Clinical trial NCT05247827: The Effects of Targeted Phantom Motor Execution on Phantom Limb Control
Official title: The Effects of Targeted Phantom Motor Execution, Prosthetic Embodiment, and Surgical Closure on Phantom Limb Control, and Physical Function in People With Unilateral (Single) Transtibial (Below-the-knee) Amputation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Phantom Limb
Motor Activity
Amputation Stump
Amputation
Keywords: Prosthetic embodiment
Surgical closure
Phantom limb control
Physical function
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
Collaborators: name: University of Manitoba
First posted: 2022-02-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lower limb amputations account for more than 85% of all amputations. In Canada, it has been reported that transtibial amputation (TTA) is the most common level of amputation. Many people with limb amputation have awareness and feel that their missing limb still exists (phantom limb), with perceptions of sensation or pain, and the ability to move the limb with or without intention. Phantom limb sensation (PLS) is defined as all non-painful somatic sensations (e.g. sense of the limb position, touch, pressure, warmth or cold, or movement) in the missing part of the limb. The incidence of PLS is about 60% in adults after 17 months. In addition to PLS, 60-70% of people with amputation experience phantom limb pain (PLP), an intense chronic pain perception in their phantom limb, in the first year after amputation. Although PLP is well known to decrease the quality of life and lessen function, little is known about PLS and phantom limb control (PLC), the ability to intentionally move or control movements of the phantom limb. Enhancing PLS and PLC especially in the immediate months after amputation, could decrease painful perception, facilitate prosthetic control, and improve the function of people with amputations. Keeping this therapeutic and rehabilitative significance in mind, it is hypothesized that a targeted program of phantom motor execution, designed to address phantom limb awareness (PLA), the general knowledge of the presence or existence of the missing limb as one's own, could be associated with improving PLC in people with TTA. Furthermore, prosthetic embodiment, the sense that the prosthesis is accepted as a part of the body with the same functional abilities, may play a role in PLC. Investigating the association of PLC, as one of the phantom phenomena (i.e. PLA, PLS, PLP, and PLC), with surgical, clinical, and demographic characteristics of people with TTA will provide better insight into how phantom phenomena develop. The association of PLC with physical function has significant clinical importance that has never been investigated in people with TTA.

Detailed description: This research explores testing of the following hypotheses with four independent but interrelated studies:

Study #1:

In people with TTA, post-amputation exercises focus on strength, balance, flexibility, and endurance training of the residual limb and intact limb muscles. Phantom limb motor execution, the active movement of the amputated body part, is not usually encouraged until a patient complains of PLP with the hypothesis that this intervention could re-organize the motor cortex to pre-amputation neural network and function. It was shown that phantom motor execution promoted by mirror therapy, virtual reality, and augmented reality could be used as a non-invasive therapy to relieve PLP in people with limb amputation. However, it is not clear if training with phantom motor execution improves peripheral control over the phantom limb. Therefore, this study explores the effects of a targeted phantom motor execution program on PLC in people with unilateral TTA.

Specific aim: To determine if targeted phantom motor execution improves control of the phantom limb, as measured by EMG patterning, in people with unilateral TTA.

Research hypothesis: People with unilateral TTA will improve control of their phantom limb after completion of a targeted phantom motor execution program.

Study #2:

Prosthetic embodiment is a sense that people with limb amputation feel that their prosthesis is integrated into their body and acts like their limb before amputation. It has been shown that higher prosthesis embodiment is associated with less PLP with the thought that it reverses brain plasticity after amputation. It is not clear whether prosthetic embodiment has any effect on PLC. This study explores the potential association between prosthetic embodiment and PLC in people with unilateral TTA.

Specific aim: To determine if there is a correlation between prosthetic embodiment, as measured by the self-reported TAPES-R and PEmbS-LLA questionnaires, and PLC (self-report), in people with unilateral TTA.

Research hypothesis: There is a strong positive association between prosthetic embodiment and PLC in people with unilateral TTA.

Study #3:

Surgical closure of the dissected muscles of the residual limb has been shown to impact PLP in people with limb amputation. The two most common surgical closure techniques are myodesis connection of the dissected muscles to bone/periosteum, and myoplasty, the connection of the dissected muscles to antagonist muscles. Residual limb muscles activity and PLA could be influenced by the distal closure of the dissected muscles. However, there is a scarcity of evidence on how surgical closure impacts the PLC. This study explores the association of surgical closure with PLC by measuring the symmetry of EMG muscle activity between the amputated and intact sides in people with unilateral TTA.

Specific aim: To determine if PLC, as measured by the symmetry of EMG muscle activity, is influenced by the surgical closure technique of the dissected muscles.

Research hypothesis: People who undergo unilateral TTA and myodesis surgical closure of the dissected muscles will have better PLC, as measured by the symmetry of EMG muscle activity, than those who undergo unilateral TTA and myoplasty surgical closure of the dissected muscles.

Study #4:

The previous three studies investigate the effects of the targeted phantom motor execution, prosthetic embodiment, and surgical closure on PLC. In the literature, it has been shown that improvement of PLC has been correlated with decreased PLP, and reduced PLP is associated with better function in people with limb amputation. However, it is not clear whether PLC has an association with physical function in people with TTA.

Specific aim: To determine if there is a correlation between PLC (self-report) and physical function, as measured by the four-square step test (FSST), in people with unilateral TTA.

Research hypothesis: There is a strong positive association between PLC and physical function in people with unilateral TTA.

Eligibility criteria: Inclusion Criteria:

1. 18 years of age or older
2. Amputation surgery in Manitoba
3. Amputation surgery at least 6 months ago
4. Unilateral TTA
5. Existence of mature and wound-free residual limb
6. Experience of walking with a prosthesis for at least five months
7. Having contralateral healthy foot with no wounds, ulcers, abrasions, or loss of toes
8. Ability to walk independently for two minutes with/without an assistive device
9. Presence of PLA
10. Ability to read, write, and understand instructions and questionnaires in English
11. Have the dexterity to use a computer, tablet, or smartphone and the ability to communicate through Zoom application.

Exclusion Criteria:

1. Existence of psychological or psychiatric conditions (e.g. depression or anxiety) that negatively impact daily life
2. Addiction to alcohol or drug
3. Any medical condition that might conceivably alter how a person perceives the body or their ability to execute movements
4. Inability to move the intact limb at the foot and ankle joints
5. Fluctuating doses of pain suppressing medications in the previous month
6. Receiving formal training on exercising phantom limb
7. Existence of severe pain that limits activity
8. Undergoing prosthetic adjustments (e.g. in socket fit, components, alignment) in the past five months or plan to have prosthetic adjustments over the study period

Primary outcomes:
measure: Phantom limb control as measured by EMG patterning
timeFrame: 1 year (March 2022 - March 2023)
measure: Prosthetic embodiment as measured by "Trinity Amputation and Prosthesis Experience Scales-Revised (TAPES-R)"
timeFrame: 1 year (March 2022 - March 2023)
measure: Prosthetic embodiment as measured by "Prosthesis Embodiment Scale for Lower Limb Amputees (PEmbS-LLA)"
timeFrame: 1 year (March 2022 - March 2023)
measure: Time score for four-square step test (s)
timeFrame: 1 year (March 2022 - March 2023)
Secondary outcomes:
measure: Amplitude of electromyography (EMG) of the agonist and antagonist muscles's activity
timeFrame: 1 year (March 2022 - March 2023)
measure: Frequency of electromyography (EMG) of the agonist and antagonist muscles's activity
timeFrame: 1 year (March 2022 - March 2023)
measure: Index of electromyography (EMG) co-activation of the agonist and antagonist muscles
timeFrame: 1 year (March 2022 - March 2023)
measure: Foot plantar load (N)
timeFrame: 1 year (March 2022 - March 2023)
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Winnipeg Prosthetics and Orthotics (WinPO) Clinic
state: Manitoba
Study officials:
affiliation: University of Saskatchewan
name: Audrey Zucker-Levin, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bekrater-Bodmann R, Reinhard I, Diers M, Fuchs X, Flor H. Relationship of prosthesis ownership and phantom limb pain: results of a survey in 2383 limb amputees. Pain. 2021 Feb 1;162(2):630-640. doi: 10.1097/j.pain.0000000000002063.
citation: Brodie EE, Whyte A, Niven CA. Analgesia through the looking-glass? A randomized controlled trial investigating the effect of viewing a 'virtual' limb upon phantom limb pain, sensation and movement. Eur J Pain. 2007 May;11(4):428-36. doi: 10.1016/j.ejpain.2006.06.002. Epub 2006 Jul 20.
citation: Dijkstra PU, Geertzen JH, Stewart R, van der Schans CP. Phantom pain and risk factors: a multivariate analysis. J Pain Symptom Manage. 2002 Dec;24(6):578-85. doi: 10.1016/s0885-3924(02)00538-9.
citation: Flor H, Nikolajsen L, Staehelin Jensen T. Phantom limb pain: a case of maladaptive CNS plasticity? Nat Rev Neurosci. 2006 Nov;7(11):873-81. doi: 10.1038/nrn1991.
citation: Geertzen JHB, van der Schans SM, Jutte PC, Kraeima J, Otten E, Dekker R. Myodesis or myoplasty in trans-femoral amputations. What is the best option? An explorative study. Med Hypotheses. 2019 Mar;124:7-12. doi: 10.1016/j.mehy.2019.01.008. Epub 2019 Jan 16. No abstract available.
citation: Hunter JP, Katz J, Davis KD. The effect of tactile and visual sensory inputs on phantom limb awareness. Brain. 2003 Mar;126(Pt 3):579-89. doi: 10.1093/brain/awg054.
citation: Hunter JP, Katz J, Davis KD. Stability of phantom limb phenomena after upper limb amputation: a longitudinal study. Neuroscience. 2008 Oct 28;156(4):939-49. doi: 10.1016/j.neuroscience.2008.07.053. Epub 2008 Aug 3.
citation: Imam B, Miller WC, Finlayson HC, Eng JJ, Jarus T. Incidence of lower limb amputation in Canada. Can J Public Health. 2017 Nov 9;108(4):e374-e380. doi: 10.17269/cjph.108.6093.
citation: Kilteni K, Groten R, Slater M. The Sense of Embodiment in Virtual Reality. Presence: Teleoperators and Virtual Environments. 2012; 21(4): 373-387.
citation: Krutki P, Mrowczynski W, Baczyk M, Lochynski D, Celichowski J. Adaptations of motoneuron properties after weight-lifting training in rats. J Appl Physiol (1985). 2017 Sep 1;123(3):664-673. doi: 10.1152/japplphysiol.00121.2017. Epub 2017 Jun 8.
citation: Marshall HM, Jensen MP, Ehde DM, Campbell KM. Pain site and impairment in individuals with amputation pain. Arch Phys Med Rehabil. 2002 Aug;83(8):1116-9. doi: 10.1053/apmr.2002.33121.
citation: Matjacic Z, Burger H. Dynamic balance training during standing in people with trans-tibial amputation: a pilot study. Prosthet Orthot Int. 2003 Dec;27(3):214-20. doi: 10.1080/03093640308726684.
citation: Montoya P, Larbig W, Grulke N, Flor H, Taub E, Birbaumer N. The relationship of phantom limb pain to other phantom limb phenomena in upper extremity amputees. Pain. 1997 Aug;72(1-2):87-93. doi: 10.1016/s0304-3959(97)00004-3.
citation: Moseley GL, Brugger P. Interdependence of movement and anatomy persists when amputees learn a physiologically impossible movement of their phantom limb. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18798-802. doi: 10.1073/pnas.0907151106. Epub 2009 Oct 26.
citation: Ortiz-Catalan M, Guethmundsdottir RA, Kristoffersen MB, Zepeda-Echavarria A, Caine-Winterberger K, Kulbacka-Ortiz K, Widehammar C, Eriksson K, Stockselius A, Ragno C, Pihlar Z, Burger H, Hermansson L. Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain: a single group, clinical trial in patients with chronic intractable phantom limb pain. Lancet. 2016 Dec 10;388(10062):2885-2894. doi: 10.1016/S0140-6736(16)31598-7. Epub 2016 Dec 2.
citation: Rudy TE, Lieber SJ, Boston JR, Gourley LM, Baysal E. Psychosocial predictors of physical performance in disabled individuals with chronic pain. Clin J Pain. 2003 Jan-Feb;19(1):18-30. doi: 10.1097/00002508-200301000-00003.
citation: Schafer ZA, Perry JL, Vanicek N. A personalised exercise programme for individuals with lower limb amputation reduces falls and improves gait biomechanics: A block randomised controlled trial. Gait Posture. 2018 Jun;63:282-289. doi: 10.1016/j.gaitpost.2018.04.030. Epub 2018 Apr 30.
citation: Schoenfeld BJ. The mechanisms of muscle hypertrophy and their application to resistance training. J Strength Cond Res. 2010 Oct;24(10):2857-72. doi: 10.1519/JSC.0b013e3181e840f3.
citation: Sin EI, Thong SY, Poon KH. Incidence of phantom limb phenomena after lower limb amputations in a Singapore tertiary hospital. Singapore Med J. 2013 Feb;54(2):75-81. doi: 10.11622/smedj.2013028.
citation: Srinivasan SS, Gutierrez-Arango S, Teng AC, Israel E, Song H, Bailey ZK, Carty MJ, Freed LE, Herr HM. Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation. Proc Natl Acad Sci U S A. 2021 Mar 2;118(9):e2019555118. doi: 10.1073/pnas.2019555118.
citation: Stankevicius A, Wallwork SB, Summers SJ, Hordacre B, Stanton TR. Prevalence and incidence of phantom limb pain, phantom limb sensations and telescoping in amputees: A systematic rapid review. Eur J Pain. 2021 Jan;25(1):23-38. doi: 10.1002/ejp.1657. Epub 2020 Sep 28.
citation: Trevelyan EG, Turner WA, Robinson N. Perceptions of phantom limb pain in lower limb amputees and its effect on quality of life: a qualitative study. Br J Pain. 2016 May;10(2):70-7. doi: 10.1177/2049463715590884. Epub 2015 Jun 23.
citation: Yaghi K, Yaghi Y, McDonald AA, Yadegarfar G, Cecil E, Seidl J, Dubois E, Rawaf S, Majeed A. Diabetes or war? Incidence of and indications for limb amputation in Lebanon, 2007. East Mediterr Health J. 2012 Dec;18(12):1178-86.