Efficacy and Mechanisms of Virtual Reality Treatment of Phantom Leg Pain

NCT05296265 | Completed Results DMC

• 2 other identifiers: 2022-775.5R01HD104158-05
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Phantom Limb Pain

Outcome Measures

Primary Outcomes (2)

• Changes in Pain Intensity

  Visual Analogue Scale (VAS) of McGill Short Form Questionnaire (Melzack, 1987); 0 minimum score - 10 maximum score; higher scores indicate higher level of pain (worse outcome)

  Baseline versus immediately post-intervention at 4 weeks.

• Changes in Pain Quality

  McGill Short Form Questionnaire (Melzack, 1987): a series of 4-point scales (0 none - 3 severe) assessing the intensity of 15 qualitative characteristics of pain (e.g., throbbing, shooting, cramping, etc.), where higher scores are worse (more severe). For every participant we computed the total pain score (maximum 45 points indicating severe pain). Then, we computed the difference in the total scores between time points (e.g. post treatment vs baseline). Therefore, negative scores indicate improvement in pain qualitative characteristics.

  Baseline versus immediately post-intervention at 4 weeks.

Secondary Outcomes (1)

• Changes in Average Pain

  1st treatment versus 8th treatment (4 weeks)

Other Outcomes (12)

• Changes in Daily Activities

  Baseline versus immediately post-intervention at 4 weeks.

• Changes in Quality of Life

  Baseline versus immediately post-intervention at 4 weeks.

• Changes in Pain Interference

  Baseline versus immediately post-intervention at 4 weeks

Study Arms (2)

Active VR treatment

EXPERIMENTAL

Subjects assigned to the Active VR treatment began by selecting an avatar, with features such as gender and skin color that could be chosen according to preference. During treatment, they participated 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 had substantial flexibility to select games according to their interests but were required to spend at least 30 minutes in each session in games that required forceful, large-amplitude movements of the amputated lower limb (e.g., Quest for Fire, Kick).

Behavioral: VR treatment for phantom limb pain

Distractor VR treatment

EXPERIMENTAL

Subjects assigned to the Distractor VR treatment participated in the REAL i-Series immersive VR experience (REAL system), which had been demonstrated to reduce pain in several studies but lacked the hypothesized "active ingredients" of our Active VR treatment (visual and auditory feedback of movement of an extrapolated amputated limb). Subjects navigated through pleasant and relaxing VR environments; they did not see any rendering of their body and made no movements with their legs.

Behavioral: VR treatment for phantom limb pain

Interventions

VR treatment for phantom limb pain BEHAVIORAL

8 twice-weekly interventions of virtual reality treatment focused on reducing phantom limb pain.

Active VR treatment; Distractor VR treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Albert Einstein Healthcare Network: lead
• University of Pennsylvania: collaborator
• University of Washington: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

Moss Rehabilitation Research Institute

Elkins Park, Pennsylvania, 19027, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington-Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (12)

• Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-197. doi: 10.1016/0304-3959(87)91074-8.

  PMID: 3670870 BACKGROUND

• Holbrook M, Skilbeck CE. An activities index for use with stroke patients. Age Ageing. 1983 May;12(2):166-70. doi: 10.1093/ageing/12.2.166.

  PMID: 6869117 BACKGROUND

• Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003.

  PMID: 8628042 BACKGROUND

• Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.

  PMID: 8080219 BACKGROUND

• Goller AI, Richards K, Novak S, Ward J. Mirror-touch synaesthesia in the phantom limbs of amputees. Cortex. 2013 Jan;49(1):243-51. doi: 10.1016/j.cortex.2011.05.002. Epub 2011 Jun 22.

  PMID: 22981809 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

• Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4.

  PMID: 11438246 BACKGROUND

• Slater M, Steed A, McCarthy J, Maringelli F. The influence of body movement on subjective presence in virtual environments. Hum Factors. 1998 Sep;40(3):469-77. doi: 10.1518/001872098779591368.

  PMID: 9849105 BACKGROUND

• Suresh K. An overview of randomization techniques: An unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011 Jan;4(1):8-11. doi: 10.4103/0974-1208.82352.

  PMID: 21772732 BACKGROUND

• Ambron E, Buxbaum LJ, Miller A, Stoll H, Kuchenbecker KJ, Coslett HB. Virtual Reality Treatment Displaying the Missing Leg Improves Phantom Limb Pain: A Small Clinical Trial. Neurorehabil Neural Repair. 2021 Dec;35(12):1100-1111. doi: 10.1177/15459683211054164. Epub 2021 Oct 27.

  PMID: 34704486 BACKGROUND

• Robinson LR, Czerniecki JM, Ehde DM, Edwards WT, Judish DA, Goldberg ML, Campbell KM, Smith DG, Jensen MP. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. Arch Phys Med Rehabil. 2004 Jan;85(1):1-6. doi: 10.1016/s0003-9993(03)00476-3.

  PMID: 14970960 BACKGROUND

• Smith DG, Ehde DM, Hanley MA, Campbell KM, Jensen MP, Hoffman AJ, Awan AB, Czerniecki JM, Robinson LR. Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. J Rehabil Res Dev. 2005 Sep-Oct;42(5):645-54. doi: 10.1682/jrrd.2005.05.0082.

  PMID: 16586190 BACKGROUND

MeSH Terms

Conditions

Phantom Limb

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain

Limitations and Caveats

There are no limitations to determine the effect of the intervention

Results Point of Contact

• Title: Elisabetta Ambron
• Organization: University of Pennsylvania

eli.ambron@gmail.com

4842805561

Study Officials

• Laurel Buxbaum, PsyD

  Albert Einstein Healthcare Netork

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Institute Scientist, Moss Rehabilitation Research Institute

Model Details: Forty individuals with above (AKA) or below (BKA) knee amputation suffering from chronic phantom limb pain (PLP) were recruited and quasi-randomly assigned to Active VR versus Distractor VR treatments.

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 25, 2022
• Study Start: May 10, 2022
• Primary Completion: March 16, 2025
• Study Completion: April 6, 2025
• Last Updated: September 30, 2026
• Results First Posted: September 9, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a sound rationale.

Locations

US (3)