Exercise for Anxiety

Study Overview
=================
Brief Summary
-----------------
90 sedentary adults with a primary anxiety disorder and high anxiety sensitivity will be randomized to either 8 weeks of 1) low intensity exercise, or 2) flexible titration to high intensity exercise (HIE). Blinded, validated clinician-rated and patient-rated outcomes will be assessed over treatment and at 1- and 3-month follow-up. To better understand what mechanisms influence decisions to exercise in the real-world, we will use of heart rate (HR) as an objective mechanistic target for exercise intensity, examine changes in valuation of exercise through a neuroeconomics task, examine changes in interoceptive sensitivity with a heartbeat detection task, and integrate of ecological momentary assessment (EMA) to measure effects of immediate changes in mood with exercise on anxiety outcomes and adherence.

Official Title
-----------------
Optimizing Exercise for the Treatment of Anxiety

Conditions
-----------------
Anxiety

Intervention / Treatment
-----------------
* Behavioral: Titration to high intensity exercise (T-HIE)
* Behavioral: Low intensity exercise prescription


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Males and females ages 18-65 Primary psychiatric diagnosis of generalized anxiety disorder (GAD), social anxiety disorder, or panic disorder Anxiety Sensitivity Index-3 score of ≥23 (i.e., high anxiety sensitivity) Currently sedentary (≤60 minutes of moderate intensity exercise per week for the past 3 months) Body mass index <40 Able and willing to provide informed consent Exclusion Criteria Lifetime history of Bipolar I or II or any psychotic disorder Bulimia or anorexia in the past 6 months Substance use disorder in the past 3 months Current PTSD (past PTSD is allowed) High current suicide risk (active suicidal ideation with plan and intent) as indicated by a score of ≥4 on the Columbia Suicide Severity Rating Scale (C-SSRS) consistent with a need for referral to higher level of care

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Titration to high intensity exercise<br> | Behavioral: Titration to high intensity exercise (T-HIE)<br>* All participants will receive psychoeducation regarding the rationale for using exercise as a strategy to create immediate changes in mood and anxiety. Participants will be instructed in basic motivational principles (e.g., breaking up goals into smaller parts, using rewards) based on information in Exercise for Mood and Anxiety. Participants will begin at low intensity with the goal of titrating to high intensity by 2 weeks prior to the end of trial (Week 6). If a participant achieves at least 70% of the duration goal at the target heart rate, he/she will be titrated to the next dose level (moderate intensity). This will continue until high intensity exercise is achieved. Prescription is based on heart rate reserve((maximum heart rate [220-age] - resting heart rate)*intensity percent - resting heart rate. Intensity percent lower/upper limits for moderate intensity are 40-59% and for high intensity are 60-84%.<br>|
| Active Comparator: Low intensity exercise<br> | Behavioral: Low intensity exercise prescription<br>* All participants will receive psychoeducation regarding the rationale for using exercise as a strategy to create immediate changes in mood and anxiety. Participants will be instructed in basic motivational principles (e.g., breaking up goals into smaller parts, using rewards) based on information in Exercise for Mood and Anxiety. Prescription is based on heart rate reserve ((maximum heart rate [220-age] - resting heart rate)*30-39% (lower/upper limit of zone) - resting heart rate.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Anxiety Sensitivity Index-3 (ASI-3) score | The ASI-3 is an 18-item measure of fear of anxiety sensations with three subscales (physical, cognitive, social concerns). The total score ranges from 0 (lowest anxiety sensitivity) to 72 (highest anxiety sensitivity). | Baseline, Week 8 | 
| Change in Clinical Global Impressions/Severity Scale score | A validated Clinical Global Impressions/Severity Scale (CGI) anchored for anxiety disorders measures overall functioning and clinical improvement. CGI-S is rated from 1 (least disordered) to 7 (most disordered).Scores of 1 or 2 on the CGI-I at post-treatment will represent significant response. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engagement | Completion of exercise of any intensity (proportion of 75min assigned) | Week 12, Week 20 | 
| Adherence | Percentage of duration goals achieving target heart rate | Week 8, Week 12, Week 20 | 
| Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) Score | 14-item clinician-rated measure of severity of anxiety symptoms; The total score ranges from 0 (least severe anxiety symptoms) to 56 (most severe anxiety symptoms). | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Work and Social Adjustment Scale (WSAS) Score | 5 item self-report scale measing impairment in functioning with total score ranging from 0 (no impairment) to 40 (severe impairment). | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Overall Anxiety Severity and Impairment Scale (OASIS) Score | A 5-item self-report scale measuring anxiety symptom severity and impairment due to anxiety; response items are coded from 0 to 4 and can be summed to obtain a total score range from 0 (least severity and impairment) to 20 (most severity and impairment). | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Multidimensional Assessment of Interoceptive Awareness (MAIA-2) Score | A 37-item measure with 8 subscales assessing noticing bodily sensations, not distracting from bodily sensations, not worry about bodily sensations, attention regulation, emotional awareness (awareness of connection between emotions and bodily sensations), self-regulation of distress by body sensations, body listening, and trusting one's body. | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Score on Montgomery-Asberg Depression Rating Scale (MADRS) | A 10-item clinician-rated measure of depression severity. Total score ranges from 0 (normal/no symptoms) to 60 (severe depression). | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| 7 Day Physical Activity Recall Questionnaire (PAR) Score | interviewer-administered measure of self-reported weekly physical activity | Weekly from Week 0 (screening) to Week 20 | 
| Barriers Specific-Self-Efficacy Scale (BARSE) Score | 13-item measure, will assess barriers to exercise and will be used as a covariate predicting exercise engagement | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Physical Activity Enjoyment Scale (PACES) | 18-item measure assessing enjoyment of exercise | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Preferences for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q) Score | 16-item measure assessing preferences for different exercise intensities, with strong ability to differentiate preferences for HIE vs. LIE. | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Heartrate | Measured by the Fitbit Charge 3 | Weekly from week 1 to week 20 | 
| Ecological Momentary Assessment (EMA) Score | Surveys will consist of five 0-100 Likert scale items assessing mood, anxiety, motivation, energy, and enjoyment. | Weekly from week 1 to week 20 | 
| Neuroeconomics willingness-to-pay (WTP) auction task adapted for exercise | will evaluate the subjective threshold between an option's anticipated value and its cost (maximum amount WTP for an expected outcome) and is based on the Becker-DeGroot-Marschak (BDM) auction task68, modified for exercise. Participants will have the opportunity to avoid exercising for a specific timeframe (e.g., 1min, 15min) at a specific intensity (low, moderate, high). The task will first be administered on paper (21-item questionnaire), which will be computerized in line with training aims. | Week 1, Week 4, Week 8, Week 12, Week 20 | 
| Heartrate by Heartbeat Detection Task | Participants silently count their heartbeats for 6 trials of approximately 20-30 seconds ( 5 minutes) while being monitored on an EKG to assess accuracy of reporting. This will assess interoceptive accuracy and will be used as a covariate at baseline and change with intervention will be assessed over time. | Week 1, Week 4, Week 8, Week 12, Week 20 |