Virtual Reality for SCD VOC

Official title

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

Overview

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.

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.

Interventions

• 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 conditio
• 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.

Primary outcome measures

• Pain burden during the first 60 minutes after intervention start [Time frame: 60 minutes ± 10 minutes]

Secondary outcome measures (8)

• Pain at 120 minutes after intervention start (Durability of effect) [Time frame: 120 minutes]
• Participant-Reported Immersion Rating Immediately After Headset Session [Time frame: Immediately after headset session completion or early discontinuation]
• Participant-Reported Likelihood of Future Use Rating Immediately After Headset Session [Time frame: Immediately after headset session completion or early discontinuation]
• Opioid consumption during the first 60 minutes after intervention start [Time frame: 0 to 60 minutes after intervention start]
• Opioid consumption during the first 120 minutes after intervention start [Time frame: 0 to 120 minutes after intervention start]
• Headset session completion [Time frame: During the 45-minute headset session]
• Number of Headset Sessions With Any Headset-Related Adverse Symptom [Time frame: 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 [Time frame: From enrollment through 6 months after enrollment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Maryland Medical Center, Stoler Infusion Center — Baltimore

Publications

• 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. PMID 36752670
• 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. PMID 30362236
• 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. PMID 33136055
• 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. PMID 32720308
• 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. PMID 26596876
• 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. PMID 33062233
• 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. PMID 34401866
• 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. PMID 34544432

Identifiers

NCT: NCT07674277 · HP-00119171

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗