Anxiety Sensitivity Treatment to Reduce Anxiety in Alzheimer's (ASTRA)

Treatment of Stress and Anxiety in Mild Cognitive Impairment/Mild Alzheimer's Disease and Related Dementias - RCT

The goal of this clinical trial is to test the effectiveness of a computerized anxiety sensitivity treatment (CAST) compared to a health education control (HEC) in older adults with mild cognitive impairment (MCI) or mild Alzheimer's Disease and related dementias (ADRD) and their care partners. The main questions it aims to answer are:

1. Efficacy of CAST in reducing anxiety and related symptoms among those with MCI/mild ADRD
2. Efficacy of CAST in reducing care partner burden among care partners of people living with MCI/mild ADRD
3. Explore treatment mechanisms using a multi-modal assessment battery of anxiety sensitivity and anxiety

Participants will complete six in-person visits including a baseline assessment, two intervention sessions, and three follow-up assessments at 1, 3, and 6-months posttreatment. Participants will also complete three weeks of ecological momentary assessments (EMAs) for one week prior to intervention, one week between intervention sessions, and one week after intervention.

If there is a comparison group: Researchers will compare CAST to HEC to see if CAST reduces anxiety and related symptoms in older adults with MCI/mild ADRD and care partner burden to a greater degree than HEC.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Anxiety; Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: Computerized Anxiety Sensitivity Treatment; Behavioral: Health Education Control

Detailed Description

Participants are dyads consisting of an older adult with MCI/mild ADRD and their care partner. Baseline assessment will include a neuropsychological evaluation to confirm cognitive status for the older adult with MCI/mild ADRD, a series of baseline questionnaires, and introduction to the EMA application. Dyads are randomized to either the CAST or HEC conditions. During CAST sessions, dyads view the CAST presentation and complete interoceptive exposures. An interventionist guides dyads through these sessions. During HEC, dyads view the HEC presentation and complete behavior tracking and goal-setting with the guidance of an interventionist. At both intervention sessions, dyads complete questionnaires including post assessments at the end of intervention session two. For the week prior to intervention session one, the week between the two intervention sessions, and the week after intervention session two, dyads complete daily EMAs about emotional and other factors using an application downloaded on a phone or tablet. At 1, 3, and 6-months follow-up assessments, dyads complete follow-up cognitive testing and outcome questionnaires.

• Study Type: Interventional
• Enrollment (Estimated): 388
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Norman B Schmidt, Ph.D.; Phone Number: 8506451766; Email: schmidt@psy.fsu.edu
• Study Contact Backup: Name: Frederick T Schubert, B.A.; Phone Number: 8045439845; Email: schubert@psy.fsu.edu

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32306
      • Recruiting
      • Anxiety and Behavioral Health Clinic
      • Principal Investigator: Norman B. Schmidt, Ph.D.
  • Ohio
    • Athens, Ohio, United States, 45701
      • Recruiting
      • Ohio University
      • Contact: Nik Allan, PhD
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
      • Contact: Nik Allan, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

DYAD

• Patient age 60+
• Care partner 18+
• Has care partner who will participate ("someone you have a reciprocal relationship with who provides you with emotional or physical support and helps with decision-making. This could be a spouse or significant other, relative, or close friend whom you spend a significant amount of time with.")
• Has smartphone or access to Wi-Fi

EITHER

• Score of 20 or above on the PROMIS-Anxiety short form (patient only) OR
• Score of 5 or above on SSASI (patient only) OR
• Score of 31 or above on NIH Toolbox Perceived Stress Scale score (patient only)

AND EITHER

1. Participant MoCA score is between 17 to 26

   OR

2. Participant Memory Complaint Scale score 3 or greater

   OR

3. Care partner quick dementia rating scale score between 2 to 12.5

Exclusion Criteria:

PATIENT

• Issues with seeing or hearing that would prevent reading or listening to computer presentations
• Medical conditions that would preclude participation in study
• Severe mental illness (e.g., schizophrenia, unmedicated bipolar disorder)

CARE PARTNER

• Issues with seeing or hearing that would prevent reading or listening to computer presentations
• Medical conditions that would preclude participation in study
• Severe mental illness (e.g., schizophrenia, unmedicated bipolar disorder)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Computerized Anxiety Sensitivity Treatment; CAST is a transdiagnostic cognitive behavioral therapy (CBT)-based protocol designed to address elevated anxiety sensitivity (AS), particularly the amplification of cognitive stress symptoms including perceived confusion and memory problems. CAST is a fully computerized, 1-hour intervention containing video animation and audio narration throughout, as well as interactive features (e.g., brief quizzes to promote comprehension, introduction and practice with interoceptive exposures). Procedures draw heavily on standard CBT techniques; AS, a core vulnerability for anxiety and depression is targeted using these procedures. In CAST, participants are informed that "the primary purpose of the presentation is to highlight healthier, more productive, and effective ways of dealing with stress." Through participation in the intervention, people learn adaptive long-term strategies for tolerating, coping with, and effectively reducing distress and negative emotions.	Behavioral: Computerized Anxiety Sensitivity Treatment; Brief computerized treatment for anxiety sensitivity; Other Names: CAST
Placebo Comparator: Health Education Control; HEC is a fully computerized 1-hour control condition focused on increasing healthy behaviors and decreasing unhealthy behaviors. Content includes healthy eating, hydration, sleep and rest, exercise, stress management as well as other healthy lifestyle tips. To match the interactive components in the CAST condition, behavior tracking and goal-setting are included in HEC. The HEC protocol has been used in prior studies as a control condition for CAST to account for intervention modality and time. HEC is perceived positively, with high rates of acceptability. Importantly, HEC is inert with respect to the proposed mechanism of action (AS).	Behavioral: Health Education Control; Brief computerized presentation on healthy behaviors; Other Names: HEC, Physical Health Education Training ,PHET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in anxiety sensitivity pre intervention to posttreatment.	Anxiety sensitivity will be measured using the Anxiety Sensitivity Index-3 (ASI-3). The ASI-3 is an 18-item self report measure with possible scores ranging from 0 to 72. Higher scores indicate higher anxiety sensitivity.	Baseline to immediately after the intervention
Change in anxiety pre intervention to 1-month follow-up.	Anxiety will be assessed using the Patient-Reported Outcomes Measurement Information System - Anxiety (PROMIS Anxiety) Short Form 8a self-report measure. The PROMIS Anxiety is an 8-item self report questionnaire with possible scores ranging from 8 to 40. Higher scores indicate more anxiety.	Baseline to 1-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in negative affect pre intervention to 1-month follow-up.	Negative affect will be assessed using the Positive and Negative Affect Schedule - Negative Affect (PANAS-NA). PANAS-NA is a 10-item self-report measure with possible scores ranging from 10 to 50. Higher scores indicate more negative affect.	Baseline to 1-month follow-up
Change in stress pre intervention to 1-month follow-up.	Stress will be assessed with the NIH Toolbox - Perceived Stress. The NIH Toolbox - Perceived Stress is a 10-item self-report measure with possible scores ranging from 10 to 50. Higher scores indicate more stress.	Baseline to 1-month follow-up
Change in quality of life pre intervention to 1-month follow-up.	Quality of life will be assessed with the NIH Toolbox General Life Satisfaction scale. The NIH Toolbox General Life Satisfaction scale is a 5-item self-report measure with possible scores ranging from 5 to 35. Higher scores indicate higher life satisfaction.	Baseline to 1-month follow-up
Change in depression pre intervention to 1-month follow-up.	Depression will be assessed using the PROMIS - Depression Short Form 8b. The PROMIS - Depression is an 8-item self-report measure with possible scores ranging from 8 to 40. Higher scores indicate higher level of depression.	Baseline to 1-month follow-up
Change in cognitive functioning pre intervention to 1-month follow-up.	Cognitive functioning will be assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS assesses cognitive functioning in the following domains: immediate memory, visuospatial functioning, attention, language, and delayed memory.	Baseline to 1-month follow-up
Stability of anxiety sensitivity from posttreatment to 6-month follow-up.	Anxiety sensitivity will be measured using the Anxiety Sensitivity Index-3 (ASI-3). The ASI-3 is an 18-item self report measure with possible scores ranging from 0 to 72. Higher scores indicate higher anxiety sensitivity.	Immediately after the intervention to 6-month follow-up.
Stability of anxiety from 1-month follow-up to 6-month follow-up.	Anxiety will be assessed using the Patient-Reported Outcomes Measurement Information System - Anxiety (PROMIS Anxiety) Short Form 8a self-report measure. The PROMIS Anxiety is an 8-item self report questionnaire with possible scores ranging from 8 to 40. Higher scores indicate more anxiety.	1-month to 6-month follow-up
Stability of depression from 1-month follow-up to 6-month follow-up.	Depression will be assessed using the PROMIS - Depression Short Form 8b. The PROMIS - Depression is an 8-item self-report measure with possible scores ranging from 8 to 40. Higher scores indicate higher level of depression.	1-month to 6-month follow-up
Stability of negative affect from 1-month follow-up to 6-month follow-up.	Negative affect will be assessed using the Positive and Negative Affect Schedule - Negative Affect (PANAS-NA). PANAS-NA is a 10-item self-report measure with possible scores ranging from 10 to 50. Higher scores indicate more negative affect.	1-month to 6-month follow-up
Stability of stress from 1-month follow-up to 6-month follow-up.	Stress will be assessed with the NIH Toolbox - Perceived Stress. The NIH Toolbox - Perceived Stress is a 10-item self-report measure with possible scores ranging from 10 to 50. Higher scores indicate more stress.	1-month to 6-month follow-up
Stability of quality of life from 1-month follow-up to 6-month follow-up.	Quality of life will be assessed with the NIH Toolbox General Life Satisfaction scale. The NIH Toolbox General Life Satisfaction scale is a 5-item self-report measure with possible scores ranging from 5 to 35. Higher scores indicate higher life satisfaction.	1-month to 6-month follow-up
Stability of cognitive functioning from 1-month follow-up to 6-month follow-up.	Cognitive functioning will be assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS assesses cognitive functioning in the following domains: immediate memory, visuospatial functioning, attention, language, and delayed memory.	1-month to 6-month follow-up
Change in care partner burden from pre intervention to 1-month follow-up.	Care partner burden will be assessed using the Zarit Burden Interview - Short. The Zarit Burden Interview - Short is a 12-item self-report questionnaire with a possible score range of 0 to 48. Higher scores indicate higher burden levels.	Baseline to 1-month follow-up
Change in objective measure of interoceptive fear conditioning pre to posttreatment	Interoceptive fear conditioning will be assessed with a skin conductance response (SCR) during an interoceptive exposure. Higher SCR numbers indicate higher interoceptive fear.	Baseline to immediately after the intervention
Change in Loneliness from pre intervention to 1-month follow up	Loneliness will be measured using the 10-item UCLA Loneliness Short form questionnaire. This self-report scale yields scores between 10 to 40 with higher scores indicating more significant loneliness symptoms.	Baseline through Month 1 follow up

Collaborators and Investigators

• Sponsor: Florida State University
• Collaborators: Ohio State University; Ohio University

Publications and helpful links

General Publications

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• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
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• Zarit, S., Orr, N. K., & Zarit, J. M. (1985). The hidden victims of Alzheimer's disease: Families under stress. NYU press.
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• Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998 Jun;20(3):310-9. doi: 10.1076/jcen.20.3.310.823.
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• Taylor S, Zvolensky MJ, Cox BJ, Deacon B, Heimberg RG, Ledley DR, Abramowitz JS, Holaway RM, Sandin B, Stewart SH, Coles M, Eng W, Daly ES, Arrindell WA, Bouvard M, Cardenas SJ. Robust dimensions of anxiety sensitivity: development and initial validation of the Anxiety Sensitivity Index-3. Psychol Assess. 2007 Jun;19(2):176-88. doi: 10.1037/1040-3590.19.2.176.
• Zvolensky MJ, Garey L, Fergus TA, Gallagher MW, Viana AG, Shepherd JM, Mayorga NA, Kelley LP, Griggs JO, Schmidt NB. Refinement of anxiety sensitivity measurement: The Short Scale Anxiety Sensitivity Index (SSASI). Psychiatry Res. 2018 Nov;269:549-557. doi: 10.1016/j.psychres.2018.08.115. Epub 2018 Aug 29.
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• Markley AE, Stratton KM, Cho GY, Schmidt NB, Suhr J, Sheffler JL, Nguyen C, Schubert FT, Quiles JRG, Potter MR, Meynadasy MA, Irvin SM, Allan NP. Study design and protocol for cognitive anxiety sensitivity treatment for anxiety in adults with mild cognitive impairment or dementia. Contemp Clin Trials. 2025 Sep;156:108044. doi: 10.1016/j.cct.2025.108044. Epub 2025 Aug 6.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 25, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Older Adults; Psychoeducation; Anxiety Sensitivity; Brief Treatment; Computerized Intervention; Interoceptive Exposure; Care Partner
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Anxiety Disorders; Cognitive Dysfunction; Alzheimer Disease; Dementia; NDC80 protein, human
• Other Study ID Numbers: STUDY00003432

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No