Virtual Reality for SCD VOC (RELIEVE-SCD)

Randomized EvaLuation of ImmErsive Virtual Experiences in Sickle Cell Disease (RELIEVE-SCD)

This pilot study will evaluate the feasibility, tolerability, and preliminary analgesic effect of headset-based virtual reality interventions for adults with sickle cell disease experiencing vaso-occlusive crisis treated in an infusion center. Participants will be enrolled during routine outpatient sickle cell clinic visits and may receive study interventions during future qualifying infusion center visits for vaso-occlusive pain. Using a randomized, two-period crossover design, each participant will be assigned to receive two of three headset-based conditions across separate visits: sham 2D headset control, passive immersive 3D virtual reality, or active immersive interactive 3D virtual reality. The primary outcome is pain burden during the first 60 minutes after intervention start, measured as area under the curve of 0-10 numeric rating scale pain scores. Secondary outcomes include feasibility of intervention delivery, headset tolerability, pain at 120 minutes, opioid use, and participant-reported immersion and acceptability.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Device: Sham 2D Headset Control; Device: Passive Immersive 3D Virtual Reality; Device: Active Immersive Interactive 3D Virtual Reality

Detailed Description

Vaso-occlusive crisis is a common and debilitating complication of sickle cell disease and is a frequent reason for treatment in acute care settings, including infusion centers and emergency departments. Opioid analgesics remain the mainstay of treatment for acute vaso-occlusive pain, but many patients continue to experience substantial pain, distress, and functional impairment despite standard therapy. Scalable, low-risk, non-pharmacologic adjuncts are needed to improve pain management during acute vaso-occlusive episodes.

Virtual reality is a promising non-pharmacologic approach to pain management that may reduce pain through immersive distraction, modulation of attention, and enhanced patient engagement. Prior studies suggest that virtual reality may reduce acute and chronic pain in some clinical settings, but the effect may vary by population and condition. Limited data are available regarding the use of virtual reality for acute vaso-occlusive pain in adults with sickle cell disease. This study is designed to evaluate the feasibility, tolerability, and preliminary analgesic effect of headset-based visual and audio interventions during infusion center treatment of vaso-occlusive crisis.

This is a randomized, controlled, two-period crossover pilot study using a balanced incomplete block design. Participants will be enrolled during routine outpatient sickle cell disease clinic visits when they are clinically stable and not experiencing an acute vaso-occlusive crisis. After enrollment, participants will be eligible to receive study interventions during future qualifying infusion center visits for vaso-occlusive pain occurring within the study follow-up window. At each qualifying visit, study staff will confirm continued eligibility, medical appropriateness, and the participant's willingness to proceed before delivering the assigned intervention.

Each participant will be randomized to receive two of three headset-based intervention conditions across two separate qualifying infusion center visits. The three conditions are: sham 2D headset control, consisting of non-interactive 2D visual content displayed on a fixed virtual screen with standardized audio; passive immersive 3D virtual reality, consisting of 360-degree or 3D immersive visual content with standardized audio without controller-based interaction; and active immersive interactive 3D virtual reality, consisting of immersive interactive virtual reality content with standardized audio and low-motion, seated controller-based interaction. Each intervention session is planned to last 45 minutes and will be delivered in addition to usual clinical care for vaso-occlusive crisis.

Randomization will assign each participant to one of three possible intervention pairs: sham 2D plus passive 3D virtual reality, sham 2D plus active interactive 3D virtual reality, or passive 3D virtual reality plus active interactive 3D virtual reality. Within each pair, the order of interventions will be randomized to balance period and sequence effects. Participants and study staff will not be blinded to the intervention condition because the interventions are perceptible; however, use of a headset-based control condition and standardized scripts is intended to reduce differences in attention and expectancy across conditions.

The primary outcome is pain burden during the first 60 minutes after intervention start, measured as area under the curve of 0-10 numeric rating scale pain scores. Pain scores will be collected before the intervention and at 15, 30, 45, and 60 minutes after intervention start. Secondary and exploratory outcomes include pain at 120 minutes, change in pain from baseline to 120 minutes, opioid administration summarized as morphine milligram equivalents, need for rescue analgesia, feasibility of intervention delivery, session completion, missing pain assessments, early discontinuation, headset-related symptoms, perceived immersion, and participant-reported likelihood of using the intervention again during future vaso-occlusive crisis treatment.

The study will enroll an anticipated convenience sample of approximately 20 to 25 participants based on the expected eligible infusion center population during the study period. The primary purpose of this pilot study is to estimate feasibility, tolerability, effect size, and variability to inform the design of a future larger efficacy trial.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Soowon Lee, MSPH; Phone Number: 254-400-4894; Email: Soowon.Lee@som.umaryland.edu
• Study Contact Backup: Name: Rose Corcoran; Phone Number: 2407439858; Email: rose.corcoran@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21230
      • University of Maryland Medical Center, Stoler Infusion Center
      • Contact: R. Gentry Wilkerson, MD; Phone Number: 410-328-4237; Email: GWilkerson@som.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (age ≥ 18 years) patients
• History of sickle cell disease
• Treatment plan by clinical care team includes the use of intravenous opioids to -treat acute pain.
• Receiving treatment from the Stoler Infusion center

Exclusion Criteria:

• Prior enrollment in this study
• Presenting with a chief complaint suggestive of a complicated crisis (such as concern for acute chest syndrome, splenic sequestration, hepatic sequestration, pulmonary embolism) as determined by the clinical care provider
• Not being treated with intravenous opioids for the vaso-occlusive crisis
• Patients who lack the capacity to provide informed consent
• Medical history of seizures or known intolerance to virtual reality devices
• In the opinion of the investigator and based on chart review and direct questioning of the patient, there are preexisting disabilities like vision and hearing defects that preclude the use of a head mounted virtual reality device.
• Known to be pregnant
• Incarcerated at the time of evaluation
• Over the age of 89 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sham 2D, then Passive 3D VR; Participants randomized to this sequence will receive the sham 2D headset control condition during the first qualifying vaso-occlusive crisis infusion center visit and the passive immersive 3D virtual reality condition during the second qualifying vaso-occlusive crisis infusion center visit. The sham 2D condition consists of non-interactive 2D visual content displayed on a fixed virtual screen with standardized audio. The passive immersive 3D virtual reality condition consists of 360-degree or 3D immersive visual content with standardized audio, allowing participants to look around without controller-based interaction.	Device: Sham 2D Headset Control; The sham 2D headset control condition consists of non-interactive two-dimensional visual content displayed on a fixed virtual screen using the Meta Quest headset platform. Standardized audio will be provided during the session. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. This condition is intended to serve as a headset-based control while maintaining similar attention and device exposure across study conditions.; Device: Passive Immersive 3D Virtual Reality; The passive immersive 3D virtual reality condition consists of 360-degree or three-dimensional immersive visual content delivered using the Meta Quest headset platform with standardized audio. Participants may look around within the virtual environment but will not interact with the content using controllers. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.
Experimental: Passive 3D VR → Sham 2D; Participants randomized to this sequence will receive the passive immersive 3D virtual reality condition during the first qualifying vaso-occlusive crisis infusion center visit and the sham 2D headset control condition during the second qualifying vaso-occlusive crisis infusion center visit. The passive immersive 3D virtual reality condition consists of 360-degree or 3D immersive visual content with standardized audio, allowing participants to look around without controller-based interaction. The sham 2D condition consists of non-interactive 2D visual content displayed on a fixed virtual screen with standardized audio.	Device: Sham 2D Headset Control; The sham 2D headset control condition consists of non-interactive two-dimensional visual content displayed on a fixed virtual screen using the Meta Quest headset platform. Standardized audio will be provided during the session. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. This condition is intended to serve as a headset-based control while maintaining similar attention and device exposure across study conditions.; Device: Passive Immersive 3D Virtual Reality; The passive immersive 3D virtual reality condition consists of 360-degree or three-dimensional immersive visual content delivered using the Meta Quest headset platform with standardized audio. Participants may look around within the virtual environment but will not interact with the content using controllers. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.
Experimental: Sham 2D → Active 3D VR; Participants randomized to this sequence will receive the sham 2D headset control condition during the first qualifying vaso-occlusive crisis infusion center visit and the active immersive interactive 3D virtual reality condition during the second qualifying vaso-occlusive crisis infusion center visit. The sham 2D condition consists of non-interactive 2D visual content displayed on a fixed virtual screen with standardized audio. The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content with standardized audio, using low-motion, seated modules with controller-based interaction.	Device: Sham 2D Headset Control; The sham 2D headset control condition consists of non-interactive two-dimensional visual content displayed on a fixed virtual screen using the Meta Quest headset platform. Standardized audio will be provided during the session. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. This condition is intended to serve as a headset-based control while maintaining similar attention and device exposure across study conditions.; Device: Active Immersive Interactive 3D Virtual Reality; The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content delivered using the Meta Quest headset platform with standardized audio. Participants will interact with the virtual environment using controllers while completing low-motion, seated modules. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.
Experimental: Active 3D VR → Sham 2D; Participants randomized to this sequence will receive the active immersive interactive 3D virtual reality condition during the first qualifying vaso-occlusive crisis infusion center visit and the sham 2D headset control condition during the second qualifying vaso-occlusive crisis infusion center visit. The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content with standardized audio, using low-motion, seated modules with controller-based interaction. The sham 2D condition consists of non-interactive 2D visual content displayed on a fixed virtual screen with standardized audio.	Device: Sham 2D Headset Control; The sham 2D headset control condition consists of non-interactive two-dimensional visual content displayed on a fixed virtual screen using the Meta Quest headset platform. Standardized audio will be provided during the session. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. This condition is intended to serve as a headset-based control while maintaining similar attention and device exposure across study conditions.; Device: Active Immersive Interactive 3D Virtual Reality; The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content delivered using the Meta Quest headset platform with standardized audio. Participants will interact with the virtual environment using controllers while completing low-motion, seated modules. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.
Experimental: Passive 3D VR → Active 3D VR; Participants randomized to this sequence will receive the passive immersive 3D virtual reality condition during the first qualifying vaso-occlusive crisis infusion center visit and the active immersive interactive 3D virtual reality condition during the second qualifying vaso-occlusive crisis infusion center visit. The passive immersive 3D virtual reality condition consists of 360-degree or 3D immersive visual content with standardized audio, allowing participants to look around without controller-based interaction. The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content with standardized audio, using low-motion, seated modules with controller-based interaction.	Device: Passive Immersive 3D Virtual Reality; The passive immersive 3D virtual reality condition consists of 360-degree or three-dimensional immersive visual content delivered using the Meta Quest headset platform with standardized audio. Participants may look around within the virtual environment but will not interact with the content using controllers. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.; Device: Active Immersive Interactive 3D Virtual Reality; The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content delivered using the Meta Quest headset platform with standardized audio. Participants will interact with the virtual environment using controllers while completing low-motion, seated modules. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.
Experimental: Active 3D VR → Passive 3D VR; Participants randomized to this sequence will receive the active immersive interactive 3D virtual reality condition during the first qualifying vaso-occlusive crisis infusion center visit and the passive immersive 3D virtual reality condition during the second qualifying vaso-occlusive crisis infusion center visit. The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content with standardized audio, using low-motion, seated modules with controller-based interaction. The passive immersive 3D virtual reality condition consists of 360-degree or 3D immersive visual content with standardized audio, allowing participants to look around without controller-based interaction.	Device: Passive Immersive 3D Virtual Reality; The passive immersive 3D virtual reality condition consists of 360-degree or three-dimensional immersive visual content delivered using the Meta Quest headset platform with standardized audio. Participants may look around within the virtual environment but will not interact with the content using controllers. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.; Device: Active Immersive Interactive 3D Virtual Reality; The active immersive interactive 3D virtual reality condition consists of immersive interactive virtual reality content delivered using the Meta Quest headset platform with standardized audio. Participants will interact with the virtual environment using controllers while completing low-motion, seated modules. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain burden during the first 60 minutes after intervention start	Pain burden will be measured as the area under the curve from 0 to 60 minutes of participant-reported pain scores using an 11-point Numeric Rating Scale, where 0 indicates no pain and 10 indicates the worst possible pain. Pain scores will be collected at baseline before intervention start and at 15, 30, 45, and 60 minutes after intervention start. Area under the curve will be calculated using the trapezoidal rule with actual recorded assessment times.	60 minutes ± 10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at 120 minutes after intervention start (Durability of effect)	Pain durability will be assessed using participant-reported pain scores at 120 minutes after intervention start and change in pain score from baseline to 120 minutes. Pain will be measured using an 11-point Numeric Rating Scale, where 0 indicates no pain and 10 indicates the worst possible pain. The 120-minute pain assessment will be considered valid if obtained within the prespecified window of 100 to 140 minutes after intervention start. If the participant leaves the infusion center before this window, study staff will attempt to obtain an end-of-encounter pain score with the time recorded.	120 minutes
Participant-Reported Immersion Rating Immediately After Headset Session	Perceived immersion will be assessed immediately after headset session completion or early discontinuation using a single participant-reported 0 to 10 rating scale in response to the question, "How immersive did the experience feel?" A score of 0 indicates not immersive at all, and a score of 10 indicates extremely immersive. Higher scores indicate greater perceived immersion.	Immediately after headset session completion or early discontinuation
Participant-Reported Likelihood of Future Use Rating Immediately After Headset Session	Acceptability will be assessed immediately after headset session completion or early discontinuation using a single participant-reported 0 to 10 rating scale in response to the question, "If available during future vaso-occlusive crisis treatment, how likely would you be to use this again?" A score of 0 indicates not at all likely, and a score of 10 indicates extremely likely. Higher scores indicate greater likelihood of future use.	Immediately after headset session completion or early discontinuation
Opioid consumption during the first 60 minutes after intervention start	Opioid analgesic administration will be recorded from the medical record and summarized as morphine milligram equivalents during the first 60 minutes after intervention start.	0 to 60 minutes after intervention start
Opioid consumption during the first 120 minutes after intervention start	Opioid analgesic administration will be recorded from the medical record and summarized as morphine milligram equivalents during the first 120 minutes after intervention start.	0 to 120 minutes after intervention start
Headset session completion	The proportion of initiated headset sessions completed without early discontinuation will be assessed for each intervention condition. Early discontinuation and the reason for discontinuation, including adverse symptoms, clinical interruption, or participant request, will be recorded.	During the 45-minute headset session
Number of Headset Sessions With Any Headset-Related Adverse Symptom	The number of initiated headset sessions in which the participant reports any headset-related adverse symptom will be recorded for each intervention condition. Headset-related adverse symptoms include nausea, dizziness, headache, eye strain, anxiety, panic, psychological distress, or other symptoms attributed to headset use. This outcome will be reported as a single count of sessions with one or more headset-related adverse symptoms.	From intervention start through immediately after headset session completion or early discontinuation, up to 45 minutes after intervention start
Completion of both assigned intervention periods	The proportion of enrolled participants who complete both assigned headset intervention periods within the study follow-up window will be assessed.	From enrollment through 6 months after enrollment

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Richard G Wilkerson, MD, Unversity of Maryland School of Medicine

Publications and helpful links

General Publications

• Williams H, Tanabe P. Sickle Cell Disease: A Review of Nonpharmacological Approaches for Pain. J Pain Symptom Manage. 2016 Feb;51(2):163-77. doi: 10.1016/j.jpainsymman.2015.10.017. Epub 2015 Nov 17.
• Agrawal AK, Robertson S, Litwin L, Tringale E, Treadwell M, Hoppe C, Marsh A. Virtual reality as complementary pain therapy in hospitalized patients with sickle cell disease. Pediatr Blood Cancer. 2019 Feb;66(2):e27525. doi: 10.1002/pbc.27525. Epub 2018 Oct 26.
• Smith V, Warty RR, Sursas JA, Payne O, Nair A, Krishnan S, da Silva Costa F, Wallace EM, Vollenhoven B. The Effectiveness of Virtual Reality in Managing Acute Pain and Anxiety for Medical Inpatients: Systematic Review. J Med Internet Res. 2020 Nov 2;22(11):e17980. doi: 10.2196/17980.
• Sundd P, Gladwin MT, Novelli EM. Pathophysiology of Sickle Cell Disease. Annu Rev Pathol. 2019 Jan 24;14:263-292. doi: 10.1146/annurev-pathmechdis-012418-012838. Epub 2018 Oct 17.
• Jang T, Poplawska M, Cimpeanu E, Mo G, Dutta D, Lim SH. Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events. J Transl Med. 2021 Sep 20;19(1):397. doi: 10.1186/s12967-021-03074-z.
• Duroseau Y, Beenhouwer D, Broder MS, Brown B, Brown T, Gibbs SN, Jackson K, Liang S, Malloy M, Romney ML, Shani D, Simon J, Yermilov I. Developing an emergency department order set to treat acute pain in sickle cell disease. J Am Coll Emerg Physicians Open. 2021 Aug 7;2(4):e12487. doi: 10.1002/emp2.12487. eCollection 2021 Aug.
• Osunkwo I, Manwani D, Kanter J. Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease. Ther Adv Hematol. 2020 Sep 29;11:2040620720955000. doi: 10.1177/2040620720955000. eCollection 2020.
• Chuan A, Zhou JJ, Hou RM, Stevens CJ, Bogdanovych A. Virtual reality for acute and chronic pain management in adult patients: a narrative review. Anaesthesia. 2021 May;76(5):695-704. doi: 10.1111/anae.15202. Epub 2020 Jul 27.
• Mercado SH. An outpatient pain plan and ED pain pathway for adults with sickle cell disease. JAAPA. 2023 Mar 1;36(3):20-23. doi: 10.1097/01.JAA.0000920956.33631.26.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 13, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: vaso-occlusive crisis; Sickle Cell Disease; virtual reality (VR)
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Vaso-Occlusive Crises
• Other Study ID Numbers: HP-00119171

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not plan on sharing any individual participant data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No