Reducing Late-Life Anxiety and Improving Functioning With Self-Directed Relaxation
Phase: NA
Conditions: Anxiety Disorders
Sponsor: Palo Alto Veterans Institute for Research

Gould NARSAD Protocol  
 
1 
Study Protocol and Statistical Analysis Plan 
1. Administrative Information 
1.1 Title, Registration, versions, and revisions 
Title: Reducing Late-Life Anxiety and Improving Function with Self-Directed Relaxation 
IRB: 32239 (last approved date: 03/17/2017) 
Clinicaltrials.gov number: NCT02429778 
Funding: Brain and Behavior Research Foundation 
 
2 
Contact: Christine Gould, PhD (Principal Investigator)  
Email: Christine.Gould@va.gov 
 
3 
Background 
3.1 Behavioral, non-pharmacological treatments for anxiety have been effective in treating late-life 
anxiety and avoidance. In a meta- analysis of late-life anxiety psychotherapies, Thorp and 
colleagues (2009) found that Progressive Muscle Relaxation (PMR) resulted in the largest 
reductions in anxiety compared with waitlist controls, supportive therapy, and other efficacious 
therapies such as cognitive behavioral therapy (CBT). PMR is a component of CBT for anxiety, 
yet only one session of CBT is typically devoted to teaching PMR, which may be inadequate for 
older individuals to fully learn the skill. As such, older adults may not consolidate the techniques 
for utilizing PMR despite its potential to significantly reduce anxiety. Despite evidence in support 
of PMR for late-life anxiety (Thorp et al., 2009) and reduction of somatic symptom (e.g., Gift, 
Moore & Soeken, 1992), this intervention is not widely available to older adults. Dr. Gould began 
to address this issue by developing a self-directed version of PMR: Breathing, Relaxation, and 
Education for Anxiety Treatment in the Home Environment (BREATHE). 
 
4 
Study Summary and Aims 
4.1 Purpose: The PI developed a self-directed program to treat late-life anxiety called Breathing, 
Relaxation, and Education for Anxiety Treatment in the Home Environment (BREATHE). This 
program consists of weekly video lessons that participants watch on DVD along with weekly 
telephone check-ins. In BREATHE participants will learn two behavioral interventions: 
diaphragmatic breathing and progressive muscle relaxation (PMR). The purpose of the study is 
to examine whether the self-directed BREATHE program is superior to a wait list control in 
reducing anxiety in older adults with anxiety disorders. 
 
5 
Inclusion and Exclusion Criteria 
5.1 Inclusion Criteria: Men or women aged 60 and older who meet DSM-5 criteria for an anxiety 
disorder(s) (Generalized Anxiety Disorder, Panic Disorder, Agoraphobia, Social Anxiety Disorder 
or Anxiety Unspecified Anxiety Disorder or Anxiety Disorder Other Specified). Participants must 
understand English well-enough to participate in treatment. 
5.2 Exclusion Criteria: Comorbid psychiatric disorders are acceptable unless participant has 
Obsessive Compulsive Disorder, psychotic disorders or serious mental illness (bipolar disorder). 
Participants must not be taking benzodiazepines more than once a week. Participants with 
dementia or cognitive impairment, defined as a score of 6 or greater on the Short Blessed Test 

Gould NARSAD Protocol  
 
2 
will be excluded. Participants enrolled in other psychological or pharmacological treatment 
studies for psychiatric conditions will be excluded. 
 
6 
Study Endpoints: Assessments will occur at baseline, 4 weeks and 8 weeks.  
 
7 
Study Procedures 
7.1 Screening Procedures: A telephone interview will be conducted with potential participants to 
determine study eligibility. Potential participants will be offered the opportunity to complete 
this interview as a face-to-face interview if the participant would prefer to do so. During the 
interview, study staff will explain the study, its requirements and answer any questions that the 
potential participant has. Upon the potential participant’s willingness to be screened, study staff 
will determine whether patients meet age criteria (60+) and cognition exclusion criteria based 
on performance on the Short Blessed Test (SBT). The SBT (Katzman et al., 1983) is a weighted 6-
item brief cognitive assessment that can be administered in person or over the phone. This 
measure, also called the Blessed Orientation-Memory-Concentration Test, and scores of 0 to 5 
indicate normal cognition and scores ≥ 6 suggest the presence of cognitive impairment. The SBT 
is administered to assess for cognitive impairment, an exclusion criterion. The SBT evaluates the 
following cognitive domains: orientation, registration, attention, and memory recall. It has 
acceptable test-retest reliability, convergent validity with other cognitive measures, and high 
specificity and adequate sensitivity for the detection of dementia (Milne et al., 2008). Any 
participants who do not pass the SBT (≥ 6) will be excluded from the study at that time. 
Participants excluded due to cognitive scores will be provided the feedback that their 
performance may suggest the presence of cognitive problems, but further assessment is 
needed. Referrals will be provided to them at that time.  
 
An additional screening question about whether individuals take any benzodiazepines will be 
included in the telephone screen to assess this exclusion criteria. Participants will be excluded if 
they use short-acting benzodiazepines (lorazepam, alprazolam) twice a day or more frequently. 
Participants will be excluded if they use long-acting benzodiazepines (flurazepam, librium, 
clonazepam, diazepam, temazepam) once a day or more frequently.  
 
7.2 Baseline Visit: Participants who are deemed to meet inclusion/exclusion criteria for age, 
cognition, and benzodiazepine use will be invited to an approximately two to three hour face-to- 
face baseline assessment and paid $30. During the initial face-to- face assessment informed 
consent will be obtained and the baseline assessment visit will be completed. Those who are 
deemed not eligible for the treatment will be provided with appropriate referrals. The remaining 
assessment of inclusion/exclusion criteria will take place during the baseline assessment. 
Participants must meet DSM-5 criteria for an anxiety disorder(s) Generalized Anxiety Disorder, 
Panic Disorder, Agoraphobia, Social Anxiety Disorder or unspecified anxiety disorder. Those 
patients with Obsessive Compulsive Disorder (OCD) will be excluded as efficacious treatments 
for OCD are well established (e.g., exposure and response prevention). Assessment of anxiety 
disorders will be completed by trained study staff who use the Structured Clinical Interview for 
DSM-5 Disorders (SCID-5). At the beginning of the face-to-face baseline assessment, written 
informed consent and consent for audiotaping of the SCID-5 will be obtained. Audiotaping will 

Gould NARSAD Protocol  
 
3 
be used for supervision purposes and to assess inter-rater reliability of diagnoses. Participants 
will be allowed to continue with the study if they do not consent to audiotaping of the SCID-5 
interview.  
 
Participants with comorbid psychiatric disorders, such as depression or post-traumatic stress 
disorder, will be included. However, participants with documented diagnosis of dementia or a 
serious psychiatric disorder (psychotic disorder, schizophrenia, schizoaffective disorder, or 
bipolar disorder) of identification of serious psychiatric disorders by SCID-5 screening questions 
will be excluded. Additional baseline assessments include completion of a demographic 
questionnaire, administration of the Geriatric Anxiety Scale (GAS) to assess anxiety symptom 
severity, Activity Card Sort (ACS) to assess activity engagement, Somatic Symptom Scale – (SSS- 
8), Older Adult Social Evaluative Situations Scale (OASES), and depression symptoms measured 
with the Patient’s Health Questionnaire (PHQ-9). Comorbidity will be measured with the Deyo- 
adjusted Charlson Comorbidity Index (CCI). This is calculated from the self-report comorbidity 
questionnaire in the demographic questionnaire.  
    
Participants who do not meet SCID-5 criteria will be paid $30 and excluded from the study after 
completing the self-report measures and the ACS. Additional participants will be recruited to 
meet the goal of 40 participants randomized. 
 
7.3 Measures:  
In the baseline demographic questionnaire, basic participant characteristics including gender, 
marital status, race, and ethnicity will be collected. Additional questions about participants’ 
previous experience with relaxation, breathing training, meditation, Tai chi, and any other 
similar techniques will be assessed. The information needed about medical conditions to 
complete the Deyo-adjusted Charlson Comorbidity Index will come from the comorbidity 
questions (Katz et al., 1996) about medication conditions on the demographic questionnaire.  
 
The Structured Clinical Interview for DSM-5 Disorders is a structured interview that assess 
diagnostic criteria each DSM-5 disorder. The interview can take 90 to 120 minutes. The SCID-5 is 
included to assess inclusion and exclusion criteria.  
 
Geriatric Anxiety Scale (GAS). The GAS is a 30-item measure of somatic, cognitive, and affective 
symptoms of anxiety. The first 25 items of the measure are used to compute the total score; the 
last 5 items provide information about the content of worries or fears. Participants provide 
severity ratings for items using on a four-point Likert-type scale. The GAS is administered to 
assess severity of anxiety symptoms and is the primary outcome in this study.  
 
Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is a 9-item depression assessment rated on 
a four-point Likert-type scale with scores ranging from 0 to 27. It includes one item that inquires 
about suicide ideation. The PHQ-9 is administered to characterize participants’ depression 
symptoms.  
 
Somatic Symptom Scale (SSS-8). The SSS-8 is an 8-item somatic symptom assessment rated on a 

Gould NARSAD Protocol  
 
4 
five-point Likert-type scale with scores ranging from 0 to 32. The SSS-8 is administered to 
characterize participants’ somatic symptoms.  
 
Older Adult Social Evaluative Situations Scale (OASES). This measure is a 37-item measure that 
assess anxiety about and avoidance of social situations. This is included as a secondary outcome 
measure.  
 
Activity Card Sort (ACS). The ACS contains 80 photographs that depict the performance of 
instrumental activities, low-physical-demand leisure activities, high-physical-demand leisure 
activities, and social activities. The ACS was selected as a measure of activity engagement for the 
present study because it assesses the presence and the loss of activity. We will administer the 
ACS using an interactive sorting task (Q-sort procedure; Albert et al., 2009). Participants will be 
asked to divide the stack of photographs into a pile of activities that they currently do not 
perform and activities that they do perform. Then, participants will divide the stack of activities 
that are currently not performed into two additional piles: “never-performed” and “used-to-but-
no-longer- perform” activities. For the stack of activities that are currently performed, these will 
be divided into “hard-to-do” and “easy-to-do” activities based on a time frame of “today or the 
past 30 days.”  
 
The four piles will be used to calculate lifestyle-adjusted function (Albert et al., 2009). By 
excluding activities that participants never performed, the lifestyle-adjusted function score will 
accurately reflect loss, gain, or changes in activity participation. We also have participants select 
their top five activities that they would like to do more frequently if not experiencing anxiety. 
Participants will make ratings of these measures before and after treatment.  
 
Physiological measures are systolic and diastolic blood pressure, pulse rate, and oxygen 
saturation measured with a Welch Allyn Spot Vital Signs monitor. Five-minute resting baseline 
assessments will be obtained at baseline and post-treatment. A five-minute post-relaxation 
practice will also be obtained at post-treatment.  
 
7.4 Randomization: Participants will be randomized to BREATHE or wait list. A statistician will advise 
on completing randomization in order to obtain two equal groups. Randomization scheme will 
be created by individuals not related to the study. At the baseline visit, Dr. Gould or her research 
assistant will open a sealed envelope that contains the results of the randomization. Participants 
will not be told which group they are randomized to, but based on the differences in the active 
intervention compared with wait list; they will likely be able to ascertain what their 
randomization group is. Because of the nature of psychological interventions, it is difficult to 
achieve blindness in RCTs with psychological interventions. 
 
7.5 Study Design  
The objectives will be addressed with an 8-week randomized control  
trial (RCT) that compares a 4 week treatment, BREATHE (described  
below), and 4 weeks of practice of the intervention, progressive  
muscle relaxation, with a wait list control. Wait-list  

Gould NARSAD Protocol  
 
5 
participants will be offered the option to enroll in the active treatment after the 8 week post-
treatment assessment.  
 
7.5.1 
Protocol for BREATHE Intervention Group:  
Baseline Assessment/Pre-treatment Assessment Protocol: After the baseline assessment 
is complete, participants will be instructed on how to complete Subjective Units of 
Distress Scale (SUDS) before and after each PMR practice throughout the study. SUDS 
ratings ranging from 0 to 100 (least to most distressed) have been used to document a 
patient’s subjective experience during anxiety disorder treatments such as systematic 
desensitization and trauma- focused therapies. This measure was selected to track 
anxiety (0 = no anxiety, 100 = extreme anxiety) before and after practicing PMR. This is 
an important part of the clinical intervention in that it draws the patient’s attention to 
the changes in anxiety following the PMR intervention. SUDS may help monitor 
homework compliance and identify problems, such as relaxation-induced anxiety.  
 
Instructions on how to use and play the DVD will be provided. Portable personal DVD 
players will be lent to participants who either do not have access to a DVD player or 
would prefer to use a portable player. The surface of the DVD player will be cleaned with 
rubbing alcohol wipes to disinfect the players between participants. Participants will be 
provided their own copy of the BREATHE DVD to use throughout treatment and keep for 
future use.  
 
BREATHE Intervention Overview: BREATHE is a four week behavioral intervention that 
uses evidence- based behavioral techniques (diaphragmatic breathing and progressive 
muscle relaxation) to reduce anxiety symptoms and avoidance in older adults. BREATHE 
is designed to be aligned with the tenets of Social Learning Theory (Bandura, 1971). 
BREATHE will incorporate experiential and observational learning to promote decreased 
avoidance of identified activities. In Social Learning Theory, Bandura posits that learning 
can take place through observation of a model’s behavior in addition to the observer’s 
direct experience. Thus, decreasing reliance on avoidance as a coping strategy among 
those with anxiety disorders can be accomplished through: (1) the reduction of anxiety 
symptoms through experiential learning of relaxation and breathing skills, (2) experiential 
learning through approaching situations that are uncomfortable and avoided after using 
PMR, and (3) observation of a model who engages in an anxiety- evoking situation 
avoided by the observer. eHealth interventions for young adults use vignettes and case 
examples to model how to apply newly learned skills to overcome common life obstacles, 
such as work stress. BREATHE videos will use this format and will incorporate age- 
appropriate examples such as anxiety about engaging in exercise, health-promoting 
activities, financial worries, and worries about one’s own health and health of family 
members rather than vignettes about work, school, and interpersonal concerns that are 
less relevant to older adults (e.g., Gould & Edelstein, 2010). The combination of 
experiential and observational learning will help participants apply the skills learned in 
treatment to situations encountered in daily life. Vignettes will be used to model these 
behaviors aligned with Social Learning Theory.  

Gould NARSAD Protocol  
 
6 
 
The innovative aspect of this treatment is that BREATHE will be delivered via video 
lessons recorded on DVDs. The script for the DVD treatment is included as an 
attachment. Participants can view the DVD on a personal DVD player. The treatment also 
involves telephone check-ins during weeks one through four. The treatment will be 
delivered via DVD. The following four chapters detail the skills that make up the program. 
Each session will be turned into video lesson approximately 20-40 minutes in duration. 
During weeks 1-4 participants will view a new video module each week. Practice 
exercises are assigned each week and separate videos will be filmed to guide participants 
during practice. Homework forms are included for patients to use to record their 
practices. Participants will be asked to practice PMR twice daily as part of the behavioral 
treatment.  
 
Participants will receive a telephone call from study staff on a weekly basis to check in 
about problems with the videos or the intervention. Study staff will contact participants 
each week to troubleshoot and answer questions. Homework compliance will be 
reported by phone to study staff. Participants will be asked to report the number of 
times they practiced PMR and their SUDS ratings before and after the PMR practice 
during weekly telephone check ins. Each weekly session will consist of brief 
psychoeducation, teaching of new skills, and assigned home practice. The content of the 
weekly sessions is available from the PI or is described in the published outcome paper.  
 
7.6 Week 4 Assessment: At the end of the BREATHE treatment (week 4), participants will be 
asked to complete the GAS over the telephone. Participants will also be instructed to 
continue with home practice of PMR for four weeks. One additional reminder post card and 
telephone call at week 6 will occur to help patients with any issues that arise. After a month 
of home practice, which is 8 weeks from baseline assessment, participants will come to the 
VA for a face-to-face post-treatment assessment with study staff and will be paid $30.  
 
7.7 Post-treatment Assessment/8 weeks: At post-treatment, a 5 minute baseline measurement 
of heart rate, blood pressure, and pulse will be obtained. Then, the 16-muscle group PMR 
will be practiced by the BREATHE and the control group by briefly viewing the initial PMR 
instructions video (control only) and then following along. BREATHE participants will be 
shown the 16 muscle group practice video to follow along with. Following this practice, a 5-
min physiological measurement period will be obtained to examine physiological variables 
as a function of participant’s experience with PMR. The Anxiety disorder sections of the 
SCID-5 will be administered at post treatment to determine if participants meet criteria for 
any anxiety disorders. Then, the participants will complete the GAS to assess anxiety 
symptom severity, SSS-8 to assess somatic symptoms, PHQ-9 to measure depressive 
symptoms, OASES to assess anxiety about and avoidance of social situations, and ACS to 
assess activity engagement. We will attempt to obtain partial follow-up data from lost to 
follow- up participants, through mailed questionnaires (GAS and PHQ-9) in participants do 
not complete the final face-to-face assessment. We will solicit feedback from participants on 
their experience with BREATHE to determine what participants liked, what issues arose, and 

Gould NARSAD Protocol  
 
7 
what participants did not like about the treatment or DVDs (see attached post-treatment 
questionnaire).  
 
8 
Statistical analyses  
8.1 Baseline analyses: We compared baseline group means and distributions using χ2 and 
independent samples t-tests to determine whether randomization resulted in equivalent 
groups.  
8.2 Dropouts: We examined whether participants completing the study differed from those who 
did not complete the study (i.e., drop-outs). Efforts were made to obtain data from 
individuals who discontinued participation.  
8.3 BREATHE Intervention: Engagement with the BREATHE intervention was examined by 
estimating the intervention dose via a calculation of relaxation practices completed during 
the four-week intervention phase. The activities that participants engaged in using breathing 
or PMR skills were summarized.  
8.4 Outcome analyses: Mixed effects models were used to examine the primary and secondary 
hypotheses using intent-to-treat principles. Maximum likelihood estimation for missing 
values was used in the mixed effects models. In all models, the fixed factor was treatment 
type (BREATHE vs. wait list), with three timepoints (anxiety) or two timepoints (activities; 
depression; somatic symptoms). Effect sizes were measured using Hedges’ g to adjust for 
small sample size.  
8.5 Responder Analyses: We conducted responder analyses using intent-to-treat principles with 
participants who dropped out classified as non-responders. Responder status was defined 
by SCID-5 anxiety diagnoses. To be classified as a responder, an individual would either no 
longer meet criteria for an anxiety diagnosis or would not meet full criteria for an anxiety 
disorder at post-treatment (i.e., GAD at baseline to Anxiety Unspecified due to insufficient 
symptoms at post-treatment).  
 
9 
Publication: The outcome of this trial have been published in the American Journal of Geriatric 
Psychiatry. https://doi.org/10.1016/j.jagp.2018.12.018