Clinical trial NCT05949047: Smartphone-based Cognitive Emotion Regulation Training for Unpaid Primary Caregivers of Persons With Alzheimer's Disease
Official title: Biobehavioral Mechanisms of Smartphone-based Cognitive Emotion Regulation Training for Unpaid Primary Caregivers of Persons With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Caregivers
Emotions
Emotion Regulation
Stress
Psychological
Psychophysiology
Keywords: emotion regulation
caregiving
affective science
psychophysiology
psychoneuroimmunology
Lead sponsor: William Marsh Rice University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2023-07-17
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to the "Distancing" group, the "Reinterpretation" group, or a no regulation "Look Only" control group.
Primary purpose: BASIC_SCIENCE

Brief summary: Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) not only exact a heavy toll on patients, they also impose an enormous emotional, physical, and financial burden on unpaid, often family, caregivers. The strain of providing care for a loved one diagnosed with AD, often across several years, is associated with elevated depression risk and poorer overall health. Emotion regulation skills represent an ideal target for psychological intervention to promote healthy coping in ADRD caregivers. The project seeks to use an experimental medicine approach to test the efficacy and biobehavioral mechanisms of a novel, relatively brief, targeted, scalable, smartphone-based cognitive emotion regulation intervention aimed at improving psychological outcomes (i.e., reducing perceived stress, caregiver burden, and depressive symptoms) in ADRD unpaid primary caregivers as well as examine potential benefits of the caregiver intervention on quality of life in care recipients. Cognitive reappraisal is the ability to modify the trajectory of an emotional response by thinking about and appraising emotional information in an alternative, more adaptive way. Reappraisal can be operationalized via two primary tactics: psychological distancing (i.e. appraising an emotional stimulus as an objective, impartial observer) and reinterpretation (i.e., imagining a better outcome than what initially seemed apparent). The project will investigate the efficacy and underlying biobehavioral mechanisms of a novel, one-week cognitive reappraisal intervention in this population, with follow-up assessments at 2 weeks, 4 weeks, and 3 months. ADRD unpaid primary caregivers will be randomly assigned to receive training in either distancing, reinterpretation, or a no regulation natural history control condition, with ecological momentary assessments of self-reported positive and negative affect, remotely- collected psychophysiological health-related biomarkers (i.e., heart rate variability data) using pre-mailed Polar H10 chest bands, and health-related questionnaire reports. Distancing training is expected to result in longitudinal reductions in self-reported negative affect, longitudinal increases in positive affect, and longitudinal increases in HRV that are larger than those attributable to reinterpretation training and no-regulation control training.

Detailed description: The objective of the research is to use an experimental medicine approach to test the efficacy and biobehavioral mechanisms of a novel, relatively brief, targeted, scalable, smartphone-based cognitive emotion regulation intervention aimed at improving psychological outcomes (i.e., reducing perceived stress, caregiver burden, and depressive symptoms) in unpaid primary caregivers of persons diagnosed with Alzheimer's Disease or a related dementia (ADRD) as well as examine potential benefits of the caregiver intervention on quality of life in care recipients. Cognitive reappraisal (i.e., the ability to modify the trajectory of an emotional response by thinking about and appraising emotional information in an alternative, more adaptive way) represents a highly promising target for psychological intervention in ADRD caregivers. Reappraisal can be operationalized via two primary tactics: psychological distancing (i.e. appraising an emotional stimulus as an objective, impartial observer) and reinterpretation (i.e., imagining a better outcome than what initially seemed apparent). The project builds upon promising preliminary work to investigate the efficacy and underlying biobehavioral mechanisms of a novel, one-week cognitive reappraisal intervention in this population. ADRD unpaid primary caregivers will be randomly assigned to receive training in either distancing, reinterpretation, or a no regulation natural history control condition (Look Only), with one-week of active smartphone-based reappraisal training, with follow-up assessments at 2 weeks, 4 weeks, and 3 months, with longitudinal collection of self-reported positive and negative affect, ecological momentary assessments of daily stress, remotely-collected psychophysiological health-related biomarkers (i.e., heart rate variability data collected using a pre-mailed H10 strap and phone app using bluetooth), and health-related questionnaire reports. The study aims to mechanistically relate changes in psychological and psychophysiological function to prediction of health-relevant behavioral outcomes during a novel emotion regulation intervention never before implemented in this stressed, high risk group.

This research represents a Phase I, Stage I clinical trial. The primary endpoints are the assessments of the psychological and psychophysiological mechanisms mediating behavior change as a function of the cognitive emotion regulation intervention. Psychological mechanisms will be assessed by changes in self-reported positive and negative affect. Psychophysiological mechanisms will be investigated by analysis of heart rate variability data. The secondary endpoint is testing the efficacy of the intervention via assessment of psychological outcomes (i.e., the behavior change, as represented in changes in perceived stress, caregiver burden, and depressive symptoms), as well as care recipient quality of life.

270 ADRD unpaid primary caregivers will be recruited to participate in this study. This research involves random assignment of ADRD caregiver participants to either distancing training, reinterpretation training, or a no regulation natural history control condition (Look Only), as described above, using a parallel intervention model. In particular, the investigators will pseudorandomly assign participants to training groups via initially randomly interspersing 270 condition assignments (90 per cell) and then assigning participants in order accordingly. Male ADRD caregivers as well as caregivers from underrepresented racial and ethnic groups will be oversampled to ensure parity of male and female caregivers as well as equitable representation of underrepresented groups in the sample. Trained experimenters from the study team will administer all 3 conditions (distancing, reinterpretation, and Look Only) with equal frequency. The identity of the experimenter will be incorporated as a covariate during data analysis. Fidelity to the experimental protocol will be maintained via a standardized script for emotion regulation training, modified for each of the three conditions (Distancing, Reinterpretation, Look Only); direct PI training of the Project Coordinator and all research assistants who will acquire data on this protocol; and regular adherence monitoring via ongoing PI observation of Project Coordinator and research assistant training implementation. In addition, the investigators will audiotape training sessions (optionally, via informed consent), with PI review of a randomly-selected 10% of recordings to further ensure fidelity to the protocol.

Power Analyses

Power analysis for caregiver self-reported negative affect:

Sufficient power to assess self-reported negative affect outcomes will be achieved by recruiting 90 participants per training condition. This sample size estimate is based upon a power analysis for detecting an approximate effect size (d = 0.5) previously reported for within and between-subjects behavioral analyses of longitudinal reappraisal training data. Power analyses using this approximate effect size indicate over 95% power (alpha = 0.05) to detect within-group effects and over 90% power (alpha = 0.05) to detect between- group effects should be achieved with 70 participants per condition. Assuming all-cause attrition of 20% (which reflects a liberal upper bound, given past participant attrition rates of approximately 10% in longitudinal studies performed by the current study team), the sample size should provide sufficient power to assess this outcome. Post-attrition, the investigators expect to have analyzable complete data for 72-81 participants per condition.

Power analysis for caregiver heart rate variability (HRV):

Sufficient power to assess respiratory sinus arrhythmia outcomes will be achieved by recruiting 90 participants per training condition. This sample size estimate is based upon a power analysis using an approximate effect size (d = 0.5) previously obtained for within and between-subjects analyses of HRV data. Power analyses using this approximate effect size indicate over 95% power (alpha = 0.05) to detect within- group effects and over 90% power (alpha = 0.05) to detect between-group effects should be achieved with 70 participants per condition. Assuming all-cause attrition of 20% (which reflects a liberal upper bound given past participation attrition rates in longitudinal studies performed by the current study team of approximately 10%), the sample size should provide sufficient power to assess this outcome. Post-attrition, the investigators expect to have analyzable complete data for 72-81 participants per condition.

Power analysis for caregiver perceived stress, caregiver burden, depressive symptoms:

Sufficient power to assess questionnaire outcomes (e.g., perceived stress, caregiver burden, depressive symptoms) will be achieved by recruiting 90 participants per training condition. This sample size estimate is based upon a power analysis using an approximate effect size (d = 0.5) previously reported for within and between-subjects analyses of questionnaire reports measuring these variables (e.g., depressive symptoms; perceived stress). Power analyses using this approximate effect size indicate over 95% power (alpha = 0.05) to detect within-group effects and over 90% power (alpha = 0.05) to detect between-group effects should be achieved with 70 participants per condition. Assuming all-cause attrition of 20% (which reflects a liberal upper bound given past participation attrition rates in longitudinal studies performed by the current study team of approximately 10%), the sample size should provide sufficient power to assess this outcome. Post-attrition, the investigators expect to have analyzable complete data for 72-81 participants per condition.

Power analysis for care recipient affect and quality of life:

Sufficient power to assess care recipient affect and quality of life will be achieved by recruiting 90 participants per training condition. While the precise anticipated effect size for change over time in these care recipient measures as a function of caregiver cognitive emotion regulation training is not known and not expected to be large, a power analysis using a small effect size (d = 0.3) indicates 80% power (alpha = 0.05) to detect within-group effects should be achieved with 71 participants per condition. Assuming all-cause attrition of 20% (which reflects a liberal upper bound given past participation attrition rates in longitudinal studies performed by the current study team of approximately 10%), the sample size should provide sufficient power to assess this outcome. Post-attrition, the investigators expect to have analyzable complete data for 72-81 participants per condition.

Data Analyses

Data analysis will primarily use linear mixed models, incorporating fixed effects for Training Group (Distancing, Reinterpretation, No Regulation Control), Session, and Trial Type (for analyses involving the reappraisal task; Look Neutral, Look Negative, and Reappraise Negative), and their fixed-effect interactions, as well as a random effect consisting of an intercept (main effect) for each participant. In an exploratory follow-up, the investigators will additionally examine models using a random slope per participant. The outcome variables will be changes in self-reported positive and negative affect (via EMA) and HRV (RMSSD) (Aim 1) and changes in health-relevant behavioral outcomes (Aim 2). In these analyses, gender, age, caregiver relationship to care recipient, and baseline caregiving distress burden will be incorporated as covariates. Importantly, the investigators also anticipate having sufficient power to conduct exploratory analyses on the effect of caregiver gender and age on the hypothesized effects (all Aims) given that the investigators will ensure gender balance in each group by oversampling male caregivers (see Recruitment and Retention Plan). This information may help inform future intervention design and assessment (Stage II and beyond) that may arise from the results of this work. Aim 3 will be investigated using multilevel mediation modeling involving training group assignment as the higher-level predictor (X); self-reported positive and negative affect, and HRV data as individual-level mediators (M); and health-relevant behavior as individual-level outcome variables (Y; i.e., a 2-1-1 multilevel mediation model). Relevant covariates indicated above will be incorporated in all mediation models.

Missing data will be imputed using random forest imputation, which mines for complexities (interactions, nonlinearities) in the data while achieving more robust cross-validated prediction of missing-at-random (MAR) data. Loss to follow-up will be mitigated via systematic tracking of participant progress during the experiment (e.g., timeliness and completeness of training via Qualtrics from T1-T7; completion rate for daily EMA pings; and timeliness and completeness of questionnaires). An experimenter will directly contact participants who do not complete study components on schedule (i.e., not completing daily training, responding to fewer than 1 EMA ping per day, or not completing questionnaires on schedule) with reminders about the study schedule and assist with any questions. This checking and reminder system will be in addition to the automated SMS reminders sent via SurveySignal.

Eligibility criteria: Inclusion Criteria:

Healthy Adult Caregivers

* Unpaid primary caregiver of patient with Alzheimer's Disease/Alzheimer's Disease and Related Dementias (AD/ADRD)
* At least 18 years of age, with no maximum age, provided that all other inclusion/exclusion criteria are met
* Must be able to speak, read, and write in English
* Must be free of any current or past DSM diagnosis (i.e. healthy adults), with the exception of current or past mood or anxiety disorders or past substance-related disorders (i.e., current or past mood or anxiety disorders and/or past substance-related disorders would not represent an exclusion factor)
* Must have a smartphone. This represents any major iOS or Android-based smartphone. The smartphone will also be used for collection of ecological momentary assessment (EMA) data via SurveySignal.
* Must provide significant level of caregiving to their care recipient
* Must be at least minimally-stressed

Cognitively Impaired Adults

* Must have diagnosed with Alzheimer's Disease/Alzheimer's Disease and Related Dementias (AD/ADRD)
* Must be the care recipient of the primary caregiver who is completing the study
* Must be able to understand and willing to complete a questionnaire and the consent form
* Must have minimum level of dementia symptoms

Exclusion Criteria:

Healthy Adult Caregivers

* Current or past DSM diagnosis, with the exception of current or past mood or anxiety disorders or past substance-related disorders (i.e., current or past mood or anxiety disorders and/or past substance-related disorders would not represent an exclusion factor)
* Currently receiving psychotherapy that specifically addresses caregiver burden/distress or employs cognitive reappraisal as a major component
* Significant visual, auditory, or cognitive impairment that compromises their ability to understand and complete the task
* Caregiver participants who cease meeting inclusion criteria during the study will be dismissed from the study and compensated pro-rata.
* Has formerly participated in a study from our lab involving the same or essentially same design (e.g., former participants who provided pilot/preliminary data for this study)

Cognitively Impaired Adults

* The care recipient does not wish to participate, and/or their caregiver does not want them to participate
* Significant visual, auditory, or cognitive impairment that compromises their ability to understand and complete questionnaires, even with their caregiver's help will exclude them from the study
* Has formerly participated in a study from our lab involving the same or essentially same design (e.g., former participants who provided pilot/preliminary data for this study)

Primary outcomes:
measure: Self-reported negative affect
timeFrame: During Sessions Day 1 - Day 7; this cycle is 7 days
measure: Ecological momentary assessment of positive and negative affect
timeFrame: During Sessions Day 1 - Day 7; this cycle is 7 days
measure: Heart rate variability
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Perceived stress
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Caregiver burden
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Caregiver quality of life
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Depressive symptoms
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Difficulty in regulating emotion
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Positive and negative affect
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Interpersonal regulation
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
measure: Empathy
timeFrame: Initial training (Day 0), Day 7, Day 14, Day 28, and Month 3
Secondary outcomes:
measure: Reappraisal usage frequency
timeFrame: Initial training (Day 0)
measure: Reappraisal usage frequency
timeFrame: Day 7
measure: Reappraisal usage frequency
timeFrame: Day 14
measure: Reappraisal usage frequency
timeFrame: Day 28
measure: Reappraisal usage frequency
timeFrame: Month 3; this period one day long, 3 months after the initial visit)
measure: Quick Dementia Rating System (QDRS)
timeFrame: Initial training (Day 0)
measure: Quick Dementia Rating System (QDRS)
timeFrame: Day 7
measure: Quick Dementia Rating System (QDRS)
timeFrame: Day 14
measure: Quick Dementia Rating System (QDRS)
timeFrame: Day 28
measure: Quick Dementia Rating System (QDRS)
timeFrame: Month 3 (this period is one day long, 3 months after the initial visit)
measure: Revised Memory and Behavior Problem Checklist (RMBPC)
timeFrame: Month 3 (this period is one day long, 3 months after the initial visit)
measure: Care recipient affect
timeFrame: Initial training (Day 0)
measure: Care recipient affect
timeFrame: Day 7
measure: Care recipient affect
timeFrame: Day 14
measure: Care recipient affect
timeFrame: Day 28
measure: Care recipient affect
timeFrame: Month 3 (this period is one day long, 3 months after the initial visit)
measure: Care recipient quality of life
timeFrame: Initial training (Day 0)
measure: Care recipient quality of life
timeFrame: Day 7
measure: Care recipient quality of life
timeFrame: Day 14
measure: Care recipient quality of life
timeFrame: Day 28
measure: Care recipient quality of life
timeFrame: Month 3 (this period is one day long, 3 months after the initial visit)
Other outcomes:
Locations:
city: Houston
country: United States
facility: Rice University
state: Texas
Study officials:
affiliation: William Marsh Rice University
name: Bryan Denny, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Denny BT, Ochsner KN. Behavioral effects of longitudinal training in cognitive reappraisal. Emotion. 2014 Apr;14(2):425-33. doi: 10.1037/a0035276. Epub 2013 Dec 23.
citation: Denny BT. Getting better over time: A framework for examining the impact of emotion regulation training. Emotion. 2020 Feb;20(1):110-114. doi: 10.1037/emo0000641.
citation: Butler, M., J.E. Gaugler, K.M.C. Talley, H.I. Abdi, P.J. Desai, S. Duval, M.L. Fort, V.A. Nelson, W. Ng, J.M. Ouellette, E. Ratner, J. Saha, T. Shippee, B.L. Wagner, T.J. Wilt, and L. Yeshi, Care Interventions for People Living With Dementia and Their Caregivers. Comparative Effectiveness Review No. 231. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-2015- 00008-I.) AHRQ Publication No. 20-EHC023. 2020: Rockville, MD.
citation: Brewster P, Barnes L, Haan M, Johnson JK, Manly JJ, Napoles AM, Whitmer RA, Carvajal-Carmona L, Early D, Farias S, Mayeda ER, Melrose R, Meyer OL, Zeki Al Hazzouri A, Hinton L, Mungas D. Progress and future challenges in aging and diversity research in the United States. Alzheimers Dement. 2019 Jul;15(7):995-1003. doi: 10.1016/j.jalz.2018.07.221. Epub 2018 Sep 19.
citation: Boots LM, de Vugt ME, van Knippenberg RJ, Kempen GI, Verhey FR. A systematic review of Internet-based supportive interventions for caregivers of patients with dementia. Int J Geriatr Psychiatry. 2014 Apr;29(4):331-44. doi: 10.1002/gps.4016. Epub 2013 Aug 20.
citation: Schulz R. The Future of Caregiver Efficacy Research: Commentary on "Long-Term Outcomes of the Benefit-Finding Group Intervention for Alzheimer Family Caregivers". Am J Geriatr Psychiatry. 2019 Sep;27(9):995-997. doi: 10.1016/j.jagp.2019.04.001. Epub 2019 Apr 10. No abstract available.
citation: Godwin KM, Mills WL, Anderson JA, Kunik ME. Technology-driven interventions for caregivers of persons with dementia: a systematic review. Am J Alzheimers Dis Other Demen. 2013 May;28(3):216-22. doi: 10.1177/1533317513481091. Epub 2013 Mar 25.
citation: Berking M, Ebert D, Cuijpers P, Hofmann SG. Emotion regulation skills training enhances the efficacy of inpatient cognitive behavioral therapy for major depressive disorder: a randomized controlled trial. Psychother Psychosom. 2013;82(4):234-45. doi: 10.1159/000348448. Epub 2013 May 22.
citation: Berking M, Wupperman P, Reichardt A, Pejic T, Dippel A, Znoj H. Emotion-regulation skills as a treatment target in psychotherapy. Behav Res Ther. 2008 Nov;46(11):1230-7. doi: 10.1016/j.brat.2008.08.005. Epub 2008 Aug 30.