Sickle Cell DiseaseRELIEVE-SCDNCT07674277
Virtual Reality for SCD VOC
A study testing Passive Immersive 3D Virtual Reality and Active Immersive Interactive 3D Virtual Reality in people with Sickle Cell Disease, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
This randomized pilot study will evaluate the feasibility, tolerability, and preliminary analgesic effect of headset-based virtual reality (VR) interventions for adults with sickle cell disease (SCD) experiencing vaso-occlusive crisis (VOC) treated in an infusion center. Read more about this study
- Who is it for?
- Ages 18 to 88 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Passive Immersive 3D Virtual Reality and Active Immersive Interactive 3D Virtual Reality
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 88 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged 18 years or older.
- History of sickle cell disease.
- Treatment plan by the clinical care team includes intravenous opioids for acute pain.
- Receiving treatment through the Stoler Infusion Center.
Who cannot join
- Prior enrollment in this study.
- Presentation with a chief complaint suggestive of a complicated vaso-occlusive crisis, including concern for acute chest syndrome, splenic sequestration, hepatic sequestration, or pulmonary embolism, as determined by the treating clinician.
- Not receiving intravenous opioids for the vaso-occlusive crisis.
- Inability to provide informed consent.
- Medical history of seizures or known intolerance to virtual reality devices.
- Preexisting visual or hearing impairments that, in the investigator's judgment, preclude use of a head-mounted virtual reality device.
Show all 9Show fewer
- Known pregnancy.
- Incarceration at the time of evaluation.
- Age greater than 88 years.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Maryland Medical Center, Stoler Infusion Center
Baltimore, Maryland, 21230
R. Gentry Wilkerson, MD, 410-328-4237, GWilkerson@som.umaryland.edu
About this study
Official title: Randomized EvaLuation of ImmErsive Virtual Experiences in Sickle Cell Disease (RELIEVE-SCD)
This randomized pilot study will evaluate the feasibility, tolerability, and preliminary analgesic effect of headset-based virtual reality (VR) interventions for adults with sickle cell disease (SCD) experiencing vaso-occlusive crisis (VOC) treated in an infusion center. Up to 50 participants will be enrolled, provide informed consent, and undergo randomization during routine outpatient sickle cell clinic visits when they are clinically stable and not experiencing an acute VOC.
Using a randomized, two-period crossover design, each participant will be assigned to receive two of three headset-based interventions during separate qualifying infusion center visits for vaso-occlusive pain occurring within six months of enrollment: sham 2D headset control, passive immersive 3D VR, or active immersive interactive 3D VR. Each intervention will be delivered during a 45-minute session as an adjunct to usual clinical care.
The primary outcome is pain burden during the first 60 minutes after intervention start, measured as the 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 consumption, and participant-reported immersion and acceptability. Findings will inform the design of future trials evaluating VR as an adjunctive treatment for acute vaso-occlusive pain.
Read the detailed description
Vaso-occlusive crisis (VOC) is a common and debilitating complication of sickle cell disease (SCD) 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 (VR) 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 VR may reduce acute and chronic pain in some clinical settings, but its effect may vary by population and condition. Limited data are available regarding the use of VR for acute vaso-occlusive pain in adults with SCD. 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 VOC.
This is a randomized, controlled, two-period crossover pilot study using a balanced incomplete block design. Up to 50 participants will be enrolled during routine outpatient sickle cell disease clinic visits when they are clinically stable and not experiencing an acute VOC. Written informed consent and randomization will occur during these outpatient visits and will not occur during an acute VOC infusion center encounter. Following enrollment, participants will be eligible to receive study interventions during qualifying infusion center visits for vaso-occlusive pain occurring within six months of enrollment. At each qualifying visit, study staff will confirm continued eligibility, clinical 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: Non-interactive two-dimensional nature-related video content displayed on a fixed virtual screen with standardized audio.
- Passive immersive 3D VR: Immersive three-dimensional visual content delivered using the Nature Treks application with standardized audio, allowing participants to look around the virtual environment without controller-based interaction.
- Active immersive interactive 3D VR: Immersive interactive content delivered using the Nature Treks application with standardized audio, allowing participants to interact with the virtual environment using controllers while completing low-motion, seated activities.
All three intervention conditions will be delivered using the Meta Quest 2 headset platform. Each intervention session is planned to last 45 minutes and will be provided as an adjunct to usual clinical care for VOC. Participation will not alter clinical management, including opioid administration, rescue analgesia, fluid administration, monitoring, or disposition decisions.
Randomization will assign each participant to one of three possible intervention pairs: sham 2D plus passive immersive 3D VR, sham 2D plus active immersive interactive 3D VR, or passive immersive 3D VR plus active immersive interactive 3D VR. Within each pair, the order of interventions will be randomized to balance period and sequence effects, resulting in six possible intervention sequences. Participants and study staff will not be blinded to the intervention condition because the interventions are perceptible; however, the 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 the area under the curve of 0-10 numeric rating scale pain scores. Pain scores will be collected before intervention and at 15, 30, 45, and 60 minutes after intervention start. Secondary and exploratory outcomes include pain at approximately 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 adverse symptoms, perceived immersion, and participant-reported likelihood of using the intervention again during future VOC treatment.
The study will enroll a convenience sample of up to 50 participants based on the expected eligible infusion center population. Each participant may complete up to two intervention sessions during separate qualifying infusion center visits within six months of enrollment. The primary purpose of this pilot study is to estimate feasibility, tolerability, preliminary treatment effects, and variability to inform the design of a future larger efficacy trial.
- Conditions
- Sickle Cell Disease
- Being tested
- Sham 2D Headset Control, Passive Immersive 3D Virtual Reality, Active Immersive Interactive 3D Virtual Reality
- Keywords
- virtual reality (VR), Sickle Cell Disease, vaso-occlusive crisis
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sham 2D Headset ControlDevice
The sham 2D headset control condition consists of non-interactive, two-dimensional nature-related video content displayed on a fixed virtual screen using the Meta Quest 2 headset platform. The content will be presented through the YouTube application and will depict natural environments similar to those used in the immersive VR conditions. Standardized audio will accompany the visual content. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. This condition serves as a headset-based control to maintain similar device exposure and attention across intervention conditions while minimizing immersion and interactivity.
Passive Immersive 3D Virtual RealityDevice
The passive immersive 3D virtual reality condition consists of immersive three-dimensional visual content delivered through the Nature Treks application using the Meta Quest 2 headset platform. Participants will experience immersive natural environments with standardized audio and may look around 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. The intervention will be provided as an adjunct to usual clinical care.
Active Immersive Interactive 3D Virtual RealityDevice
The active immersive interactive 3D virtual reality condition consists of immersive, interactive three-dimensional content delivered through the Nature Treks application using the Meta Quest 2 headset platform. Participants will experience immersive natural environments with standardized audio and interact with the virtual environment using handheld controllers while completing low-motion, seated activities. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. The intervention will be provided as an adjunct to usual clinical care.
| Study group | Role | What they receive |
|---|---|---|
| Sham 2D, then Passive 3D VR | Experimental | 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. Receives: Device: Sham 2D Headset Control; Device: Passive Immersive 3D Virtual Reality |
| Passive 3D VR → Sham 2D | Experimental | 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. Receives: Device: Sham 2D Headset Control; Device: Passive Immersive 3D Virtual Reality |
| Sham 2D → Active 3D VR | Experimental | 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. Receives: Device: Sham 2D Headset Control; Device: Active Immersive Interactive 3D Virtual Reality |
| Active 3D VR → Sham 2D | Experimental | 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. Receives: Device: Sham 2D Headset Control; Device: Active Immersive Interactive 3D Virtual Reality |
| Passive 3D VR → Active 3D VR | Experimental | 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. Receives: Device: Passive Immersive 3D Virtual Reality; Device: Active Immersive Interactive 3D Virtual Reality |
| Active 3D VR → Passive 3D VR | Experimental | 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. Receives: Device: Passive Immersive 3D Virtual Reality; Device: Active Immersive Interactive 3D Virtual Reality |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 60 minutes ± 10 minutes
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From enrollment through 6 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2026
- Study start1 Nov 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will be randomized to receive two of three headset-based intervention conditions across two separate qualifying vaso-occlusive crisis infusion center visits using a balanced incomplete block crossover design. The three possible intervention pairs are sham 2D headset control plus passive immersive 3D virtual reality, sham 2D headset control plus active immersive interactive 3D virtual reality, or passive immersive 3D virtual reality plus active immersive interactive 3D virtual reality. Within each pair, the order of the two assigned interventions will be randomized.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Gentry Wilkerson, University of Maryland, Baltimore
- Investigators
- Richard G Wilkerson, MD, Principal investigator, Unversity of Maryland School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07674277
- Sponsor's protocol ID
- HP-00119171
- Acronym
- RELIEVE-SCD
- Status last verified
- Oct 2026
- First submitted
- 13 Jun 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: We do not plan on sharing any individual participant data with other researchers
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.
PubMed 36752670Agrawal 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.
PubMed 30362236Smith 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.
PubMed 33136055Chuan 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.
PubMed 32720308Williams 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.
PubMed 26596876Osunkwo 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.
PubMed 33062233Duroseau 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.
PubMed 34401866Jang 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.
PubMed 34544432Sundd 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.
PubMed 30332562
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized EvaLuation of ImmErsive Virtual Experiences in Sickle Cell Disease (RELIEVE-SCD)
- ClinicalTrials.gov ID
- NCT07674277
- Acronym / sponsor ID
- RELIEVE-SCD / HP-00119171
- Conditions
- Sickle Cell Disease
- Keywords
- virtual reality (VR), Sickle Cell Disease, vaso-occlusive crisis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 29 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized pilot study will evaluate the feasibility, tolerability, and preliminary analgesic effect of headset-based virtual reality (VR) interventions for adults with sickle cell disease (SCD) experiencing vaso-occlusive crisis (VOC) treated in an infusion center. Up to 50 participants will be enrolled, provide informed consent, and undergo randomization during routine outpatient sickle cell clinic visits when they are clinically stable and not experiencing an acute VOC.
Using a randomized, two-period crossover design, each participant will be assigned to receive two of three headset-based interventions during separate qualifying infusion center visits for vaso-occlusive pain occurring within six months of enrollment: sham 2D headset control, passive immersive 3D VR, or active immersive interactive 3D VR. Each intervention will be delivered during a 45-minute session as an adjunct to usual clinical care.
The primary outcome is pain burden during the first 60 minutes after intervention start, measured as the 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 consumption, and participant-reported immersion and acceptability. Findings will inform the design of future trials evaluating VR as an adjunctive treatment for acute vaso-occlusive pain.
Detailed description
Vaso-occlusive crisis (VOC) is a common and debilitating complication of sickle cell disease (SCD) 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 (VR) 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 VR may reduce acute and chronic pain in some clinical settings, but its effect may vary by population and condition. Limited data are available regarding the use of VR for acute vaso-occlusive pain in adults with SCD. 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 VOC.
This is a randomized, controlled, two-period crossover pilot study using a balanced incomplete block design. Up to 50 participants will be enrolled during routine outpatient sickle cell disease clinic visits when they are clinically stable and not experiencing an acute VOC. Written informed consent and randomization will occur during these outpatient visits and will not occur during an acute VOC infusion center encounter. Following enrollment, participants will be eligible to receive study interventions during qualifying infusion center visits for vaso-occlusive pain occurring within six months of enrollment. At each qualifying visit, study staff will confirm continued eligibility, clinical 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: Non-interactive two-dimensional nature-related video content displayed on a fixed virtual screen with standardized audio.
- Passive immersive 3D VR: Immersive three-dimensional visual content delivered using the Nature Treks application with standardized audio, allowing participants to look around the virtual environment without controller-based interaction.
- Active immersive interactive 3D VR: Immersive interactive content delivered using the Nature Treks application with standardized audio, allowing participants to interact with the virtual environment using controllers while completing low-motion, seated activities.
All three intervention conditions will be delivered using the Meta Quest 2 headset platform. Each intervention session is planned to last 45 minutes and will be provided as an adjunct to usual clinical care for VOC. Participation will not alter clinical management, including opioid administration, rescue analgesia, fluid administration, monitoring, or disposition decisions.
Randomization will assign each participant to one of three possible intervention pairs: sham 2D plus passive immersive 3D VR, sham 2D plus active immersive interactive 3D VR, or passive immersive 3D VR plus active immersive interactive 3D VR. Within each pair, the order of interventions will be randomized to balance period and sequence effects, resulting in six possible intervention sequences. Participants and study staff will not be blinded to the intervention condition because the interventions are perceptible; however, the 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 the area under the curve of 0-10 numeric rating scale pain scores. Pain scores will be collected before intervention and at 15, 30, 45, and 60 minutes after intervention start. Secondary and exploratory outcomes include pain at approximately 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 adverse symptoms, perceived immersion, and participant-reported likelihood of using the intervention again during future VOC treatment.
The study will enroll a convenience sample of up to 50 participants based on the expected eligible infusion center population. Each participant may complete up to two intervention sessions during separate qualifying infusion center visits within six months of enrollment. The primary purpose of this pilot study is to estimate feasibility, tolerability, preliminary treatment effects, and variability to inform the design of a future larger efficacy trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Participants will be randomized to receive two of three headset-based intervention conditions across two separate qualifying vaso-occlusive crisis infusion center visits using a balanced incomplete block crossover design. The three possible intervention pairs are sham 2D headset control plus passive immersive 3D virtual reality, sham 2D headset control plus active immersive interactive 3D virtual reality, or passive immersive 3D virtual reality plus active immersive interactive 3D virtual reality. Within each pair, the order of the two assigned interventions will be randomized.
| Arm | Type | Receives |
|---|---|---|
| Sham 2D, then Passive 3D VR | Experimental | Device: Sham 2D Headset Control, Device: Passive Immersive 3D Virtual RealityParticipants 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. |
| Passive 3D VR → Sham 2D | Experimental | Device: Sham 2D Headset Control, Device: Passive Immersive 3D Virtual RealityParticipants 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. |
| Sham 2D → Active 3D VR | Experimental | Device: Sham 2D Headset Control, Device: Active Immersive Interactive 3D Virtual RealityParticipants 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. |
| Active 3D VR → Sham 2D | Experimental | Device: Sham 2D Headset Control, Device: Active Immersive Interactive 3D Virtual RealityParticipants 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. |
| Passive 3D VR → Active 3D VR | Experimental | Device: Passive Immersive 3D Virtual Reality, Device: Active Immersive Interactive 3D Virtual RealityParticipants 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. |
| Active 3D VR → Passive 3D VR | Experimental | Device: Passive Immersive 3D Virtual Reality, Device: Active Immersive Interactive 3D Virtual RealityParticipants 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. |
Who may qualify
- Ages
- 18 to 88 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients aged 18 years or older.
- History of sickle cell disease.
- Treatment plan by the clinical care team includes intravenous opioids for acute pain.
- Receiving treatment through the Stoler Infusion Center.
Key exclusion criteria (9 listed)
- Prior enrollment in this study.
- Presentation with a chief complaint suggestive of a complicated vaso-occlusive crisis, including concern for acute chest syndrome, splenic sequestration, hepatic sequestration, or pulmonary embolism, as determined by the treating clinician.
- Not receiving intravenous opioids for the vaso-occlusive crisis.
- Inability to provide informed consent.
- Medical history of seizures or known intolerance to virtual reality devices.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sham 2D Headset ControlThe sham 2D headset control condition consists of non-interactive, two-dimensional nature-related video content displayed on a fixed virtual screen using the Meta Quest 2 headset platform. The content will be presented through the YouTube application and will depict natural environments similar to those used in the immersive VR conditions. Standardized audio will accompany the visual content. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. This condition serves as a headset-based control to maintain similar device exposure and attention across intervention conditions while minimizing immersion and interactivity. | Device | Active 3D VR → Sham 2D, Passive 3D VR → Sham 2D, Sham 2D → Active 3D VR, Sham 2D, then Passive 3D VR |
| Passive Immersive 3D Virtual RealityThe passive immersive 3D virtual reality condition consists of immersive three-dimensional visual content delivered through the Nature Treks application using the Meta Quest 2 headset platform. Participants will experience immersive natural environments with standardized audio and may look around 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. The intervention will be provided as an adjunct to usual clinical care. | Device | Active 3D VR → Passive 3D VR, Passive 3D VR → Active 3D VR, Passive 3D VR → Sham 2D, Sham 2D, then Passive 3D VR |
| Active Immersive Interactive 3D Virtual RealityThe active immersive interactive 3D virtual reality condition consists of immersive, interactive three-dimensional content delivered through the Nature Treks application using the Meta Quest 2 headset platform. Participants will experience immersive natural environments with standardized audio and interact with the virtual environment using handheld controllers while completing low-motion, seated activities. Participants will wear the headset for a planned 45-minute session during a qualifying vaso-occlusive crisis infusion center visit. The intervention will be provided as an adjunct to usual clinical care. | Device | Active 3D VR → Passive 3D VR, Active 3D VR → Sham 2D, Passive 3D VR → Active 3D VR, Sham 2D → Active 3D VR |
Primary outcome
Pain burden during the first 60 minutes after intervention start
Time frame: 60 minutes ± 10 minutes
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.
8 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Background: PubMed 36752670Mercado 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.
- Background: PubMed 30362236Agrawal 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.
- Background: PubMed 33136055Smith 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.
- Background: PubMed 32720308Chuan 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.
- Background: PubMed 26596876Williams 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.
- Background: PubMed 33062233Osunkwo 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.
- Background: PubMed 34401866Duroseau 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.
- Background: PubMed 34544432Jang 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.
- Background: PubMed 30332562Sundd 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.
- Individual participant dataSharing planned: No. We do not plan on sharing any individual participant data with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Richard G Wilkerson, MD principal investigator
Unversity of Maryland School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Passive Immersive 3D Virtual Reality and Active Immersive Interactive 3D Virtual Reality in people with Sickle Cell Disease, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Soowon Lee, MSPH (254-400-4894, Soowon.Lee@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain burden during the first 60 minutes after intervention start (time frame: 60 minutes ± 10 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07674277, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.