Mind-Body Approach to Improve Health-Related Quality of Life for People With Narcolepsy
Phase: NA
Conditions: Narcolepsy, Narcolepsy Without Cataplexy, Narcolepsy With Cataplexy
Sponsor: Northwestern University

Awareness and Self-Compassion Enhancing Narcolepsy Treatment (ASCENT) 
 
NCT04306952 
 
11/14/2018 

Protocol 
 
Overview of Research Plan   
The overall approach taken for this R34 follows recommendations for early stage treatment-
development activities aimed at establishing the parameters of the intervention and research 
protocols before conducting a full-scale randomized controlled trial (RCT). Building upon our 
preliminary data, this project focuses on treatment-development, recruitment, and assessment 
by conducting a feasibility trial to determine the optimal parameters for adapting and delivering 
an MBI for people with narcolepsy. The first phase of this project consists of preparatory 
activities, including completion of the study protocol and training of treatment providers. Phase II 
consists of a feasibility trial in which 60 individuals will be randomized to receive one of three 
MBI doses of varying length: 4-week MBI (short), 8-week MBI (standard), or 12-week MBI 
(extended).  All MBIs will feature similar content and structure and will be delivered in groups 
(n=4) using live videoconferencing.  
 
Phase I: Protocol refinement and training of MBI Providers 
The main goal of Phase I is to prepare for the feasibility trial. Preparatory activities include 
refining and completing the MBI protocols, developing a manual of operations, establishing a 
data and safety monitoring plan, and obtaining IRB approval. We have a preliminary outline of 
the three MBI doses that will be developed into a formal treatment manual that can be used for 
training and delivery.  
MBI Provider Training. The next step is to recruit and train at least 6 MBI providers. The 
purpose of this step is to determine the feasibility of recruiting MBI providers for a large-scale 
study and to evaluate the level of training needed for providers to work effectively with people 
with narcolepsy (see Specific Aim 1). We will select providers who have experience in delivering 
a traditional MBI, such as MBSR or MBCT, and who have a personal mindfulness meditation 
practice but do not have to be licensed clinicians (e.g., psychologist, social workers). This is 
consistent with the requirements for MBSR and MBCT, which should enhance the potential pool 
of providers. We will then provide training workshops, providing education on narcolepsy and 
the challenges that patients have described. We will also provide training on delivering each of 
the MBI doses (see C.8. and Table 3 below), emphasizing the adaptations from traditional MBIs 
and the application of mindfulness principles to working with symptoms of narcolepsy. Based on 
feedback from our focus groups (see C.2), we will educate providers on the symptoms of 
narcolepsy as well as the unique challenges that are common among people with narcolepsy 
(e.g., stigma, negative public perception, unpredictability of symptoms). We expect to conduct 
workshops via video-conferencing to enhance flexibility in recruiting MBI providers, but will also 
conduct these in-person for those who are in the local area. Each provider will be required to 
demonstrate competency in delivering the MBI protocols based on evaluation by the PI or Co-I. 
We will also gather input from MBI providers regarding the intervention and finalize the MBI 
protocols. The major milestones of this phase are to finalize the manual of operations for the 
study protocol, establish a treatment manual for each MBI dose, and train 6 MBI providers to 
deliver MBI.  
 
Phase II: Feasibility Trial  
Phase II consists of a feasibility trial to gather data on the feasibility, acceptability, and clinical 
impact of MBI.  Participants will be randomly assigned to receive one of three MBI doses (short, 
standard, or extended course) to determine the optimal parameters for length of the MBI 
program for people with narcolepsy. An important consideration at this stage is to optimize 
clinical impact and acceptability with cost-effectiveness as a secondary consideration in 
determining the optimal MBI dose. All MBIs will be delivered in small groups (n=4) using live 
videoconferencing. Recruitment and screening will begin upon completion of Phase I (month 6) 

and we anticipate running 5 cycles. Given the focus on optimization, we will conduct an interim 
review after completing Cycle 2 to evaluate the need for modifications to the MBI protocol or 
study protocol. We plan to complete the interventions and assessment in Year 3, between 
months 6 to 8, leaving the remaining time for data analysis, dissemination of results, and 
preparation of a U01 or R61/R33 application depending on the findings of this study.   
 
Short MBI (4-week). The short MBI consists of four weekly group sessions that are two hours 
each and follows the structure and format described above for each group and home meditation 
practice. Meta-analytic results of MBIs in lifestyle medicine trials have found that intervention 
effects are not dependent on the length of the MBI and that shorter-length MBIs (< 8 weeks) 
have demonstrated positive findings with effect sizes similar to MBI of 8 weeks or longer. 
Therefore, the rationale for testing the short MBI is to evaluate a low-dose (8 hours of contact) 
MBI that optimizes cost-effectiveness and minimizes patient burden. 
 
Standard MBI (8-week). The standard MBI consists of eight weekly group sessions that 
are approximately two hours each. Group sessions will follow the structure and format described 
above. The length of this package is based on the standard length of MBSR as an 8-week 
program. The rationale for testing the standard MBI is to provide a comparison to a dose (16 
hours of contact) that is most similar to the length of MBSR and has the fewest modifications, 
making it easier to train MBI providers.  
 
Extended MBI (12-week). The extended MBI consists of four weekly group sessions 
followed by four group sessions every other week over the course of 12 weeks. Each group 
session will be two hours and follows the contents and structure described above. The group 
sessions will be identical to the standard package except for the timing (every other week) of the 
last four sessions. In addition to the group sessions, the MBI provider will offer “office hours” in 
between the bi-weekly group sessions, where participants will be able to schedule individual 
sessions with the MBI provider to discuss questions and troubleshoot their mindfulness practice. 
The rationale for testing the extended MBI is to optimize acceptability and uptake based on our 
focus group data by allowing for a slower, extended pace of learning mindfulness practices with 
an opportunity to have individual discussions with the instructor (16 hours of contact + individual 
office hours). 
 
 
 
 

Data Analysis Plan 
 
Overall Approach and Power Considerations. The overall goal of this project is to work out the 
parameters of a mindfulness program that will be feasible and acceptable for people with 
narcolepsy. Following recommendations for pilot studies, this stage of testing focuses on 
evaluation of benchmarks and refinement of the intervention, recruitment methods, and 
assessment protocol. Formal hypothesis testing of outcomes and clinical endpoints will be 
conducted at a later stage, once the optimal MBI dose and delivery format is selected and 
refined. Since sex is not a biological variable of key interest in this study, we plan to conduct all 
analyses aggregated across sex. However, if patterns emerge to indicate that sex could 
influence the results, we will explore post-hoc analyses as needed (e.g., sex as a covariate). As 
suggested for pilot studies, our sample size was selected based on balancing the research 
priorities established in the specific aims with the pragmatics of recruitment and the resources 
allowed in the R34 funding mechanism. Data gathered on recruitment pace and effect size on 
clinical measures will be used to inform power considerations and the feasibility of conducting a 
large-scale trial in future studies. A summary of the analytic plan is described below. See 
Statistical Design and Power for details about specific analyses and the data management 
plan. 
   
Specific Aim 1. Determine the feasibility and acceptability of MBI using videoconferencing for 
the purpose of improving psychosocial functioning in people with narcolepsy. To carry out Aim 
1, we will evaluate the short, standard, and extended doses of MBI on the pre-determined 
benchmarks below to determine the feasibility and acceptability. 
• 
Benchmark 1 (feasibility of MBI providers): Recruit and train at least 6 qualified providers to 
deliver the MBI conditions (see section C.4. for details). No specific analyses are planned for 
this benchmark.     
• 
Benchmark 2 (acceptability of MBI doses): An average attendance ≥ 80% of sessions per 
MBI condition will be used as a benchmark for determining acceptability of the 
videoconference delivery of MBI and patient uptake of MBI. This benchmark corresponds to 
attendance of all sessions (4 out of 4) for the short MBI and 7 out of 8 sessions for the 
standard MBI. For extended MBI, participants must attend at least 6 out of 8 group sessions 
plus at least one optional individual session scheduled during provider “office hours” or 7 out 
of 8 group sessions if no individual sessions are scheduled.   
• 
Benchmark 3 (receipt of MBI targets): The benchmark for receipt of mindfulness and self-
compassion will be an increase from baseline to post-treatment in the SCS and FFMQ with 
an effect size in the moderate range or higher (Cohen’s d ≥ .5) per MBI dose. This 
benchmark will be used to evaluate the feasibility that people with narcolepsy are capable of 
acquiring self-compassion and mindfulness skills from the MBI and also provide estimations 
of the effect size for each MBI dose (4, 8, 12 weeks). Given that our conceptual model (see 
Figure 1) posits that self-compassion, mindful awareness, and mindful action are key 
putative mechanisms by which MBI improves HRQOL, this benchmark will provide an initial 
test of our conceptual model.  
• 
Benchmark 4 (feasibility of clinical impact): We will use a similar benchmark (d ≥ .5) to 
evaluate the clinical impact from baseline to post-treatment for each MBI dose on the 
PROMIS global health, depression, anxiety, and psychosocial illness impact measures.    
 
Secondary Considerations. In addition to these benchmarks, we will conduct other 
analyses as secondary considerations of acceptability and feasibility. We will examine the 
amount of meditation practice from the daily diaries (total minutes of practice and number of 
sessions) to assess enactment of mindfulness meditation outside of the sessions. We will 

conduct qualitative analyses from focus group data using thematic analysis to evaluate themes 
and patient feedback on each MBI dose. We will also conduct exit interviews with the MBI 
providers to gather input from the provider’s perspective as to the optimal MBI dose. In addition 
to evaluating effect sizes at post-treatment (Benchmark 3 & 4), we will also conduct linear mixed 
models to examine the trend of each MBI dose over time (A1 to A4) on SCS, FFMQ, and 
exploratory clinical measures (ESS, FOSQ, sleep/wake patterns from actigraphy and sleep 
diaries, neurocognitive assessment). These exploratory analyses will be used to supplement the 
evaluation of the effect sizes given the variation in time at post-treatment across MBI doses. We 
will also review adverse events and consider the potential harms as a factor in selecting the MBI 
condition (i.e., least AEs will be selected). Finally, we will consider the cost-effectiveness of 
each MBI dose (number of sessions, amount of face-to-face contact, amount of provider 
training). 
Selecting the optimal MBI dose. The major milestone of Specific Aim 1 is to select the 
optimal MBI condition using the parameters described above. We anticipate that each MBI dose 
will have a unique profile (e.g., short MBI will have high attendance but smaller effect size on 
SCS and FFMQ) and will select the MBI dose that is able to achieve the most benchmarks. If 
these benchmarks cannot determine a condition that is superior, we will use secondary 
considerations and cost-effectiveness (lowest-level of resources) to determine the optimal MBI 
dose. This MBI program will be used for further testing or optimization (see Future Directions).   
 
Specific Aim 2: Determine the feasibility of recruitment and assessment methods for MBI using 
videoconferencing. The purpose of Aim 2 is to evaluate the pace of recruitment and the 
feasibility of remote data collection using the assessment instruments proposed for conducting a 
future large-scale trial. We will use the following benchmarks to carry out Aim 2: 
• 
Benchmark 5 (recruitment feasibility): The benchmark for feasibility of recruitment will be 
enrollment of 12 participants who meet all eligibility criteria per 3-month cycle (or ≥ 4 
participants per month). The criteria for this benchmark is based on the minimum rate of 
recruitment needed to support randomization into groups of four for each of the MBI 
conditions. It will provide data to inform recruitment decisions, the method of randomization, 
and the number of sites needed for a large-scale study in the future. 
• 
Benchmark 6 (assessment feasibility): The benchmark for the assessment protocol is 
complete data for ≥ 80% of all participants (n=48 out of 60). Completion is defined as 
providing valid data from baseline (A1) through post-treatment for each MBI. This 
benchmark will inform the degree of missing data, the acceptability of the assessment 
protocol (e.g., neuropsychological assessment via videoconferencing), and the selection of 
instruments (e.g., reliability of collecting actigraphy data remotely).   
 
Secondary considerations. In addition to these benchmarks, we will evaluate the assessment 
instruments for inclusion in future studies by reviewing the effect size, costs, and patient 
feedback from focus groups for each instrument. For example, if there is evidence that some 
PROMIS domains selected for this study are not relevant we will not include these in future 
studies. We will also examine issues such as practice effects or fatigue to evaluate the validity 
and feasibility of conducting the neurocognitive battery using videoconferencing for people with 
narcolepsy. The major milestone of Aim 2 is to establish operational guidelines for effective 
recruitment methods and an assessment protocol that can be used to support a future large-
scale trial.