Efficacy and Mechanisms of Virtual Reality Treatment of Phantom Leg Pain

Phantom Limb Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296265
• Other study ID #: 2022-775.
• Status: Recruiting
• Phase: N/A
• Start date: May 10, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: April 2024
• Source: Albert Einstein Healthcare Network
• Contact: Laurel Buxbaum
• Phone: (215) 456-9901
• Email: Lbuxbaum[@]einstein.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Age 18 - 100 years

2. Capacity to provide Informed Consent

3. Unilateral above or below knee amputation more than 3 months prior to enrollment

4. Absence of cognitive impairment, operationally defined as a Montreal Cognitive Assessment score of 18 or greater

5. Pain averaged over the preceding 1 month in the phantom limb rated as greater than 4 on a scale of 0-10.

Exclusion Criteria:

1. 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)

2. History of significant or poorly controlled psychiatric disorders

3. Current significant depression or anxiety as judged by the Hospital Anxiety and Depression Scale (HADS) (Zigmond & Snaith, 1983).

4. Current abuse of alcohol or drugs, prescription or otherwise

5. Nursing a child, pregnant, or intent to become pregnant during the study

Related Conditions & MeSH terms

• Phantom Limb
• Phantom Limb Pain

Intervention

Behavioral:
• VR treatment for phantom limb pain
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

Locations

Country	Name	City	State
United States	Moss Rehabilitation Research Institute	Elkins Park	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Washington-Harborview Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Albert Einstein Healthcare Network	University of Pennsylvania, University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (12)

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: 10.1177/154596832110 — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in daily activities after the treatment	The Frenchay Activities Index (FAI) (Holbrook et al., 1983):1983): a scale measuring the physical function and daily activity that has excellent reliability in subjects with lower-limb amputation in predicting quality of life (Asono et al., 2008). 0 minimum score - 45 maximum score; higher scores indicate more daily activities (better outcome).	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
Other	Changes in quality of life after the treatment	The 12-Item Short Form Health Survey (SF-12) (Ware et al., 1996): a brief measure of quality of life and functional capacity that has been validated in patients with amputation and PLP (Padovani et al., 2015; Chen et al., 2012; Pape et al., 2010). 0 minimum score - 100 maximum score. Higher scores indicate lower physical and mental health (worse outcome).	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
Other	Changes in pain interference after the treatment	The Pain Interference Scale from the Brief Pain Inventory (BPI) (Cleeland & Ryan, 1994): this assesses the degree to which pain interferes with daily activities using a 0-10 numeric rating scale. 0 minimum score - 10 maximum score. Higher scores indicate higher pain interference (worse outcome).	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
Other	Changes in depression and anxiety as effect of the treatment	The Hospital Anxiety and Depression Scale (HADS) (Zigmond & Snaith, 1983):1983): the HADS is a 14- item measure assessing both depressive and anxiety symptoms. In addition to providing separate scores for anxiety and depression, the HADS also provides a measure of global negative affect. 0 minimum score - 42 maximum score. Higher scores indicate more depression and anxiety (worse outcome)	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
Other	Changes in the pain catastrophizing after the treatment	The 13-item Pain Catastrophizing Scale (Sullivan et al., 1995): this scale investigates pain catastrophizing, which has been highly associated with pain severity and disability after amputation (Hanley et al., 2004; Whyte & Carroll, 2004; Jensen et al., 2002). 0 minimum score -52; Higher scores indicate higher tendency to catastrophizing (worse outcome)	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
Other	Changes in insomnia after the treatment	Insomnia Severity Index (Bastien et al., 2001): this is a 7-point scale that measure insomnia, a symptom associated with PLP (Durmus et al., 2015). 0 minimum score - 28 maximum score; higher scores indicate more insomnia (worse outcome)	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
Other	Perception of VR system	Technology Acceptance Scale (Morris et al., 1997): this is a 7-point scale that measure level of acceptance of the VR system. 0 minimum score - 133 maximum score; higher scores indicate low level of acceptance (worse score)	baseline, pre-intervention
Other	Usability of each game	System Usability Scale (SUS) (Brooke, 1996); Scale measuring the usability of each game; minimum score 10 - maximum score 50. Higher scores indicate less usability (worse outcome).	immediately after the last intervention (session 8 of the intervention);
Other	Cybersickness	Simulator Sickness Questionnaire (Kennedy et al., 1993);	day 1, day 8
Other	Presence in VR	Brief Slater-Usoh-Steed Presence Questionnaire (Usoh et al., 2000; Slater et al., 1998; 1994). 7 minimum score - 42 maximum score. Higher scores indicate more presence in the VR (better outcome	day 1, day 8
Other	Changes in PL and PLP after the treatment	The Modified Limb Deficiency and Phantom Limb Questionnaire (Goller et al., 2013): this questionnaire assesses prosthesis type and usage and non-painful phantom limb experiences, including perceived position (e.g., telescoping) and ability to move the phantom. In addition to providing useful descriptive information, prosthesis use and telescoping will be used in the adaptive randomization algorithm to assign subjects to treatments.	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
Other	Treatment satisfaction	visual analogue scale that evaluates treatment satisfaction (Robinson et al., 2004; Smith et al., 2005); 0 minimum score - 10 maximum score; Higher scores indicate more treatment satisfaction (better outcome)	1 week after the end of the intervention
Primary	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
Primary	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	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