The STRENGTHEN Study

Emotional Regulation Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06267521
• Other study ID #: 2023-1473
• Secondary ID: Protocol Version
• Status: Recruiting
• Phase: N/A
• Start date: March 6, 2024
• Est. completion date: February 2025

Study information

• Verified date: May 2024
• Source: University of Wisconsin, Madison
• Contact: Tricia Denman
• Phone: 608-890-2960
• Email: tdenman[@]wisc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 and can expect to be on study for up to 9 months.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• Any current or recent history (6 months) of any mental health diagnosis (Examples include major depression, hypomania, psychosis, anxiety, 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

Related Conditions & MeSH terms

• Cognitive Flexibility
• Emotional Regulation

Intervention

Other:
• Healthy Minds Program
Participants will follow daily instructions from the Healthy Minds Program at home for four weeks, including guided meditation exercises.
• Sham Meditation Didactic Material
Participants will listen to lessons from the Healthy Minds Program at home for four weeks, which will not include any actual meditation exercises.

Device:
• Sham Stimulation in Lab
On two nights each week during the four weeks of the intervention, participants will sleep in the lab and undergo sham TES-TI stimulation for approximately 10 hours per night
• Stimulation in Lab
Participants will sleep in the lab and undergo active TES-TI stimulation for approximately 10 hours per night.
• MRI Scanner
Imaging protocol will include: structural T1-weighted and T2-weighted images, resting-state functional MRI, task-based functional MRI, and multi-shell diffusion weighted MRI, total scan time will be approximately 2 hours

Locations

Country	Name	City	State
United States	Center for Healthy Minds	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Patient Health Questionnaire-9 (PHQ-9) Score	The PHQ-9 is a 9-item inventory asking participants to rate from 0 (not at all) to 3 (nearly everyday) the frequency and intensity of depressive symptoms experienced by the respondent over the preceding two-week period. Scores range from 0 to 27 where higher scores indicate poorer patient health. Participants with scores greater than 15 will be excluded from study.	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)
Primary	Change in General Anxiety Disorder (GAD-7) Score	This 7-item inventory measures the severity of generalized anxiety disorder symptoms in individuals by asking participants to rate from 0 (not all at) to 3 (nearly everyday) the frequency and intensity of various anxiety-related symptoms experienced by the participant in the past two weeks. Scores range from 0-21 where higher scores indicate more anxiety. This study will exclude any participants who have a total score of 15 or above.	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)
Primary	Change in Single-item Suicide Question	This single-item suicide question assesses participant's suicidal ideation to respond yes or no to "Since the last time we saw you, did you seriously consider attempting suicide?".	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)
Primary	Change in Healthy Minds Index (HM Index)	The HM Index is a 17-question, 5-point scale well-being assessment that measures the four pillars of Wellbeing - Awareness, Connection, Insight, and Purpose. Means scores are from 1 to 5 with higher scores indicative of increased wellbeing.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in the Perceived Stress Scale (PSS) Score	This is a 10-item inventory asking participants to rate from 0 (never) to 4 (very often) the frequency with which they have felt various kinds of stress in the last month. Scores range from 0 to 40 with higher score indicative of higher stress.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Emotional Styles Questionnaire (ESQ) Score	This is a 24-item inventory asking participants to rate from 1 (strongly disagree) to 7 (strongly agree). Scores range from 24 - 168, higher scores are indicative of less Healthy Emotionality	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Cognitive Flexibility Inventory (CFI) Score: Alternatives Subscale	The CFI is a 20-item self-report measure to monitor how often individuals engage in cognitive behavioral thought challenging interventions. Participants rate each item from 1 (strongly disagree) to 7 (strongly agree). Scores range from 13 - 91, higher scores are indicative of increased ability to perceive multiple alternative explanations.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Cognitive Flexibility Inventory (CFI) Score: Control Subscale	The CFI is a 20-item self-report measure to monitor how often individuals engage in cognitive behavioral thought challenging interventions. Participants rate each item from 1 (strongly disagree) to 7 (strongly agree). Scores range from 7 - 49, higher scores are indicative of increased ability to perceive difficult situations as controllable.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Difficulties in Emotion Regulation Scale-18 (DERS-18) Score	The DERS-18 is a 18-item self-report measure which assesses various aspects of emotion regulation, including emotional awareness, acceptance of emotional responses, impulse control, and effective goal-directed behavior during emotional experiences using a 5-point scale from 1 (almost never) to 5 (almost always). Higher scores suggest greater problems with emotion regulation.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in PROMIS Sleep Disturbance Score	This validated assessment tool asks participants to rate 8 items that measure sleep-related difficulties using a 5-point Likert scale. Scores range from 8 to 40 with higher scores indicative of more sleep disturbance.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in PTSD Checklist for DSM-5 (PCL-5)	This 20-item self-report questionnaire is a widely used self-report questionnaire which assesses symptoms of post-traumatic stress disorder (PTSD). Participants rate from 0 (not at all) to 4 (extremely) the severity of their symptoms. Scores range from 0 to 80 with higher scores indicative of more severe PTSD symptoms.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in World Health Organization-5 (WHO-5)	This 5-item scale is a global measure of Well-Being, where higher scores reflect greater overall wellbeing (range 0-25).	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Restorative Sleep Questionnaire (RSQ) Score	This validated assessment measuring subjective perceptions of the restorative or inadequate properties of sleep will be given the morning after every sleep lab visit. The questionnaire includes 9 items rated on a 5 point scale given at the time of awakening. Scores range from 0 to100, where higher scores are indicative of better restorative sleep.	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)
Primary	Change in Sleep Depth Question (SDQ) Score	Participants will be asked to rate the depth of their prior night's sleep using 5-point Likert-type scale. How deep was your sleep? from 1 (light) to 5 (deep) after every sleep laboratory visit.	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)
Primary	Change in Pittsburgh Sleep Quality Index (PSQI) Score	This validated questionnaire evaluates subjective sleep quality. Each of the questionnaire's 19 self-reported items belongs to one of seven subcategories: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Five additional questions rated by the respondent's roommate or bed partner are included for clinical purposes and are not scored. Each component is scored 0 (no difficulty) to 3 (severe difficulty), scores ranging from 0 to 21. Higher scores are indicative of worse sleep quality.	baseline, post-intervention (week 5)
Primary	Change in Suicide Risk Survey	This battery assesses known suicide risk factors. The 13 items ask participants about their sociodemographic characteristics; past experiences with mental health symptoms; thoughts of self-harm, and self-harming actions; psychological traits. Scores range from < 0.39408955691660219 to >= 0.67215170692043313 with higher scores indicative of increased suicidality.	baseline, post-intervention (week 5)
Primary	Change in Brief Suicide Cognitions Scale (B-SCS) Score	This self-report measure assesses the suicide belief system. Using a 5-point likert scale, participants rate 6 items measuring their enduring or identity-based hopelessness rooted in their beliefs about being undesirable, their emotional state as intolerable, and life challenges as insurmountable. Scores range from 6 to 30 where higher scores are indicative of increased suicidality.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Passive and Active Suicidal Ideation Scale (PASIS) Score	This 17-item validated tool assesses participants' passive and active suicidal ideation in the past seven days using a six-point Likert scale, from 0 (Not in the past 7 days) to 5 (several times every day). Higher score reflects greater suicidal ideation.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in NIH Toolbox Loneliness Score	The NIH Toolbox Loneliness consists of 5 self-report items assessing participants' feelings of loneliness and social isolation on a 5-point Likert scale ranging from 1-5 where higher scores indicate increased loneliness.	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)
Primary	Change in Five Facet Mindfulness Questionnaire (FFMQ) Score	The FFMQ is a widely used self-report inventory that assesses mindfulness across five facets: observing, describing, acting with awareness, non-judging of inner experience, and non-reactivity to inner experience. Participants rate their agreement level with 39 items using a 5-point Likert scale. Scores range from 39 to 195 with higher scores indicative of increased mindfulness.	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)
Primary	Change in Drexel Defusion Scale (DDS) Score	This self-report measure evaluates the ability to create a mental separation or distance from one's internal experiences by asking participants to rate 10 items assessing defusion across a spectrum of internal thoughts and emotions on a 6-point scale, ranging from 0-5. Total scores range from 0 to 50 with higher scores indicative of increased defusion.	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)
Primary	Change in PROMIS Meaning and Purpose Score	This is a 37-item inventory asks participants to rate their sense of life with purpose and perceived reasons for living using a 5-point Likert scale. The current study will administer the computer adaptive test (CAT) version of the instrument, in which subsequent item choice of the system will be based on participants' previous responses. Scores range from 37 to 185 with higher scores indicative of higher feelings of meaning and purpose.	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)
Primary	Change in Digital Working Alliance Inventory (D-WAI) Score	The inventory consists of 6 items which measures the quality of the therapeutic alliance between a user and a digital mental health intervention, which is the HMP in this study. Participants rate their experience using the HMP on a 7-point scale, ranging from 1 (strongly disagree) to 7 (strongly agree). Scores range from 6 to 42 where higher scores indicate better user experience with the app.	post-intervention (week 5), follow-up (week 20)
Primary	Change in Perseverative Thinking Questionnaire (PTQ) Score	The PTQ is a self-report instrument assessing repetitive and uncontrolled thinking by asking participants to rate 15 items about the frequency, duration, and perceived uncontrollability of repetitive thoughts on a scale of 0-4. Scores range from 0 to 60. The higher the score, the higher the level of perseverative thinking or repetitive thoughts experienced by the individual.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Experiences Questionnaire's Decentering subscale (EQ-D) Score	This subscale is an 11-item scale of decentering originally developed to assess mechanisms of Mindfulness Based Cognitive Therapy (e.g., "I can separate myself from my thoughts and feelings."). The EQ-D is originally scored on a 5-point Likert scale (1 = never to 5 = all the time) where higher scores indicate increased decentering.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Experience Sampling / Ecological Momentary Assessment	The experience sampling method assesses present moment experience using a short series of questions administered on a smart phone 6 times a day for 7 days. Questions measure current emotional and cognitive state. Score range from 1-5 where higher scores indicate increased emotional state	6 times per day for 7 days
Primary	Change in Death Implicit Association Test Score	This task involves participants viewing words on a screen. Words are either related to self (e.g., "I"), others (e.g., "They"), life (e.g., "survive") or death (e.g., "die"). Like other Implicit Association Tests, participants are asked to indicate which category each word belongs to. Across the trials, self and other are paired with either life or death. The measure can be scored as an implicit marker of how easily participants associated death with themselves. Scores are greater than 2 or less than 2, with more positive values indicating a stronger association between self and death.	baseline, post intervention (5 weeks)
Primary	Change in Reversal Learning Task Score	This task involves participants viewing and choosing between two abstract visual stimuli (i.e., geometric shapes). After each choice they receive feedback that is either positive (+10) or negative (-10) feedback devoid of monetary value. Stimulus-outcome pairings are reversed over the course of the experiment.	baseline, post intervention (5 weeks)
Primary	Change in Multi-Source Interference Task Score	This task involves viewing a series of numbers and letters. Participants are asked to indicate using a button press which number was different from the other numbers. Scores are reported as percentage correct.	baseline, post intervention (5 weeks)
Primary	Change in Emotional Stroop Score: Reaction Time	This task involves viewing a series of faces and words. Participants are asked to identify the emotional expression of the faces. Percent change in reaction time is reported.	baseline, post intervention (5 weeks)
Primary	Change in Emotional Stroop Score: Percent Correct	This task involves viewing a series of faces and words. Participants are asked to identify the emotional expression of the faces. Percent correct is reported.	baseline, post intervention (5 weeks)
Primary	Change in Meteor Mission Score: Mean Reaction Time	This is a mobile measure of attention, based on the Sustained Attention to Response Task (SART), a validated, standardized laboratory task. This task lasts five minutes and measures attention regulation and sustained attention, as assessed based on reaction time, reaction time variability, and accuracy.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Meteor Mission Score: Coefficient of Variation	This is a mobile measure of attention, based on the Sustained Attention to Response Task (SART), a validated, standardized laboratory task. This task lasts five minutes and measures attention regulation and sustained attention, as assessed based on reaction time, reaction time variability, and accuracy.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Meteor Mission Score: Percent Correct	This is a mobile measure of attention, based on the Sustained Attention to Response Task (SART), a validated, standardized laboratory task. This task lasts five minutes and measures attention regulation and sustained attention, as assessed based on reaction time, reaction time variability, and accuracy.	baseline, post-intervention (week 5), follow-up (week 20)
Primary	Change in Emotional Persistence Task Score	This task involves viewing pictures categorized as neutral, positive, or negative. Participants may be asked to press a button indicating the valence category of the picture. Positive and negative affect ratings will be made on a continuous sliding scale ranging from 0 to 6.	baseline, post intervention (5 weeks)
Primary	Change in Change Your Mind Task Score: Mean Change	This task involves viewing a series of letters and numbers. Participants are asked to determine whether a target letter was a certain letter (e.g., "T"). Participants receive feedback on their choices. The feedback is not always accurate and participants are informed of this. Change range is from 0 to 1.	baseline, post intervention (5 weeks)
Primary	Change in Change Your Mind Task Score: Accuracy	This task involves viewing a series of letters and numbers. Participants are asked to determine whether a target letter was a certain letter (e.g., "T"). Participants receive feedback on their choices. The feedback is not always accurate and participants are informed of this. Accuracy is from 0 to 1.	baseline, post intervention (5 weeks)
Primary	Change in Change Your Mind Task Score: Response Time	This task involves viewing a series of letters and numbers. Participants are asked to determine whether a target letter was a certain letter (e.g., "T"). Participants receive feedback on their choices. The feedback is not always accurate and participants are informed of this. Response time is reported.	baseline, post intervention (5 weeks)
Secondary	Change in Spectral Power Density During Stimulation-Free Sleep	Change in individual participant spectral power density during stimulation free sleep will be measured and reported separately for NREM sleep (in the 1-4 Hz frequency range) and REM sleep (in the approximately 50hz frequency range) at circadian time-matched periods of baseline sleep and time-matched, stimulation free periods on each of the intervention nights.	baseline and up to 8 nights (4 nights for the low frequency group) over the 4 week intervention period following the baseline assessment
Secondary	Resting-state fMRI Connectivity Z-Scores	Resting-state fMRI connectivity will be assessed based on the Fisher-Z transformed (FZT) correlation of each seed region with all other voxels in the brain. In order to test for intervention effects, difference maps will be computed and a voxelwise analysis of the difference maps across the whole brain will be used to identify regions that might differ in connectivity between groups over time. A z-score is the number of standard deviations away from the mean.	baseline, post intervention (5 weeks)

External Links

•   Center for Healthy Minds