Clinical trial NCT04217005: Enhancing Abilities in Amputees and Patients With Peripheral Neuropathy Through Restoration of Sensory Feedback
Official title: Enhancing Functional and Cognitive Performances in People With Amputation and Peripheral Neuropathy Through the Restoration of Sensory Feedback in Real World and Virtual Reality Environments
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lower Limb Amputation Knee
Lower Limb Amputation Above Knee (Injury)
Lower Limb Amputation Below Knee (Injury)
Diabetic Peripheral Neuropathy
Lead sponsor: ETH Zurich
Sponsor class: OTHER
First posted: 2020-01-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Many amputees suffer from Phantom Limb Pain (PLP), a condition where painful perceptions arise from the missing limb. Leg amputees wear prostheses that do not provide any sensory feedback, apart from the stump-socket interaction. Increased physical effort associated with prosthesis use as well as discomfort often lead to rejection of artificial limbs. Additionally, the perception of the missing limb and its brain representation, do not match-up with what amputees see (the prosthesis) and this is made worse by the absence of sensory feedback. Therefore, re-establishing the sensory flow of information between the subject's brain and the prosthetic device is extremely important to avoid this mismatch, which creates inadequate embodiment. This study focuses on improving functional abilities and decreasing PLP in amputees thanks to the use of a system able to generate a sensory feedback (SF), which will be provided with a non-invasive electrical stimulation (ES). First, the possibility of enhancing the performance in different functional tasks thanks to the use of SF will be explored. Furthermore, it will be evaluated if SF enhances the prosthesis embodiment and helps restoring a multisensory integration (visuo-tactile), potentially providing also a pain relief. Once tested this system on amputees, also people with peripheral neuropathy and sensory loss will be recruited. Diabetic patients can suffer from symmetrical polyneuropathy (DSPN), which is a common complication caused by prolonged glucose unbalanced levels that lead to nerve damage. Non-invasive ES has been proposed and used as a therapy to treat the chronic pain conditions. In particular, TENS (transcutaneous electrical nerve stimulation) is a type of non-invasive ES, which is able to activate large diameter afferent fibers. The gate control theory of pain states that these large diameter fibers inhibit central nociceptive transmission with a resultant decrease in pain perception. Therefore, also these patients will be recruited to see whether adding a non-invasive SF can enhance their functional motor abilities while diminishing their pain.

The subjects will perform a pool of the following tasks, depending on their residual abilities: motor tasks (walking on ground level and on stairs), cognitive tasks (dual tasks), subjective evaluation of prosthesis weight and description of sensations from ES.

Some tasks will be performed in Virtual Reality environments with and without an active stimulation.


Eligibility criteria: Inclusion Criteria:

* transfemoral amputation or transtibial amputation or knee disarticulation or diabetic peripheral neuropathy
* the subject should be healthy other than the amputation and the diabetic neuropathy and in the range of 18-70 years old
* the subject should be able to comfortably walk, sit and stand alone

Exclusion Criteria:

* cognitive impairment
* pregnancy
* Prior or current psychological diseases such as borderline, schizophrenia, Depression or Maniac Depression
* acquired brain injury with residual impairment
* excessive sensitivity or pain to electrical stimulation with surface electrodes
* cybersickness

Primary outcomes:
measure: Change from baseline in Visual Analogue scale for pain throughout the study
timeFrame: one month before the study, 2 weeks before the study, immediately before the intervention, immediately after the intervento, after tasks with and without sensory feedback, 2 weeks after last intervention, 1 month after last intervention
measure: Change between tasks with sensory feedback and with no sensory feedback in Ground Reaction Forces
timeFrame: during motor tasks up to 3 weeks
measure: Change between tasks with sensory feedback and with no sensory feedback in Centre of Mass and Pressure
timeFrame: during motor tasks up to 3 weeks
measure: Change from baseline and between tasks with sensory feedback and with no sensory feedback in Vo2 consumption
timeFrame: during motor tasks up to 3 weeks
measure: Change from baseline between tasks with sensory feedback and with no sensory feedback in Embodiment
timeFrame: immediately after sessions up to 3 weeks
measure: Change between tasks with sensory feedback and with no sensory feedback in Visual Analogue scale for confidence
timeFrame: immediately after sessions up to three weeks
measure: Change between tasks with sensory feedback and with no sensory feedback in Joint torque
timeFrame: during motor tasks up to three weeks
measure: Change in Proprioceptive drift between different conditions
timeFrame: Immediately after sessions in Virtual Reality up to three weeks
measure: Change in Telescoping measures between different conditions
timeFrame: Immediately after sessions in Virtual Reality up to three weeks
Secondary outcomes:
measure: Trinity Amputation and Prosthesis Experiences Scales
timeFrame: Immediately before intervention
measure: Change in Quality of Life in Neurological Disorders
timeFrame: one week before first session and one week after last session
measure: Amputee Mobility Predictor
timeFrame: Immediately before the intervention
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: ETH Zurich
Study officials:
References:
citation: Abbott CA, Malik RA, van Ross ER, Kulkarni J, Boulton AJ. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care. 2011 Oct;34(10):2220-4. doi: 10.2337/dc11-1108. Epub 2011 Aug 18.
citation: Archer AG, Watkins PJ, Thomas PK, Sharma AK, Payan J. The natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychiatry. 1983 Jun;46(6):491-9. doi: 10.1136/jnnp.46.6.491.
citation: Burke MJ, Roman V, Wright V. Bone and joint changes in lower limb amputees. Ann Rheum Dis. 1978 Jun;37(3):252-4. doi: 10.1136/ard.37.3.252.
citation: Antfolk C, D'Alonzo M, Rosen B, Lundborg G, Sebelius F, Cipriani C. Sensory feedback in upper limb prosthetics. Expert Rev Med Devices. 2013 Jan;10(1):45-54. doi: 10.1586/erd.12.68.
citation: Oddo CM, Raspopovic S, Artoni F, Mazzoni A, Spigler G, Petrini F, Giambattistelli F, Vecchio F, Miraglia F, Zollo L, Di Pino G, Camboni D, Carrozza MC, Guglielmelli E, Rossini PM, Faraguna U, Micera S. Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans. Elife. 2016 Mar 8;5:e09148. doi: 10.7554/eLife.09148.
citation: Charkhkar H, Shell CE, Marasco PD, Pinault GJ, Tyler DJ, Triolo RJ. High-density peripheral nerve cuffs restore natural sensation to individuals with lower-limb amputations. J Neural Eng. 2018 Oct;15(5):056002. doi: 10.1088/1741-2552/aac964. Epub 2018 Jun 1.
citation: Chow DH, Cheng CT. Quantitative analysis of the effects of audio biofeedback on weight-bearing characteristics of persons with transtibial amputation during early prosthetic ambulation. J Rehabil Res Dev. 2000 May-Jun;37(3):255-60.
citation: Tan DW, Schiefer MA, Keith MW, Anderson JR, Tyler J, Tyler DJ. A neural interface provides long-term stable natural touch perception. Sci Transl Med. 2014 Oct 8;6(257):257ra138. doi: 10.1126/scitranslmed.3008669.
citation: Dailey DL, Rakel BA, Vance CGT, Liebano RE, Amrit AS, Bush HM, Lee KS, Lee JE, Sluka KA. Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia. Pain. 2013 Nov;154(11):2554-2562. doi: 10.1016/j.pain.2013.07.043. Epub 2013 Jul 27.
citation: Dosen S, Markovic M, Strbac M, Belic M, Kojic V, Bijelic G, Keller T, Farina D. Multichannel Electrotactile Feedback With Spatial and Mixed Coding for Closed-Loop Control of Grasping Force in Hand Prostheses. IEEE Trans Neural Syst Rehabil Eng. 2017 Mar;25(3):183-195. doi: 10.1109/TNSRE.2016.2550864. Epub 2016 Apr 7.
citation: Clippinger FW, Seaber AV, McElhaney JH, Harrelson JM, Maxwell GM. Afferent sensory feedback for lower extremity prosthesis. Clin Orthop Relat Res. 1982 Sep;(169):202-6.
citation: Rognini G, Petrini FM, Raspopovic S, Valle G, Granata G, Strauss I, Solca M, Bello-Ruiz J, Herbelin B, Mange R, D'Anna E, Di Iorio R, Di Pino G, Andreu D, Guiraud D, Stieglitz T, Rossini PM, Serino A, Micera S, Blanke O. Multisensory bionic limb to achieve prosthesis embodiment and reduce distorted phantom limb perceptions. J Neurol Neurosurg Psychiatry. 2019 Jul;90(7):833-836. doi: 10.1136/jnnp-2018-318570. Epub 2018 Aug 12. No abstract available.
citation: Sadeghi H, Allard P, Prince F, Labelle H. Symmetry and limb dominance in able-bodied gait: a review. Gait Posture. 2000 Sep;12(1):34-45. doi: 10.1016/s0966-6362(00)00070-9.
citation: Naschitz JE, Lenger R. Why traumatic leg amputees are at increased risk for cardiovascular diseases. QJM. 2008 Apr;101(4):251-9. doi: 10.1093/qjmed/hcm131. Epub 2008 Feb 16.
citation: Kumar D, Marshall HJ. Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation. Diabetes Care. 1997 Nov;20(11):1702-5. doi: 10.2337/diacare.20.11.1702.
citation: Kumar D, Alvaro MS, Julka IS, Marshall HJ. Diabetic peripheral neuropathy. Effectiveness of electrotherapy and amitriptyline for symptomatic relief. Diabetes Care. 1998 Aug;21(8):1322-5. doi: 10.2337/diacare.21.8.1322.
citation: Lotze M, Moseley GL. Role of distorted body image in pain. Curr Rheumatol Rep. 2007 Dec;9(6):488-96. doi: 10.1007/s11926-007-0079-x.
citation: Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965 Nov 19;150(3699):971-9. doi: 10.1126/science.150.3699.971. No abstract available.
citation: Petrini FM, Bumbasirevic M, Valle G, Ilic V, Mijovic P, Cvancara P, Barberi F, Katic N, Bortolotti D, Andreu D, Lechler K, Lesic A, Mazic S, Mijovic B, Guiraud D, Stieglitz T, Alexandersson A, Micera S, Raspopovic S. Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain. Nat Med. 2019 Sep;25(9):1356-1363. doi: 10.1038/s41591-019-0567-3. Epub 2019 Sep 9.
citation: Petrini FM, Valle G, Bumbasirevic M, Barberi F, Bortolotti D, Cvancara P, Hiairrassary A, Mijovic P, Sverrisson AO, Pedrocchi A, Divoux JL, Popovic I, Lechler K, Mijovic B, Guiraud D, Stieglitz T, Alexandersson A, Micera S, Lesic A, Raspopovic S. Enhancing functional abilities and cognitive integration of the lower limb prosthesis. Sci Transl Med. 2019 Oct 2;11(512):eaav8939. doi: 10.1126/scitranslmed.aav8939.
citation: Crea S, Edin BB, Knaepen K, Meeusen R, Vitiello N. Time-Discrete Vibrotactile Feedback Contributes to Improved Gait Symmetry in Patients With Lower Limb Amputations: Case Series. Phys Ther. 2017 Feb 1;97(2):198-207. doi: 10.2522/ptj.20150441. No abstract available.
citation: Bruce D, Hunter M, Peters K, Davis T, Davis W. Fear of falling is common in patients with type 2 diabetes and is associated with increased risk of falls. Age Ageing. 2015 Jul;44(4):687-90. doi: 10.1093/ageing/afv024. Epub 2015 Mar 3.