Randomized Controlled Trial of a Culturally-adapted Version of Thrive, a Computerized Cognitive Behavior Therapy (cCBT) Program to Treat Depressive Symptoms, Syndromes, and Disorders Among Rural Montanans
Phase: NA
Conditions: Depressive Symptoms
Sponsor: Montana State University

 
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Trial Protocol 
 
A Randomized Controlled Trial Of a 
culturally-adapted version of Thrive, a 
computerized cognitive behavior therapy 
program, for rural Montanans 
 
 
Sponser: Montana State University 
Protocol ID: MS033017-FC 
ClinicalTrials.gov identifier: NCT03244878 
 
 
 
Chief Investigator 
 
    NAME:  Mark Schure  
 
 
 
TITLE:  Assistant Professor 
    DEPT: Health & Human Development  
 
PHONE #: 406-994-3248 
    COMPLETE ADDRESS: 305 Herrick Hall, PO Box 173540, Bozeman, MT 59717 
    E-MAIL ADDRESS: mark.schure@montana.edu 
 
SIGNATURE (PI or ADVISOR): 
 
 
Co-Investigators 
 
    NAME: Sandra Bailey 
 
 
 
TITLE:  Professor 
    DEPT: Family of Consumer Sciences 
 
PHONE #: 406-994-6745 
    COMPLETE ADDRESS:  316B Herrick Hall, PO Box 173540, Bozeman MT, 59717-3540 
    E-MAIL ADDRESS: baileys@montana.edu 
  
 
    NAME: John Greist  
 
 
 
TITLE:  Professor of Psychiatry - Emeritus 
    DEPT: Psychiatry  
 
 
 
PHONE #: 608-827-2450 
    COMPLETE ADDRESS:  6515 Grand Teton Plaza, Suite 100, Madison, WI 53719 
    E-MAIL ADDRESS: jgreist@healthtechsys.com 
 
    NAME: Matt Byerly  
 
 
 
TITLE:  Professor of Psychiatry 
    DEPT: Cell Biology and Neuroscience 
 
PHONE #: 406-994-1601 
    COMPLETE ADDRESS:  319A Leon Johnson Hall, Bozeman, MT 53717 
    E-MAIL ADDRESS: mattbyerly@montana.edu 

 
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1. Background 
 
 
Montana’s high rates of poor mental health combined with low rates of access to care [1] 
indicate a pressing urgency for alternative methods to meet the mental health needs of 
Montanans. Mental health service deficits in rural and frontier Montana communities, 
compared to more urban areas are even more substantial [2] where higher poverty, lower 
educational attainment, and lower employment rates occur [3].  Montana ranks last among all 
states in population density with 55 of 56 counties defined as rural or frontier [4]. 
 
Computer-administered CBT (cCBT) programs have generally shown similar efficacy as 
clinician-administered CBT [5] with positive impacts in rural communities outside the U.S. [6]. 
Thrive is an interactive version of cCBT with a heavy emphasis on video rather than text 
content that appears to improve participant engagement, a shortcoming seen in prior cCBT 
programs [7]. Thrive users proceed at their own pace and receive personalized treatment 
sequences based on assessment responses by each patient. Thrive provides safeguards and 
guidance if the program is not working effectively.  
 
Thrive’s developmental history reflects changes in accessible technology.  Across all 
developmental versions, it has been shown to be efficacious in reducing depressive 
symptoms. First developed and studied as a desk top computer terminal administered program 
in a RCT compared with clinician CBT and wait-list control (WLC), it’s early promise was 
reflected in effect sizes of 1.37 and 1.26 for computer treated and therapist treated groups, 
respectively, compared with WLC [8]. A substantially modified version called COPE was 
administered by telephone via interactive voice response [9]. COPE was subsequently 
converted for administration on the Internet and improved by reducing text and implementing 
use of videos, making the program more engaging and effective for individuals with lower 
literacy. It has since been designed to operate on smartphone and tablet devices in addition to 
computers. To provide a gold-standard test of efficacy of cCBT in rural U.S. communities, 
RCTs are needed.  Given the high stigmatization of mental illness in remote rural communities 
[10], cCBT programs such as Thrive offer an accessible and confidential way to help people 
experiencing depressive symptoms, syndromes, and disorders in rural communities.  Our 
project addresses this need.   
 
Preliminary evidence on Thrive. Among commercially insured patients, Thrive resulted in an 
average reduction of 39% in depression severity as measured by the Patient Health 
Questionnaire-9 (PHQ-9) [11], from pre- to post-assessment (see Table). These uncontrolled 
trials indicate improvements in depression symptoms across all levels of baseline depression 
severity with marked improvements among those with moderate to severe depression.   
 
Thrive Outcomes Among Commercially Insured Patients (N = 297) 
Baseline PHQ-9 Score Range* 
  
0-4 
5-9 
10-14 
15-19 
20-27 
Total 
None 
Mild 
Moderate 
Mod 
Severe 
Severe 
Number of Enrollees with 
88 
104 
68 
29 
8 
297 

 
3
PHQ-9 Score of >2 
Mean Baseline Score 
2.4 
7.0 
11.5 
16.8 
21.9 
8.0 
Mean Endpoint Score 
2.0 
4.6 
6.5 
8.7 
12.0 
4.9 
Change in Mean Score 
-0.4 
-2.4 
-5.1 
-8.1 
-9.9 
-3.2 
% Improvement in Score 17% 
34% 
44% 
48% 
45% 
39% 
Effect Size 
0.22 
1.12 
1.82 
2.30 
2.35 
0.67 
*PHQ-9 score range based on 9 items with a 4-point response scale of 0 to 3 
 
 
 
2. Research Objectives 
 
This is a fully randomized trial of cCBT care for depression versus care as usual. The 
quantitative evaluation will be completed to achieve the following aims: 
 
1. To determine the relative effectiveness of the Thrive program to decrease depressive 
symptomatology and improve overall quality of life compared to usual care. 
2. To determine the long-term effectiveness of the Thrive program to decrease depressive 
symptomatology and improve overall quality of life 
 
 
3. Methods 
 
3.1 Design 
 
This study uses a randomized wait-list controlled design, whereby participants will be 
assigned either to receive the Thrive program immediately upon enrollment for 8 weeks or wait 
8 weeks following enrollment to receive the Thrive program. Subjects will be followed for a total 
of one year following delivery of Thrive to provide an exploratory evaluation of its long-term 
impact. During the RCT period, those randomized to the control group will receive basic 
information about depression from the National Institute of Mental Health [21], and will 
subsequently be provided access to the Thrive program at the end of the initial eight-weeks of 
the study trial. 
 
3.2 Inclusion/Exclusion Criteria 
 
3.2.1 Inclusion Criteria: Particpants must be aged 18 year or older; have residency in 
Montana, have reglar access to broadband internet, and have a score of 5 or greater on the 
Patient Health Questionnaire-9. 
 
3.2.2 Exclusion Criteria: We will exclude persons aged 17 year or younger, non-residents of 
Montana, those who do not have access to broadband internet, and have a score of 4 or lower 
on the Patient Health Questionnaire-9. 
 
3.3 Recruitment and Randomization 
Community members will be recruited for participation in the RCT via channels 
identified from key informant interviews and focus group sessions. Example channels include 

 
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state Extension agents, Facebook, identified organization email listservs, and community 
flyers. A study enrollment and assessment portal will randomly assign each participant to 
either the intervention or wait-list control (WLC) groups.  
 
3.4 Measures and data collection 
 
Primary Outcome Measure: Patient Health Questionnaire nine-item scale (PHQ-9) [11], is a 
valid assessments of depression severity  
 
Secondary Outcome Measures: Generalized Anxiety Disorder seven-item scale (GAD-7) 
[12]; Connor-Davidson Resilience ten-item Scale (CDRS-10) [13]; and, the Work and Social 
Adjustment Scale (WSAS) [14].  
 
Data are collected by self-report online and will be uploaded and de-identified through the 
Thrive database and made accessible to the PI for monitoring and analysis. Participants 
randomized to the intervention group are assessed at baseline, 4 and 8 weeks, and 6 and 12 
months from enrollment. Participants randomized to the waitlist control group are assessed at 
baseline, 4, 8, 12, and 16 weeks, and 8 and 14 months from enrollment. 
 
3.5 Statistical Analysis Plan: Analyses will use an intent-to-treat approach to examine 
difference in mean scores between intervention and control groups. Depressive 
symptomatology (PHQ-9 scores) from baseline and weeks 4 and 8 will be the primary 
continuous outcome measure.  Anxiety, Resilience, and Functional Impairment scores from 
baseline and weeks 4 and 8 will be secondary continuous outcome measures.  For the primary 
and secondary outcomes, the change over time in each outcome will be compared between 
the intervention and WLC groups using a linear mixed model analysis of repeated measures.  
A separate mixed model will be conducted on each outcome measure. Each mixed model will 
contain fixed effects terms for treatment (intervention vs. WLC), time, treatment × time 
interaction, and respective baseline measure (prior to the intervention) as a covariate.  Other 
relevant covariates will also be considered for inclusion in the mixed model.  The correlation of 
any naturally-occurring paired participants (e.g., parent/child, siblings, husband/wife, and 
partners) will be accounted for in the mixed model analysis.  Least squares (LS) means 
(adjusted treatment means) will be estimated as part of the mixed model so as to interpret the 
omnibus treatment effect (LS mean difference between treatments).  Statistical analyses will 
be performed using SAS software, version 9.4 (SAS Institute, Inc., Cary, NC).  The PROC 
MIXED procedures (mixed model approach in SAS) will make use of all available data from all 
participants from the efficacy analysis set, and provide a robust mechanism for handling data 
that are assumed missing at random [15-17].  The level of significance for all tests will be set at 
α = .05 (two-tailed).  Statistical expertise will be built into the budget for Years 1 and 2. 
 
To evaluate the long-term effects of Thrive, in an exploratory analysis, a completely 
within-subjects linear mixed model analysis of repeated measures will be used to examine the 
change in each of the primary and secondary outcomes over the 12 months following delivery 
of Thrive by combining data from both treatment groups (intervention+WLC).  In the case of 
the group randomized to Thrive, data will include assessments at baseline, 4 and 8 weeks, and 
6 and 12 months.  For the WLC group, baseline for this combined-group analysis will be 8 

 
5
weeks after randomization (i.e., immediately prior to starting Thrive) and then 4 and 8 weeks, 
and 6 and 12 months after starting Thrive.   
 
3.6 Sample Size Estimation and Power Analysis for the Primary Outcome of the Study: 
Effect sizes from the preliminary analysis of the 4 uncontrolled studies of Thrive as it relates to 
the primary continuous outcome (depressive symptomatology, as assessed by the PHQ-9) 
were consistently very large (d > 1.0).  Using a conservative estimate of effect size (d~0.30), 
an a priori sample size estimation and power analysis was performed for the repeated 
measures design/analysis in the proposed controlled study.  The results suggest that a sample 
size of 117 per group (N = 234) achieves 80% power to detect a conservative effect size of 
0.30 (Cohen’s d--standardized group mean difference) in a 2 (between-subjects) group design 
with 3 (within-subjects) repeated measurements having a compound symmetry covariance 
structure when the assumed within-subject correlation is 0.50, and the alpha level is 0.05 (two-
tailed), with a normal distribution for the test statistic.  We anticipate some dropouts [~49% 
within the first 4 weeks (the period designating an evaluable subject) after enrollment, based 
on treatment discontinuation results from Thrive].  Thus, 459 participants will be enrolled to 
allow for this expected rate of attrition with the intent of capturing a range of evaluable data for 
234 participants.  The Power Analysis and Sample Size (PASS) 2015 software, version 14.02, 
was used to carry out the sample size and power analysis [18]. 
 
 
 
4. Human Subjects Protections 
 
4.1 Risks and anticipated benefits for trial participants 
Risk posed to participants will be minimal. Cognitive Behavioral Therapy modules are 
developed to provide supportive positive messages and examples for participants to work 
through.  It is possible that participants will feel discomfort or stress in processing material and 
applying skills outside the program. Wait-list control group participants will receive standard 
National Institute of Mental Health information about depression while waiting 8 weeks for their 
access to Thrive. 
 
4.2 Informing potential participants of possible benefit and known risks 
Study recruitment flyers and the informed consent forms notify potential participants of any 
possible benefits and risks. Participants are provided the contact information of the university’s 
Institutional Review Board director and the study PI. 
 
4.3 Obtaining informed consent from participants 
Potential participants will see the electronic informed consent, which details the information 
about study participation, on the study portal webpage. They must provide an electronic 
signature to confirm their understanding of study obligations. 
 
4.4 Trial documentation 
Electronic data will be stored on secure encrypted servers and accessible only to the PI and 
study coordinator. Personal identifiable data are kept separate from health data. Paper records 
will be secured in locked file cabinets and offices.  Data records will be retained for 7 years 

 
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upon study completion. 
 
4.5 Monitoring and reporting adverse events 
The PI will regularly monitor the data and indications of adverse events related to participation 
in the trial.  If any adverse events are known to occur, the PI will promptly notify the university’s 
Instiutional Review Board to determine its relevance to the trial continuation. The Thrive 
program and the study assessment portal has prompts to help users who indicate suicidal 
ideation how to receive immediate help (see Appendix). 
 
 
5. References  
 
1. Nguyen T. Parity or disparity: The state of mental health in America. Alexandria, VA: 
Mental Health America; 2014. 
2. Huot KL, Lutfiyya MN, Akers MF, Amaro ML, Swanoski MT, Schweiss SK. A population-
based cross-sectional study of health service deficits among US adults with depressive 
symptoms. BMC Health Services Research. 2013;13(1):160. 
3. USDA Economic Research Service. State Fact Sheets: Montana Washington, DC: 
USDA; 2015 [Available from: http://www.ers.usda.gov/data-products/state-fact-
sheets/state-data.aspx?StateFIPS=30&StateName=Montana. 
4. U. S. Census Bureau. Resident Population Data: Population Density: U.S. Census 
Bureau; 2010 [Available from: http://www.census.gov/2010census/data/apportionment-
dens-text.php. 
5. Andersson G, Cuijpers P, Carlbring P, Riper H, Hedman E. Guided Internet-based vs. 
face-to-face cognitive behavior therapy for psychiatric and somatic disorders: A 
systematic review and meta-analysis. World Psychiatry. 2014;13(3):288-95. 
6. Blue Cross Blue Shield. Blue Cross Blue Shield Health Index. 2016. 
7. Gega L, Marks I, Mataix-Cols D. Computer-aided CBT self-help for anxiety and 
depressive disorders: Experience of a London clinic and future directions. Journal of 
Clinical Psychology. 2004;60(2):147-57. 
8. Selmi PM, Klein MH, Greist JH, Sorrell SP, Erdman HP. Computer-administered 
cognitive-behavioral therapy for depression. American Journal of Psychiatry. 
1990;147(1):51-6. 
9. Osgood-Hynes DJ, Greist JH, Marks IM, Baer L, Heneman SW, Wenzel KW, et al. Self-
administered psychotherapy for depression using a telephone-accessed computer 
system plus booklets: An open US-UK study. Journal of Clinical Psychiatry. 
1998;59(7):358-65. 
10. Gamm L, Stone S, Pittman S. Mental health and mental disorders—A rural challenge: A 
literature review. College Station, TX: Texas A&M University System; 2010. 
11. Kroenke K, Spitzer RL, Williams JB, Löwe B. The patient health questionnaire somatic, 
anxiety, and depressive symptom scales: A systematic review. General Hospital 
Psychiatry. 2010;32(4):345-59. 
12. Löwe B, Decker O, Müller S, Brähler E, Schellberg D, Herzog W, et al. Validation and 
standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general 
population. Medical Care. 2008;46(3):266-74. 

 
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13. Campbell-Sills L, Stein MB. Psychometric analysis and refinement of the Connor–
Davidson Resilience Scale (CD-RISC): Validation of a 10-item measure of resilience. 
Journal of Traumatic Stress. 2007;20(6):1019-28. 
14. Mundt JC, Marks IM, Shear MK, Greist JM. The Work and Social Adjustment Scale: A 
simple measure of impairment in functioning. The British Journal of Psychiatry. 
2002;180(5):461-4. 
15. Little RJ. Modeling the drop-out mechanism in repeated-measures studies. Journal of 
the American Statistical Association. 1995;90(431):1112-21. 
16. Mallinckrodt CH, Sanger TM, Dubé S, DeBrota DJ, Molenberghs G, Carroll RJ, et al. 
Assessing and interpreting treatment effects in longitudinal clinical trials with missing 
data. Biological Psychiatry. 2003;53(8):754-60. 
17. Wolfinger R, Chang M, editors. Comparing the SAS GLM and MIXED procedures for 
repeated measures. Proceedings of the Twentieth Annual SAS  Users Group 
Conference; 1998. 
18. NCSS Statistical Software. PASS 14 Power Analysis and Sample Size Software. 2015. 
 
 
 
 
 
Appendix: Safety Measures in Thrive 
 
In this document: 
- Messaging about the appropriate use of Thrive 
- The Patient Health Questionnaire (PHQ-9) in Thrive 
- Feedback for users with high PHQ-9 scores 
 
 
Messaging about the Appropriate Use of Thrive 
Before a study subject can start the Thrive curriculum, Thrive presents an “Important 
Information” page describing, in text written at the 5th grade reading level, the 
appropriate use of Thrive.  The user cannot continue in Thrive without agreeing with 
the information on this page.  See next page for a text of the Important Information 
page. 
 
The main points on the Important Information page are: 
- Thrive does not provide psychological advice, medical advice, diagnosis, or treatment 
- The user may continue to see his/her doctor  
 
 
Below: an Important Information page is the first page a study subject sees after enrolling in 
Thrive.  The subject cannot continue in Thrive without agreeing with this information. 
 
During your participation in the Thrive study, you may continue seeing your doctor. 
 

 
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People all over the world have troubles with low mood.  There is help, but no method is right 
for everyone. 
 
Thrive may help you feel better, but it does not replace your doctor.  Thrive does not give 
psychological or medical advice.  If you want a diagnosis or treatment for any 
condition, or if you are not improving, please see your doctor. 
 
Thrive is a computer program.  Instructions you get in Thrive are not given by a person.  It is 
your duty to ensure that they are right for you.  When you give information to Thrive, 
no one will review it.  Videos in Thrive of Dr. Greist may not give the only or best 
information or instructions.  Instead, they give his general opinion.  They may not be 
right for you.  If you have questions about anything in Thrive, please see your doctor. 
 
If you think you might hurt yourself or kill yourself, do one or more of these things right 
away: 
 
- Call 911 or your doctor or other healthcare provider right away 
- Go to an Emergency Room, or 
- Call the National Suicide Prevention Hotline at 1-800-273-TALK (8255) 
- Text ‘Matters’ to 741741 to start a text chat with the Crisis Text Line, or 
- Visit NowMattersNow.org to learn skills for dealing with thoughts of suicide” 
 
You may also continue using Thrive, but Thrive is not a substitute for the 5 actions above. 
 
Starting Thrive is a great step, but you should continue in Thrive only if you agree with the 
information on this page. 
 
 
(BOX) Check this box if you agree with the information on this page. 
 
 
The PHQ-9 in Thrive 
Thrive administers the PHQ-9 at baseline and subsequently every 10 days during user access 
to Thrive.  The study subject can see his/her PHQ-9 score in a chart after completing 
each PHQ-9 on the Dashboard.   
 
After the user completes a PHQ-9, Thrive evaluates the following items to determine which 
feedback to provide: 
- Number of times he/she has completed the PHQ-9 
- The user’s most recent PHQ-9 score 
- The user’s previous PHQ-9 score (if this is not the user’s first PHQ-9 score in Thrive) 
- The user’s level of activity in Thrive