Comparing the Effectiveness of Education Versus Digital Cognitive Behavioral Therapy for Adults With Sickle Cell Disease: Protocol for the Cognitive Behavioral Therapy and Real-time Pain Management Intervention for Sickle Cell via Mobile Applications (CaRISMA) Study
Authors: Badawy Sherif M , Abebe Kaleab Z , Reichman Charlotte A , Checo Grace , Hamm Megan E , Stinson Jennifer , Lalloo Chitra , Carroll Patrick , Saraf Santosh L , Gordeuk Victor R , Desai Payal , Shah Nirmish , Liles Darla , Trimnell Cassandra , Jonassaint Charles R 
Published: March 2021

Background
Patients with sickle cell disease (SCD) experience significant medical and psychological stressors that affect their mental health, well-being, and disease outcomes. Digital cognitive behavioral therapy (CBT) has been used in other patient populations and has demonstrated clinical benefits. Although evidence-based, nonpharmacological interventions for pain management are widely used in other populations, these treatments have not been well studied in SCD. Currently, there are no adequately powered large-scale clinical trials to evaluate the effectiveness and dissemination potential of behavioral pain management for adults with SCD. Furthermore, some important details regarding behavioral therapies in SCD remain unclear—in particular, what works best for whom and when.

Objective
Our primary goal is to compare the effectiveness of two smartphone–delivered programs for reducing SCD pain symptoms: digital CBT versus pain and SCD education (Education). Our secondary goal is to assess whether baseline depression symptoms moderate the effect of interventions on pain outcomes. We hypothesize that digital CBT will confer greater benefits on pain outcomes and depressive symptoms at 6 months and a greater reduction in health care use (eg, opioid prescriptions or refills or acute care visits) over 12 months.

Methods
The CaRISMA (Cognitive Behavioral Therapy and Real-time Pain Management Intervention for Sickle Cell via Mobile Applications) study is a multisite comparative effectiveness trial funded by the Patient-Centered Outcomes Research Institute. CaRISMA is conducted at six clinical academic sites, in partnership with four community-based organizations. CaRISMA will evaluate the effectiveness of two 12-week health coach–supported digital health programs with a total of 350 participants in two groups: CBT (n=175) and Education (n=175). Participants will complete a series of questionnaires at baseline and at 3, 6, and 12 months. The primary outcome will be the change in pain interference between the study arms. We will also evaluate changes in pain intensity, depressive symptoms, other patient-reported outcomes, and health care use as secondary outcomes. We have 80% power to detect a difference of 0.37 SDs between study arms on 6-month changes in the outcomes with 15% expected attrition at 6 months. An exploratory analysis will examine whether baseline depression symptoms moderate the effect of the intervention on pain interference.

Results
This study will be conducted from March 2021 through February 2022, with results expected to be available in February 2023.

Conclusions
Patients with SCD experience significant disease burden, psychosocial stress, and impairment of their quality of life. CaRISMA proposes to leverage digital technology and overcome barriers to the routine use of behavioral treatments for pain and depressive symptoms in the treatment of adults with SCD. The study will provide data on the comparative effectiveness of digital CBT and Education approaches and evaluate the potential for implementing evidence-based behavioral interventions to manage SCD pain.

Trial Registration
ClinicalTrials.gov NCT04419168; https://clinicaltrials.gov/ct2/show/NCT04419168.

International Registered Report Identifier (IRRID)
PRR1-10.2196/29014