A Stress and Pain Self-management mHealth App for Adult Outpatients With Sickle Cell Disease: Protocol for a Randomized Controlled Study
Authors: Ezenwa Miriam O , Yao Yingwei , Mandernach Molly W , Fedele David A , Lucero Robert J , Corless Inge , Dyal Brenda W , Belkin Mary H , Rohatgi Abhinav , Wilkie Diana J 
Published: April 2022

Background
This paper describes the research protocol for a randomized controlled trial of a self-management intervention for adults diagnosed with sickle cell disease (SCD). People living with SCD experience lifelong recurrent episodes of acute and chronic pain, which are exacerbated by stress.

Objective
This study aims to decrease stress and improve SCD pain control with reduced opioid use through an intervention with self-management relaxation exercises, named You Cope, We Support (YCWS). Building on our previous findings from formative studies, this study is designed to test the efficacy of YCWS on stress intensity, pain intensity, and opioid use in adults with SCD.

Methods
A randomized controlled trial of the short-term (8 weeks) and long-term (6 months) effects of YCWS on stress, pain, and opioid use will be conducted with 170 adults with SCD. Patients will be randomized based on 1:1 ratio (stratified on pain intensity [≤5 or >5]) to be either in the experimental (self-monitoring of outcomes, alerts or reminders, and use of YCWS [relaxation and distraction exercises and support]) or control (self-monitoring of outcomes and alerts or reminders) group. Patients will be asked to report outcomes daily. During weeks 1 to 8, patients in both groups will receive system-generated alerts or reminders via phone call, text, or email to facilitate data entry (both groups) and intervention use support (experimental). If the participant does not enter data after 24 hours, the study support staff will contact them for data entry troubleshooting (both groups) and YCWS use (experimental). We will time stamp and track patients’ web-based activities to understand the study context and conduct exit interviews on the acceptability of system-generated and staff support. This study was approved by our institutional review board.

Results
This study was funded by the National Institute of Nursing Research of the National Institutes of Health in 2020. The study began in March 2021 and will be completed in June 2025. As of April 2022, we have enrolled 45.9% (78/170) of patients. We will analyze the data using mixed effects regression models (short term and long term) to account for the repeated measurements over time and use machine learning to construct and evaluate prediction models. Owing to the COVID-19 pandemic, the study was modified to allow for mail-in consent process, internet-based consent process via email or Zoom videoconference, devices delivered by FedEx, and training via Zoom videoconference.

Conclusions
We expect the intervention group to report reductions in pain intensity (primary outcome; 0-10 scale) and in stress intensity (0-10 scale) and opioid use (Wisepill event medication monitoring system), which are secondary outcomes. Our study will contribute to advancing the use of nonopioid therapy such as guided relaxation and distraction techniques for managing SCD pain.

Trial Registration
ClinicalTrials.gov NCT04484272; https://clinicaltrials.gov/ct2/show/NCT04484272

International Registered Report Identifier (IRRID)
PRR1-10.2196/33818