Stress & Resilience Study

Stress Clinical Trial

— CALSTAR  

Official title:

Identifying Social, Molecular, & Immunological Processes for Mitigating Toxic Stress & Enhancing Personalized Resilience

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06063174
• Other study ID #: OPR21101
• Status: Enrolling by invitation
• Phase: N/A
• Start date: June 30, 2023
• Est. completion date: August 15, 2024

Study information

• Verified date: September 2023
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Goal 1: The investigators will quantify lifetime stress burden and examine mechanisms linking Adverse Childhood Experiences (ACEs) and health. The investigators will quantify the early life and total lifetime stress burden of a representative sample of about 725 adults (aged 18+) across northern and southern California. In addition, the investigators will examine how prior life stress exposure and current stress levels are associated with differences in psychosocial, immune, metabolic, physiologic, and clinical outcomes for all participants at baseline.

Goal 2: The investigators will develop and test a biopsychosocial intervention using existing programs, platforms, resources, and core components from trauma and resilience research that will target five stress-related domains (i.e., cognitive response style, social relationships, eating, sleep, and physical activity) using cognitive restructuring and mindfulness, interpersonal skills training, mindful eating training, sleep training, and behavioral activation/mobility training. The investigators will then assess the efficacy and acceptability of the intervention in about 425 high stress exposure participants from Goal 1. Following their baseline assessment, about 425 participants will be randomly assigned to receive for 12 weeks (a) personalized intervention, (b) environmental education (active control) or (c) nothing (non-active control). The investigators will also assess the efficacy of the personalized intervention by comparing changes in outcomes by condition from baseline (prior to randomization) to immediately after the intervention, and then again after 12 weeks following intervention completion. The interventions will be entirely online/remote.

Description:

Aim 1: The investigators will quantify lifetime stress burden and examine mechanisms linking Adverse Childhood Experiences (ACEs) and health. The investigators will quantify the early life and total lifetime stress burden of a representative sample of about 725 adults (aged 18+) across California. In addition, the investigators will examine how prior life stress exposure and current stress levels are associated with differences in psychosocial, immune, metabolic, physiologic, and clinical outcomes for all participants at baseline.

Objective 1.1. Characterize associations between stress levels and psychosocial and clinical functioning by collecting self-report data from participants (see below) and by using any available electronic health records.

Objective 1.2. Examine cross-sectional relations between stress levels and physiological, biological, and behavioral processes using (1) immune and metabolic functioning assessed by non-invasive blood microsampling and the investigators' unique multi-omics approach, and (2) continuously monitored physiologic and behavioral functioning using smartwatches that have the ability to assess a variety of physiologic & behavioral processes (e.g., cardiac function, sleep, activity levels).

Objective 1.3. Develop a Personal Health Dashboard for processing data with an algorithm that will generate personalized results to inform individualized health risk assessments and provide an opportunity to deliver tailored clinical feedback and biopsychosocial resiliency training by targeting five key stress-related risk factors (see Aim 2).

Aim 2: Reduce ACEs-related health disparities by developing and testing a behavioral intervention for about 425 of the higher stress participants from Aim 1. To reduce negative stress-related effects and bolster resilience, the investigators will examine the acceptability and effectiveness of a 12 week, online, precision behavioral intervention.

Objective 2.1. Develop a behavioral intervention using existing programs, platforms, resources, and core components from trauma and resilience research that will target five stress-related domains (i.e., perceived stress, social relationships, diet, sleep, and physical activity) using cognitive restructuring and mindfulness, interpersonal skills training, personalized diet training, sleep training, and behavioral activation.

Objective 2.2. Assess the efficacy of the above-described intervention in about 425 high stress exposure participants from Goal 1. Following their baseline assessment, participants will be randomly assigned to receive (a) the personalized intervention (about 55 participants per stress-related domain), (b) stress & health psychoeducation/active control group, or (c) nonactive control group. For participants receiving the intervention, the investigators will identify each person's most dysregulated biobehavioral process using the comprehensive biopsychosocial data obtained from Goal 1, focusing on five major stress-related domains: cognitive response style, social relationships, eating, sleep, and physical activity. The investigators will pilot the use of online coach-assisted personalized interventions to target a dysregulated domain for each participant. The investigators will also assess the efficacy of the intervention by comparing changes in outcomes by condition from baseline (prior to randomization) to immediately after the intervention, and then again several months following intervention completion. The primary outcome of interest will be perceived stress (PSS-10). The secondary outcomes of the RCT include five domain specific surveys: the Five-Factor Mindfulness Scale short form (cognitive response style), Conflict Scale and UCLA Loneliness Scale (social relationship domain), Salzburg Stress Eating Scale (eating domain), Insomnia Severity Index (sleeping domain), and International Physical Activity Questionnaire short form (IPAQ, physical activity domain). Exploratory outcomes include the multiomics measures (including untargeted metabolomics, lipidomics, immune proteins, cytokines and the microbiome), physiological measures from the wearable device (i.e., heart rate variability), and continuous glucose monitoring measures.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 718
• Est. completion date: August 15, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A participant must meet all of the following criteria to be eligible to participate in this study:

1. Be able to understand and agree to comply with planned study procedures in English.

2. Participants must be aged 18 or over.

3. Participants must reside in the state of California.

Exclusion Criteria:

• A participant who meets any of the following criteria will be excluded from participation in this study:

History of disease(s):

1. Has a positive test result for human immunodeficiency virus (HIV) types 1 or 2 antibodies.

2. Has had a heart attack or stroke within the past year.

3. Has had and/or been treated for any type of cancer in the past two years.

Medication(s):

Participants who check off any of the following medications and/or treatment listed below over the past month will be excluded in the study.

1. Prednisolone (e.g., Omnipred, Pred Mild, Pred Forte, Orapred ODT, Veripred 20, Millipred DP)

2. Prednisone (e.g., Prednisone Intensol, Deltasone, Rayos)

3. Betamethasone (e.g., Celestone Soluspan, Sernivo, Diprolene AF, ReadySharp Betamethasone, Betaloan SUIK, Beta-1)

4. Dexamethasone (e.g., Ozurdex, Maxidex, DexPak 6 Day/10 day/13 Day, LoCort, ZonaCort, ReadySharp dexamethasone, DoubleDex)

5. Hydrocortisone (e.g., Hydrocort, Alphosyl, Aquacort, Cortef, Cortenema, and Solu-Cortef)

6. Methylprednisolone (e.g., Depo-Medrol, Solu-Medrol, Medrol, ReadySharp Methylprednisolone, P-Care D80, and P-Care D40)

7. Deflazacort (e.g., Emflaza)

8. Immunomodulators

• Cyclosporine (Sandimmune, Neoral, Gengraf, Restasis MultiDose)

• Tacrolimus (Protopic, Envarsus XR, Astagraf XL, Prograf)

• Methotrexate (Rheumatrex, Trexall, Otrexup (PF), Xatmep, Rasuvo, Mexate, MTX)

• Azathioprine (Immuran, Azasan)

• Mercaptopurine (6-MP, Purinethol, Purixan)

• Other Immunomodulators not listed above

9. Monoclonal antibody therapy

• Infliximab (Remicade)

• Etanercept (Enbrel, Benepali, Erelzi)

• Adalimumab (Humira)

• Secukinumab (Cosentyx)

• Tofacitinib (Xeljanz)

• Rituximab (Rituxan)

• Other Monoclonal antibody therapy not listed above

10. Intravenous immunoglobulin treatment (IVIG)

Related Conditions & MeSH terms

• Fractures, Stress
• Stress
• Stress Reaction
• Stress, Emotional
• Stress, Physiological
• Stress, Psychological

Intervention

Behavioral:
• Education Program
12-week online psychoeducation program on environmental pollution exposures, the health impacts and sources of these exposures, and practical ways to reduce these exposures. Participants in the active control group will receive this form of intervention.
• Think Well Program
12-week online program in which participants learn to identify negative emotion and thinking patterns and participate in live online group coaching. Participants whose thinking style domain is dysregulated will be assigned to this intervention program.
• Be Well Program
12-week online program in which participants learn about the importance of social relationships, connectedness, and interpersonal conflicts, and participate in live online group coaching. Participants whose social relationship/conflict domain is dysregulated will be assigned to this intervention program.
• Eat Well Program
12-week online program in which participants learn about mindful eating and participate in live online group coaching. Participants whose diet domain is dysregulated will be assigned to this intervention program.
• Sleep Well Program
12-week online program in which participants learn about the importance of good sleep and participate in live online group coaching. Participants whose sleep domain is dysregulated will be assigned to this intervention program.
• Move Well Program
12-week online program in which participants learn about the importance of adequate physical activity for health and participate in live online group coaching. Participants whose physical activity domain is dysregulated will be assigned to this intervention program.

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California

Sponsors (4)

Lead Sponsor	Collaborator
University of California, Los Angeles	California Initiative to Advance Precision Medicine, Stanford University, University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (25)

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Miller TR, Waehrer GM, Oh DL, Purewal Boparai S, Ohlsson Walker S, Silverio Marques S, Burke Harris N. Adult health burden and costs in California during 2013 associated with prior adverse childhood experiences. PLoS One. 2020 Jan 28;15(1):e0228019. doi: 10.1371/journal.pone.0228019. eCollection 2020. — View Citation

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Waehrer GM, Miller TR, Silverio Marques SC, Oh DL, Burke Harris N. Disease burden of adverse childhood experiences across 14 states. PLoS One. 2020 Jan 28;15(1):e0226134. doi: 10.1371/journal.pone.0226134. eCollection 2020. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in PSS-10	The primary endpoint will be the change in Perceived Stress Scale (PSS-10) score between the nonactive control, active control, and the treatment groups (combined) from screening to Follow-up 1 & 2. A meaningful clinically significant score in the PSS-10 score is a difference of 5 points. The range of the PSS-10 is 0-40, with higher scores indicating more perceived stress. As such PSS-10 change scores could range from -40 to 40. A positive PSS-10 change score indicates increased stress and is a negative outcome. A negative PSS-10 change score indicates decreased stress and is a positive outcome.	PSS-10 will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).
Secondary	Change in CSS subscale Score	The change in participants' specific intervention risk score between screening and Follow-up 1 & 2 from the Consequences of Stress scale (CSS) within intervention groups. Each CSS subscale has a range of 3-21, with higher scores indicating more dysfunction. As such, CSS subscale change scores could be from -18 to 18. A positive CSS subscale change score indicates increased dysfunction and is a negative outcome. A negative CSS subscale change score indicates decreased dysfunction and is a positive outcome.	Consequences of Stress scale will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).
Secondary	Change in Five-Factor Mindfulness Scale short form (cognitive response style domain)	The change in participants' specific domain score between screening and Follow-up 1 & 2 from the Five Factor Mindfulness Scale (FFMS) partial short form within the cognitive response style group. The FFMS-15 short form was reduced to a 6-item questionnaire to include only non-judgement and non-reactivity subscales. The scale has a range of 6-30, which higher scores indicating increased mindfulness. FFMS change scores could be from -24 to 24. A positive FFMS scale change score indicates decreased mindfulness and is a negative outcome. A negative FFMS scale change score indicated increased mindfulness and is a positive outcome.	Five-Factor Mindfulness scale will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).
Secondary	Change in Conflict Scale and UCLA Loneliness Scale (social relationship domain)	The change in participants' specific domain score between screening and Follow-up 1 & 2 from the Conflict Scale and UCLA Loneliness Scale short form within the social relationship group. The revised Conflict Scale has a range of 6-42, with higher scores indicating more conflict. Conflict scale change scores could be from -36 to 36. A positive Conflict scale change score indicates increased conflict and is a negative outcome. A negative Conflict scale change score indicates decreased conflict and is a positive outcome. The UCLA Loneliness Scale has a range of 3-9, which higher score indicating more loneliness. UCLA Loneliness Scale change scores could be from -6 to 6. A positive UCLA Loneliness scale change score indicates increased loneliness and is a negative outcome. A negative UCLA Loneliness scale change score indicates decreased loneliness and is a positive outcome.	Five-Factor Mindfulness scale will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).
Secondary	Change in Salzburg Stress Eating Scale (eating domain)	The change in participants' specific domain score between screening and Follow-up 1 & 2 from the Salzburg Stress Eating Scale (SSES) within the eating group. The scale has a range of 10-50, which higher scores indicating tendency to eat more when stressed, medium score indicating tendency to eat just as much as usual when stressed, and lower score indicating tendency to eat less when stressed. SSES change scores could be from -40 to 40. A mean score towards a medium mean score (=3) indicates tendency to eat just as much has usual when stressed and is a positive outcome. Higher or lower means indicate tendency to over and/or under eat and is a negative outcome.	Salzburg Stress Eating scale will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).
Secondary	Change in Insomnia Severity Index (sleeping domain)	The change in participants' specific domain score between screening and Follow-up 1 & 2 from the Insomnia Severity Index (ISI) within the sleep group. The scale has a range of 0-28, which higher scores indicating increased insomnia or sleep issues. ISI scale change scores could be from -28 to 28. A positive ISI scale change score indicates increased insomnia and is a negative outcome. A negative FFMS scale change score indicated decreased insomnia and is a positive outcome.	Insomnia Severity Index scale will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).
Secondary	Change in International Physical Activity Questionnaire short form (physical activity domain)	The change in participants' specific domain score between screening and Follow-up 1 & 2 from the International Physical Activity Questionnaire (IPAQ) short form within the physical activity group. The scale has two forms of output from scoring. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week). The continuous variable will be used for analysis purposes by estimating total MET minutes/week (range 0- 10080). MET minutes represent the amount of energy expended carrying out physical activity. Higher scores indicate increased level of physical activity and is a positive outcome. Lower scores indicate decreased levels of physical activity and is a negative outcome.	International Physical Activity Questionnaire scale will be assessed at all three time points during the baseline period (first 1-3 weeks of the study), follow-up1 (after 12-week intervention), and follow-up2 (at 24 week mark from baseline).