Efficacy and Mechanisms of Virtual Reality Treatment of Phantom Leg Pain

Study Overview
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Brief Summary
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After amputation of an arm or leg, up to 90% of subjects experience a phantom limb, a phenomenon characterized by persistent feelings of the missing limb. Many subjects with a phantom limb experience intense pain in the missing extremity that is often poorly responsive to medications or other interventions. The proposed work will contrast the efficacy of two virtual reality treatments for phantom limb pain: a 'Distractor' and an Active VR treatment. In the Distractor treatment, participants are engaged in a visually immersive virtual reality experience that does not require leg movements (REAL i-Series® immersive VR experience). In the Active VR treatment, subjects play a series of VR games using the virtual rendering of both legs.

Detailed Description
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Almost 2 million people in the US have had an amputation and up to 90% of people with limb amputation experience the persistent sensation of the missing extremity, a phenomenon known as a phantom limb (Weeks et al., 2010). Additionally, a significant proportion of individuals with a phantom limb - up to 85% in some studies - experience persistent and debilitating pain in the missing limb, a condition known as phantom limb pain (hereafter PLP). Although existing therapies provide pain relief in some cases, there is widespread agreement that current approaches fall short of bringing relief to most individuals with PLP (Weeks et al., 2010). The investigators recently completed a proof-of-concept study (Ambron et al., 2021) in which eight subjects with below knee amputations (BKA) underwent two virtual reality (VR) treatments for PLP. In an Active VR treatment, subjects played a variety of active games requiring leg movements while receiving high-quality visual feedback of the missing lower leg. Feedback about leg position was provided via an electromagnetic system using leg sensors (trackSTAR, Ascension Technologies Inc), and the program generated an image of the missing lower leg, visible as a first-person avatar. This treatment was contrasted with a Distractor treatment, in which participants were engaged in a visually immersive virtual reality experience that did not require leg movements (Cool!TM). Both treatments were associated with significant reductions in pain intensity, but the Active VR treatment was also associated with reductions in pain interference, depression, and anxiety. The specific aims of the current study are (i) to replicate our prior observations of efficacy of VR treatment in a larger sample of individuals with BKA; (ii) to test VR therapy in patients with above knee amputations; (iii) to compare the efficacy of Active VR treatment to Distractor VR treatment for PLP on measures of pain as well as psychological health and quality of life.

Official Title
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Efficacy and Mechanisms of Virtual Reality Treatment of Phantom Leg Pain: In-Person Treatment

Conditions
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Phantom Limb Pain

Intervention / Treatment
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* Behavioral: VR treatment for phantom limb pain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 100 years Capacity to provide Informed Consent Unilateral above or below knee amputation more than 3 months prior to enrollment Absence of cognitive impairment, operationally defined as a Montreal Cognitive Assessment score of 18 or greater Pain averaged over the preceding 1 month in the phantom limb rated as greater than 4 on a scale of 0-10. Exclusion Criteria: History of significant medical or neurological disorder such as stroke or moderate to severe traumatic brain injury (operationally defined as loss of consciousness for more than 30 minutes) History of significant or poorly controlled psychiatric disorders Current significant depression or anxiety as judged by the Hospital Anxiety and Depression Scale (HADS) (Zigmond & Snaith, 1983). Current abuse of alcohol or drugs, prescription or otherwise Nursing a child, pregnant, or intent to become pregnant during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Forty individuals with above (AKA) or below (BKA) knee amputation suffering from chronic phantom limb pain (PLP) will be recruited and will be quasi-randomly assigned to Active VR versus Distractor VR treatments in 50:50 ratio.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active VR treatment<br>Subjects assigned to the Active VR treatment will begin by selecting an avatar, with features such as gender and skin color that can be chosen according to preference. During treatment, they will participate in a variety of games and activities developed and used by our teams including Kick, Dog Food, Quest for Fire, Chess, Checkers, Sudoku, and surfing the internet. Subjects will have substantial flexibility to select games according to their interests but will be required to spend at least 30 minutes in each session in games that require forceful, large amplitude, movements of the amputated lower limb (e.g., Quest for Fire, Kick). Time spent and level of engagement as measured by movements of the avatar or, in the case of chess, checkers, solitaire, Sudoku, and internet surfing, the number of clicks produced with each leg will be recorded for each activity using custom software | Behavioral: VR treatment for phantom limb pain<br>* 8 twice-weekly interventions of 1 hour; baseline, pre-intervention; immediately after the end of the in intervention; 1 week after the end of the intervention; 8 weeks after the end of the intervention<br>|
| Experimental: Distractor VR treatment<br>Subjects assigned to the Distractor VR treatment will participate in REAL i-Series immersive VR experience (REAL system), which has been demonstrated to reduce pain in several studies but lacks the hypothesized active ingredients of our Active VR treatment (visual and auditory feedback of movement of an extrapolated amputated limb). Subjects will navigate through pleasant and relaxing VR environments; they will not see any rendering of their body and make no movements with their legs | Behavioral: VR treatment for phantom limb pain<br>* 8 twice-weekly interventions of 1 hour; baseline, pre-intervention; immediately after the end of the in intervention; 1 week after the end of the intervention; 8 weeks after the end of the intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pain intensity | Visual Analogue Scale of McGill Short Form Questionnaire (Melzack, 1987); 0 minimum score - 10 maximum score; higher scores indicate higher level of pain (worse outcome) | pre each intervention (8 sessions); immediately after each intervention (8 session); baseline, pre-intervention; immediately after the end of the intervention; 1 week after the end of the intervention; 8 weeks after the end of the intervention | 
| Changes in pain quality | McGill Short Form Questionnaire (Melzack, 1987): a series of 4-point scales assessing 15 characteristics of pain (e.g., throbbing, shooting, cramping, etc.). It generates separate scores for Sensory, Affective, and Total pain (maximum 78 points), and correlates strongly with the well-known long form of the questionnaire | baseline, pre-intervention; immediately after the end of the intervention; 1 week after the end of the intervention; 8 weeks after the end of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in average pain after the treatment | average pain intensity since the previous intervention on an 11-point numerical rating pain scale; (0 - minimum score/no pain; 10 maximum score/pain as bad as participants can imagine); higher scores indicate higher level of pain (worse outcome) | up to 4 weeks |