Enhancing Abilities in Amputees and Patients With Peripheral Neuropathy Through Restoration of Sensory Feedback

Diabetic Peripheral Neuropathy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04217005
• Other study ID #: 2019-N-97
• Status: Recruiting
• Phase: N/A
• Start date: December 13, 2019
• Est. completion date: January 15, 2026

Study information

• Verified date: February 2024
• Source: ETH Zurich
• Contact: greta preatoni, PhD
• Phone: 766274077
• Email: gretapreatoni1[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 15, 2026
• Est. primary completion date: December 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Peripheral Neuropathy
• Lower Limb Amputation Above Knee (Injury)
• Lower Limb Amputation Below Knee (Injury)
• Lower Limb Amputation Knee
• Peripheral Nervous System Diseases
• Wounds and Injuries

Intervention

Device:
• Sensory Feedback
Subjects will receive a sensory feedback provided by electrical stimulation

Locations

Country	Name	City	State
Switzerland	ETH Zurich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
ETH Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (22)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Visual Analogue scale for pain throughout the study	Subjects will complete VAS scale to measure pain level (from 0 to 10, 10 is worst pain immaginable)	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
Primary	Change between tasks with sensory feedback and with no sensory feedback in Ground Reaction Forces	GRF will be assessed during motor perfomances of the subjects	during motor tasks up to 3 weeks
Primary	Change between tasks with sensory feedback and with no sensory feedback in Centre of Mass and Pressure	CoM and CoP will be assessed during motor perfomances of the subjects	during motor tasks up to 3 weeks
Primary	Change from baseline and between tasks with sensory feedback and with no sensory feedback in Vo2 consumption	metabolic consumption is going to be measured with mobile spiroergometry and compared after walking with and without sensory feedback	during motor tasks up to 3 weeks
Primary	Change from baseline between tasks with sensory feedback and with no sensory feedback in Embodiment	Embodiment will be measured with questionnaires (from -3 to +3, +3 totally agrees; two questions are from 1 to 10 (to measure vividness, where 10 is max vividness) and from 1 to 100 (to measure prevalence, where 100 is max duration of the embodiment feeling))	immediately after sessions up to 3 weeks
Primary	Change between tasks with sensory feedback and with no sensory feedback in Visual Analogue scale for confidence	Subjects will complete VAS scale to measure confidence level (from 0 to 10, where 10 is max confidence)	immediately after sessions up to three weeks
Primary	Change between tasks with sensory feedback and with no sensory feedback in Joint torque	kinematic measurement	during motor tasks up to three weeks
Primary	Change in Proprioceptive drift between different conditions	To measure embodiment subjects will be asked after VR sessions to indicate where they feel their leg without looking at the limb in real world. This is a measure of embodiment.	Immediately after sessions in Virtual Reality up to three weeks
Primary	Change in Telescoping measures between different conditions	To measure embodiment subjects will be asked after VR sessions to indicate how long they feel their leg without looking at the limb in real world. This is a measure of embodiment.	Immediately after sessions in Virtual Reality up to three weeks
Secondary	Trinity Amputation and Prosthesis Experiences Scales	Subjects will fill the TAPES to measure their satisfaction with the prosthesis (Scores range from 5 to 25, with higher scores indicating greater levels of adjustment)	Immediately before intervention
Secondary	Change in Quality of Life in Neurological Disorders	QoL will be assessed through questionnaires to see if the intevention had impact on this aspect (All Neuro-QOL banks and scales are scored such that a high score reflects more of what is being measured)	one week before first session and one week after last session
Secondary	Amputee Mobility Predictor	Subjects will perform AMPRO to assess K level (scores range from 0 to 47, correspoding to levels of mobility from 1(K1) to 4(K4), where 4 is the best level of mobility)	Immediately before the intervention