A Self-directed Positive Psychology Intervention for Individuals With Newly Diagnosed Multiple Sclerosis
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: Brigham and Women's Hospital

 
Version 2021.06.10 
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A Self-directed Positive Psychology Intervention for Individuals with Newly Diagnosed Multiple Sclerosis 
 
NTC06891937 
 
10.15.21 
 
 
 
 
 
 
 
 
 
 
 
 

Mass General Brigham Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
Version 2021.06.10 
 
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Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
 
Principal Investigator: 
Bonnie I. Glanz, PhD 
 
Project Title: 
A Self-directed Positive Psychology Intervention for Individuals with 
Newly Diagnosed Multiple Sclerosis 
 
Version Date: 
10.15.21 
 
 
1. 
 Background and Significance 
 
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that 
affects both physical and mental health.  Mental health comorbidities including depression and 
anxiety are common [1-2] and health-related quality of life (HRQOL) is often reduced [3-4].  
Several key elements of successful adaptation to MS have been identified including 
maintenance of emotional balance, preservation of healthy relationships, absence of 
psychological disorders, low levels of negative affect and high levels of positive affect [5]. 
 
Positive psychology (PP) uses systematic exercises such as writing a letter of gratitude or 
remembering a past success to increase the frequency and intensity of specific positive 
psychological constructs such as positive affect and optimism [6-7].  We have previously 
demonstrated the feasibility and acceptability of a five-week, at-home, trainer-guided PP 
intervention for individuals with MS [8].  The intervention was associated with significantly 
greater increases in positive affect, optimism, general health and resilience and decreases in 
anxiety in the intervention group compared to the controls.  Despite the benefits of the  
trainer-guided PP trial, the program has several limitations.  First, it requires funding for a 
dedicated study trainer limiting its scalability.  Second, the improvements seen following the 
completion of the PP exercises may have been related to engagement with the study trainer 
and not the PP program itself.  Third, the individuals who participated in the trial had a mean 
disease duration of more than 20 years and it is not clear if the observed findings apply across 
the disease course.   
 
We would like to evaluate the feasibility, acceptability and efficacy of a self-guided version of 
the PP intervention in individuals with recently diagnosed with MS.  An MS diagnosis creates a 
crisis for the individual and his/her family.  Typical initial emotional responses include fear, 
denial, anger and resentment [9].  The introduction of techniques to increase positive 
emotional experiences early on in the disease course might promote successful adaptation to 
living with MS.  If we are able to demonstrate the feasibility, acceptability and efficacy of a self-

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directed PP program, it could be made available to all newly diagnosed patients seen at the 
Brigham Multiple Sclerosis Center. 
 
2. 
Specific Aims and Objectives  
 
Specific Aim 1: Evaluate the feasibility and acceptability of a five-week self-directed PP training 
intervention for newly diagnosed patients with MS. We will assess the feasibility of the 
intervention by calculating the proportion of subjects who complete four of the five weekly 
exercises.  We will determine the acceptability of each exercise by having subjects rate the ease 
and utility of each exercise after it is completed.  
 
Specific Aim 2: Examine the efficacy of PP training to improve positive affect, emotional 
function and HRQOL.  We will compare positive affect in subjects in the intervention and 
control group at the completion of the intervention phase.  We will also assess between-group 
differences in depression, anxiety, fatigue, resilience and HRQOL following the intervention 
phase. 
 
Specific Aim 3:  Determine if improvements in positive affect, emotional function and HRQOL 
following PP training are maintained. For subjects in the intervention group who demonstrate a 
benefit from PP intervention, we will determine if that benefit is maintained by comparing 
positive affect, depression, anxiety, fatigue, resilience and HRQOL at the completion of the 
intervention and extension phases. 
 
 
3. 
General Description of Study Design 
 
This is a phase I randomized controlled trial (RCT) to examine the feasibility, acceptability and 
efficacy of a self-directed PP training intervention to increase positive affect in newly diagnosed 
patients with MS.  The RCT will include a five-week intervention phase and a five-week  
extension phase. 
 
 
 

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Schema: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Completion of patient-reported 
outcome (PRO) measures  
RANDOMIZATION 
5 Weeks of self-directed PP 
training and weekly calls 
No study activities 
Completion of PRO measures 
No study activities 
5 Weeks of self-directed PP 
training and weekly calls 
Completion of PRO measures 
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Intervention Group  
Waitlist Control Group 
30 patients with newly diagnosed MS 

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4. 
Subject Selection 
 
Thirty subjects with newly diagnosed MS will be enrolled at the Brigham MS Center.   
 
Inclusion criteria: 
1. Diagnosis of MS according to the McDonald 2017 diagnostic criteria with onset of 
symptoms within the last 2 years 
2. Age 18-65 
3. Ability to speak, read and write in English 
 
Exclusion criteria: 
1. Moderate or marked cognitive abnormalities identified by the treating neurologist 
during routine clinical visits to the Brigham MS Center that would preclude meaningful 
participation in the PP exercises.  
 
All newly diagnosed MS patients seen at the Brigham MS Center will be eligible to participate.  
Patients will be approached by their physicians at the time of their routine clinical visits to the 
center.  Interested individuals will meet with a member of the research staff to learn about the 
study in more detail.  Flyers will also be posted at the Brigham MS Center. 
  
 
5. 
Subject Enrollment 
 
Individuals with MS will be given a copy of the consent document to review.  They will have the 
opportunity to discuss the study with their physician as well as other members of the research 
study staff prior to giving consent.  Individuals may choose to enroll at the time of their clinical 
visit, or they may enroll at a later date.  Consent will be obtained by study investigators or 
research coordinators listed on the protocol.   
 
6. 
STUDY PROCEDURES 
 
Enrollment Visit (60 minutes)  
Subjects will be enrolled at the Brigham MS Center at the Brigham and Women’s Hospital.  At 
enrollment, subjects will be consented and assigned a study subject ID.  Subjects will complete 
a battery of PRO measures in REDCap, a secure web application for building and managing 
online surveys.  The PRO measures include: 
 
1. Positive and Negative Affect Scale (PANAS) [11] is comprised of two 10-item mood scales, 
one measuring positive affect and the other negative affect.   
 
2. Life Orientation Test-Revised (LOT-R) [12] is a 6-item measure of optimism and pessimism 
and the most widely used measure of optimism. 
 

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3. NeuroQoL [13] is a set of self-report measures developed through a collaborative, multisite 
NINDS-sponsored research initiative to construct psychometrically-sound and clinically-
relevant HRQOL tools for individuals with neurological conditions such as stroke, MS and 
Parkinson’s disease.  It covers 12 domains including Ability to Participate in Social Roles and 
Activities, Anxiety, Cognitive Function, Depression, Emotional and Behavioral Dyscontrol, 
Fatigue, Lower Extremity Function, Positive Affect and Well-Being, Satisfaction with Social 
Roles and Activities, Sleep, Stigma and Upper Extremity Function.   
 
4. Brief Resilience Scale (BRS) [14] is a 6-item scale that measures the ability to bounce back or 
recover from stress.  
 
After enrollment, a computerized random number generator will be used to randomize subjects 
to the intervention or control group.  
 
Intervention Phase (5 weeks)  
In the intervention phase (Phase I: Weeks 1-5), subjects randomized to the intervention group 
will be given the study participant manual and asked to set up a time for weekly phone calls 
with the study coordinator.  They will complete five weeks of PP exercises, one exercise per 
week. They will be asked to rate their mood prior to and after completing each exercise.  They 
will also be asked to rate the ease and utility of each exercise. The weekly calls with the study 
coordinator will be used to document and discuss the ease and utility scores recorded by 
subjects at the completion of the weekly exercise.   The control group will have no study 
activities during the intervention phase and will be considered a wait-list control.  At the 
completion of the intervention phase, all subjects will be emailed a link to complete PRO 
measures in REDCap.  
 
Extension Phase (5 weeks) 
In the extension phase (Phase II: Weeks 6-10), subjects in the control group will receive their 
study participant manual in the mail. They will be contacted by the study coordinator to set up 
weekly phone calls.  They will complete the PP intervention as described above. The 
intervention group will complete no study activities in the extension phase.  At the completion 
of the extension phase, all subjects will be emailed a link to complete PRO measures.  
 
Intervention: The PP intervention consists of five weeks of self-directed PP training using the 
following exercises: 
 
1. Gratitude for positive events:  Recall three positive events that occurred in the past 
week and write about the events and how the events made you feel. 
 
2. Personal strengths:  Complete a brief survey of personal strengths and select a strength 
such as perseverance or humility and use it deliberately in the next 24 hours. Write 
about how you used the strength and how you felt while using it. 
 

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3. Gratitude letter:  Recall another individual’s kind act that resulted in joy, relief, serenity 
or other positive feelings. Write a letter to the person describing feelings of gratitude 
associated with this event. 
 
4. Enjoyable and meaningful activities:  Intentionally complete three acts in a single day – a 
pleasurable act done alone, a pleasurable act done with others and a meaningful or 
important act. 
 
5. Remembering past successes:  Focus on a time when you experienced success and write 
about the event and the positive feelings and thoughts you had during the event 
 
These exercises have all been described by Huffman et al.  [10, 15].  Exercises may require 
anywhere from 15 minutes to several hours to complete.   
 
7. 
Risks and Discomforts 
 
There are no major risks associated with participating in the study.  Subjects may experience 
discomfort writing about emotional aspects of their lives.  If they do experience discomfort, 
they may choose not to complete the weekly PP assignments.  If they feel their participation is 
becoming too burdensome or is exacerbating ongoing symptoms, they have the option to 
decline further participation and withdraw from the study.  They may also be referred to a 
mental health provider at the Brigham MS Center. 
 
 
8. 
Benefits 
 
This is a pilot study designed to determine the feasibility, acceptability and efficacy of a self-
directed PP training program for individuals with newly diagnosed MS.  If the results suggest 
that self-directed PP training is feasible, acceptable and effective, it may be offered as a no cost, 
innovative tool for increasing positive affect, decreasing depression and anxiety and improving 
HRQOL in patients with newly diagnosed MS. 
 
 
 
9. 
Statistical Analysis 
 
To assess the feasibility of the intervention (Specific Aim 1), our goal is to demonstrate that the 
proportion who will complete four out of five exercises is greater than 0.5. Given our sample 
size of 30 subjects, we will have 80% power to detect a difference if the true proportion of 
subjects who will complete four out of five exercises is 0.75 using a one sample binomial test of 
proportions (Stata routine: power oneproportion).  For the comparison of the treatment groups 
in terms of PRO measures (Specific Aim 2), the intervention effect will be estimated using 
analysis of covariance (ANCOVA) model.  In the ANCOVA model, the post-intervention scores 

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will be compared between the groups controlling for baseline scores. All outcome measures 
(PANAS, LOT-R, NeuroQoL and BRS) will be compared using the same model. To assess whether  
benefits of the PP intervention are maintained at 10 weeks (Specific Aim 3), we will first 
calculate the change from baseline to week 5 for each of the outcome measures. For the 
subjects who experience a benefit of the intervention, we will then assess if at least 50% of the 
benefit was maintained at the 10-week time point. The proportion of subjects who maintained 
the benefit will be reported. 
 
10.   Monitoring and Quality Assurance 
 
Bonnie Glanz, the PI, will be responsible for assuring the validity and integrity of the data 
collected, and adherence to the IRB-approved protocol.  The study team will meet weekly to 
review subject recruitment, subject satisfaction and study progress.  Adverse events associated 
with the study will be reported to the PI within 24 hours of knowledge of the event.  The PI will 
report adverse events or other unanticipated problems to PHRC as described in the PHRC policy 
on Adverse Event Reporting and Unanticipated Problems Involving Risks to Subjects or Others. 
 
11.   Privacy and Confidentiality 
 
☒ Study procedures will be conducted in a private setting 
☒ Only data and/or specimens necessary for the conduct of the study will be collected 
☒ Data collected (paper and/or electronic) will be maintained in a secure location with appropriate 
protections such as password protection, encryption, physical security measures (locked 
files/areas) 
☐ Specimens collected will be maintained in a secure location with appropriate protections (e.g. 
locked storage spaces, laboratory areas) 
☒ Data and specimens will only be shared with individuals who are members of the IRB-approved 
research team or approved for sharing as described in this IRB protocol 
☒  Data and/or specimens requiring transportation from one location or electronic space to 
another will be transported only in a secure manner (e.g. encrypted files, password protection, 
using chain-of-custody procedures, etc.) 
☒   All electronic communication with participants will comply with Mass General Brigham secure 
communication policies 
☒ Identifiers will be coded or removed as soon as feasible and access to files linking identifiers 
with coded data or specimens will be limited to the minimal necessary members of the research 
team required to conduct the research 
☒ All staff are trained on and will follow the Mass General Brigham policies and procedures for 
maintaining appropriate confidentiality of research data and specimens 
☒ The PI will ensure that all staff implement and follow any Research Information Service Office 
(RISO) requirements for this research 
☐ Additional privacy and/or confidentiality protections 
 
 
 
 

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12.   References 
 
1. 
Marrie, R.A., et al., The burden of mental comorbidity in multiple sclerosis: frequent, 
underdiagnosed, and undertreated. Mult Scler, 2009. 15(3): p. 385-92. 
2. 
Korostil, M. and A. Feinstein, Anxiety disorders and their clinical correlates in multiple 
sclerosis patients. Mult Scler, 2007. 13(1): p. 67-72. 
3. 
Benito-Leon J, Morales JM, Rivera-Navarro J, Mitchel A.  A review about the impact of 
multiple sclerosis on health-related quality of life.  Disabil Rehabil 2003. 25: 1291-1303.  
4. 
Healy, B.C., et al., The impact of a recent relapse on patient-reported outcomes in 
subjects with multiple sclerosis. Qual Life Res, 2012. 21(10): p. 1677-84. 
5. 
Dennison, L., R. Moss-Morris, and T. Chalder, A review of psychological correlates of 
adjustment in patients with multiple sclerosis. Clin Psychol Rev, 2009. 29(2): p. 141-53. 
6. 
Seligman, M.E.P., Learned Optimism: How to Change Your mind and Your Life. 1991, 
New York: Alfred A. Knopf. 
7. 
Sin, N.L. and S. Lyubomirsky, Enhancing well-being and alleviating depressive symptoms 
with positive psychology interventions: a practice-friendly meta-analysis. J Clin Psychol, 
2009. 65(5): p. 467-87. 
8. 
Freedman ME, Healy BC, Huffman JC, Chitnis T, Weiner HL, Glanz BI.  An at-home 
positive psychology intervention for individuals with multiple sclerosis.  Int J MS Care, 
2021.  23: p. 128-134. 
9. 
Murray TJ, Sauners CS, Holland NJ.  Multipel Sclerosis: A Guide for the Newly Diagnosed 
4t ed. New York:  Demos Health, 2013.   
10. 
Huffman, J.C., et al., A Positive Psychology Intervention for Patients with an Acute 
Coronary Syndrome: Treatment Development and Proof-of-Concept Trial. J Happiness 
Stud, 2016. 17(5): p. 1985-2006. 
11. 
Watson, D., L.A. Clark, and A. Tellegen, Development and validation of brief measures of 
positive and negative affect: the PANAS scales. J Pers Soc Psychol, 1988. 54(6): p. 1063-
70. 
12. 
Scheier, M.F., C.S. Carver, and M.W. Bridges, Distinguishing optimism from neuroticism 
(and trait anxiety, self-mastery, and self-esteem): a reevaluation of the Life Orientation 
Test. J Pers Soc Psychol, 1994. 67(6): p. 1063-78. 
13. 
Cella, D., et al., Neuro-QOL: brief measures of health-related quality of life for clinical 
research in neurology. Neurology, 2012. 78(23): p. 1860-7. 
14. 
Smith, B.W., et al., The brief resilience scale: assessing the ability to bounce back. Int J 
Behav Med, 2008. 15(3): p. 194-200. 
15. 
Huffman, J.C., et al., Development of a positive psychology intervention for patients with 
acute cardiovascular disease. Heart Int, 2011. 6(2): p. e14. 
 
 
 
 
 
 

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APPENDIX A 
 
Data Monitoring Committee / Data and Safety Monitoring Board 
Appendix 
 
 
 
• 
To be completed for studies monitored by Data Monitoring Committee (DMC) or Data and Safety 
Monitoring Board (DSMB) if a full DMC/DSMB charter is not available at the time of initial IRB 
review. 
• 
DMC/DSMB Charter and/or Roster can be submitted to the IRB later via Amendment, though these 
are not required.  
 
A Data Monitoring Committee (DMC) or Data and Safety Monitoring Board (DSMB) will be convened for 
safety monitoring of this research study.  The following characteristics describe the DMC/DSMB 
convened for this study (Check all that apply): 
 
☐ The DMC/DSMB is independent from the study team and study sponsor. 
 
☐ A process has been implemented to ensure absence of conflicts of interest by DMC/DSMB 
members. 
 
☐ The DMC/DSMB has the authority to intervene on study progress in the event of safety 
concerns, e.g., to suspend or terminate a study if new safety concerns have been identified or 
need to be investigated.   
 
☐ Describe number and types of (i.e., qualifications of) members: 
Click or tap here to enter text. 
 
☐  Describe planned frequency of meetings: 
Click or tap here to enter text. 
 
☐ DMC/DSMB reports with no findings (i.e., “continue without modifications”) will be submitted 
to the IRB at the time of Continuing Review. 
 
☐ DMC/DSMB reports with findings/modifications required will be submitted promptly (within 5 
business days/7 calendar days of becoming aware) to the IRB as an Other Event.