracy
timeFrame: baseline, post intervention (5 weeks)
measure: Change in Change Your Mind Task Score: Response Time
timeFrame: baseline, post intervention (5 weeks)
measure: Psychomotor Vigilance Task (Phase 2 only)
timeFrame: baseline, visit 3 (week 1), visit 4 (week 1), visit 5 (week 2), visit 6 (week 2), visit 7 (week 3), visit 8 (week 3), visit 9 (week 4), visit 10 (week 4)
Secondary outcomes:
measure: Change in Spectral Power Density During Stimulation-Free Sleep
timeFrame: baseline and up to 8 nights (4 nights for the low frequency group) over the 4 week intervention period following the baseline assessment
measure: Resting-state fMRI Connectivity Z-Scores
timeFrame: baseline, post intervention (5 weeks)
Other outcomes:
Locations:
city: Madison
country: United States
facility: Center for Healthy Minds
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Richard Davidson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Giulio Tononi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: