Study of Phantom Limb Pain Using Peripheral Nerve and Spinal Cord Stimulation

NCT ID: NCT05650931

Last Updated: 2022-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-01

Study Completion Date

2025-11-01

Brief Summary

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The purpose of this study is to evaluate the effectiveness of neuromodulation for relief of phantom limb pain (PLP) using peripheral nerve (PNS) and spinal cord (SCS) stimulation with implantable electrodes. The researchers expect that PLP in patients with upper limb amputation will be relieved by peripheral nerve and the spinal cord stimulation. The possibility of finding EEG biomarkers for phantom pain will be explored.

Detailed Description

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The purpose of this study is to evaluate the effectiveness of neuromodulation for relief of phantom limb pain (PLP) using peripheral nerve (PNS) and spinal cord stimulation (SCS) with implantable electrodes.

The study is conducted to collect information on the role of non-adaptive neuroplasticity and inhibitory descending antinociceptive influences, which determine the effect of peripheral nerve and spinal cord stimulation with implanted electrodes in patients with phantom limb pain as a result of amputation of the upper limb. Neuromodulation is a potential treatment option for chronic pain that may alter maladaptive neuroplasticity and enhance descending inhibitory pathways.

Study participants will be selected according to the inclusion criteria. Next, multichannel electrodes will be implanted in the region of the target peripheral nerves of the amputated limb and the corresponding segments of the spinal cord. The evaluation of the therapeutic effects of pain syndromes will be carried out in the mode of long-term repetitive nerve stimulation. Postoperative follow-up will be carried out from 2 weeks to 1 month. During the follow-up period, patients will complete scales and questionnaires daily.

The stimulator is turned on the day after surgery to assess pain relief. The patient is explained the rules for using the stimulator. The selection of stimulation parameters is carried out according to the generally accepted methodology (the stimulation zone should overlap the pain zone; stimulation should be in the nature of pleasant vibrations). The patient will be given a test stimulation diary to complete every day (at the end of the day) during the entire stimulation period.

The researchers expect that phantom limb pain in patients undergoing upper limb amputation will be relieved by peripheral nerve stimulation. We will explore the possibility of creating a personal phantom sensitivity map to optimize the stimulation program. We will study improving the quality of life and reducing pain.

Patients will be asked to participate in an experiment using electroencephalography (EEG) starting on the 3rd day after implantation. The purpose of this entry is to investigate the bimarkers of phantom pain. As part of the experimental procedure, we plan to sequentially turn off the stimulator until the patient returns to the preoperative pain state, and also turn on the stimulator with fixation of the moments of pain suppression to the level at the beginning of the experiment. During the entire period, the patient's EEG will be recorded. The researchers expect to see changes in alpha and theta EEG rhythms under these experimental conditions.

Conditions

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Phantom Limb Pain Phantom Pain Amputation

Keywords

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neurostimulation spinal cord stimulation phantom limb pain pain suppression upper-limb amputation

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Patients who underwent the upper limb amputation and have phantom limb pain

Group Type EXPERIMENTAL

Implantation of PNS electrodes during surgery, mapping to select sites with the best effect and pain modulation.

Intervention Type PROCEDURE

PNS electrodes are implanted in the area of peripheral nerves of the amputated limb. During phantom pain mapping, multichannel electrodes are used to stimulate peripheral nerves at different sites in the stump. Stimulation turns on sequentially at different stimulation sites; sites are selected where pain is most effectively suppressed. These sites are assigned to the patient for daily modulation.

SCS electrode implantation at surgery, mapping to select sites with the best effect and pain modulation.

Intervention Type PROCEDURE

SNS electrodes are implanted in the area of targeted peripheral nerves in the amputated limb. During phantom pain mapping, multichannel electrodes are used to stimulate the spinal cord at different sites in the cervical thickening (C5-T1). Stimulation starts at a specific site at a frequency of 1 Hz and increases by 0.1 Hz until the patient no longer feels phantom pain. Stimulation turns on sequentially at different stimulation sites; sites are selected where pain is most effectively suppressed. These sites are assigned to the patient for daily modulation.

EEG to search for phantom pain biomarkers

Intervention Type PROCEDURE

This procedure uses the method of electroencephalography (EEG). EEG signals are recorded during the entire experiment. First, the patient is recorded at rest with stimulator on (PNS/SCS) with eyes open and then closed, in the stimulator off state (eyes open, then closed) when patient's pain returns to its preoperative state. The stimulation is then turned back on to the original level of pain suppression. The moments of pain suppression are fixed by marking.

Interventions

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Implantation of PNS electrodes during surgery, mapping to select sites with the best effect and pain modulation.

PNS electrodes are implanted in the area of peripheral nerves of the amputated limb. During phantom pain mapping, multichannel electrodes are used to stimulate peripheral nerves at different sites in the stump. Stimulation turns on sequentially at different stimulation sites; sites are selected where pain is most effectively suppressed. These sites are assigned to the patient for daily modulation.

Intervention Type PROCEDURE

SCS electrode implantation at surgery, mapping to select sites with the best effect and pain modulation.

SNS electrodes are implanted in the area of targeted peripheral nerves in the amputated limb. During phantom pain mapping, multichannel electrodes are used to stimulate the spinal cord at different sites in the cervical thickening (C5-T1). Stimulation starts at a specific site at a frequency of 1 Hz and increases by 0.1 Hz until the patient no longer feels phantom pain. Stimulation turns on sequentially at different stimulation sites; sites are selected where pain is most effectively suppressed. These sites are assigned to the patient for daily modulation.

Intervention Type PROCEDURE

EEG to search for phantom pain biomarkers

This procedure uses the method of electroencephalography (EEG). EEG signals are recorded during the entire experiment. First, the patient is recorded at rest with stimulator on (PNS/SCS) with eyes open and then closed, in the stimulator off state (eyes open, then closed) when patient's pain returns to its preoperative state. The stimulation is then turned back on to the original level of pain suppression. The moments of pain suppression are fixed by marking.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients with implanted neuromodulation devices.
* Amputation of the upper limb at the level of the forearm.
* Age ranges from 18 to 65 years old.
* The duration from the moment of amputation is from 6 months.
* The presence of persistent chronic pain syndrome is from 4 to 10 points according to the Visual Analogue Scale
* Absence of pregnancy at the time of implantation, confirmed by a pregnancy test.

Exclusion Criteria

* The presence of severe somatic pathology
* The presence of mental illness
* The presence of a gross orthopedic deformity in the limb above the amputation level.
* The presence of oncology.
* The presence of epilepsy.
* Complications after a traumatic brain injury or stroke.
* Purulent - septic pathology.
* Drug addiction.
* Congenital malformation of the upper limb.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Artur Biktimirov

OTHER

Sponsor Role lead

Responsible Party

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Artur Biktimirov

Far Eastern Federal University

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Far Eastern Federal University (FEFU)

Vladivostok, Primorskiy (Maritime) Kray, Russia

Site Status

Countries

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Russia

References

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Knotkova H, Hamani C, Sivanesan E, Le Beuffe MFE, Moon JY, Cohen SP, Huntoon MA. Neuromodulation for chronic pain. Lancet. 2021 May 29;397(10289):2111-2124. doi: 10.1016/S0140-6736(21)00794-7.

Reference Type BACKGROUND
PMID: 34062145 (View on PubMed)

Schiefer M, Tan D, Sidek SM, Tyler DJ. Sensory feedback by peripheral nerve stimulation improves task performance in individuals with upper limb loss using a myoelectric prosthesis. J Neural Eng. 2016 Feb;13(1):016001. doi: 10.1088/1741-2560/13/1/016001. Epub 2015 Dec 8.

Reference Type BACKGROUND
PMID: 26643802 (View on PubMed)

Graczyk EL, Schiefer MA, Saal HP, Delhaye BP, Bensmaia SJ, Tyler DJ. The neural basis of perceived intensity in natural and artificial touch. Sci Transl Med. 2016 Oct 26;8(362):362ra142. doi: 10.1126/scitranslmed.aaf5187.

Reference Type BACKGROUND
PMID: 27797958 (View on PubMed)

Mekhail N, Levy RM, Deer TR, Kapural L, Li S, Amirdelfan K, Hunter CW, Rosen SM, Costandi SJ, Falowski SM, Burgher AH, Pope JE, Gilmore CA, Qureshi FA, Staats PS, Scowcroft J, Carlson J, Kim CK, Yang MI, Stauss T, Poree L; Evoke Study Group. Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial. Lancet Neurol. 2020 Feb;19(2):123-134. doi: 10.1016/S1474-4422(19)30414-4. Epub 2019 Dec 20.

Reference Type BACKGROUND
PMID: 31870766 (View on PubMed)

Ortiz-Catalan M, Mastinu E, Sassu P, Aszmann O, Branemark R. Self-Contained Neuromusculoskeletal Arm Prostheses. N Engl J Med. 2020 Apr 30;382(18):1732-1738. doi: 10.1056/NEJMoa1917537.

Reference Type BACKGROUND
PMID: 32348644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25298320 (View on PubMed)

Schiefer MA, Graczyk EL, Sidik SM, Tan DW, Tyler DJ. Artificial tactile and proprioceptive feedback improves performance and confidence on object identification tasks. PLoS One. 2018 Dec 5;13(12):e0207659. doi: 10.1371/journal.pone.0207659. eCollection 2018.

Reference Type BACKGROUND
PMID: 30517154 (View on PubMed)

Petrini FM, Valle G, Strauss I, Granata G, Di Iorio R, D'Anna E, Cvancara P, Mueller M, Carpaneto J, Clemente F, Controzzi M, Bisoni L, Carboni C, Barbaro M, Iodice F, Andreu D, Hiairrassary A, Divoux JL, Cipriani C, Guiraud D, Raffo L, Fernandez E, Stieglitz T, Raspopovic S, Rossini PM, Micera S. Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback. Ann Neurol. 2019 Jan;85(1):137-154. doi: 10.1002/ana.25384. Epub 2018 Dec 24.

Reference Type BACKGROUND
PMID: 30474259 (View on PubMed)

Raspopovic S, Capogrosso M, Petrini FM, Bonizzato M, Rigosa J, Di Pino G, Carpaneto J, Controzzi M, Boretius T, Fernandez E, Granata G, Oddo CM, Citi L, Ciancio AL, Cipriani C, Carrozza MC, Jensen W, Guglielmelli E, Stieglitz T, Rossini PM, Micera S. Restoring natural sensory feedback in real-time bidirectional hand prostheses. Sci Transl Med. 2014 Feb 5;6(222):222ra19. doi: 10.1126/scitranslmed.3006820.

Reference Type BACKGROUND
PMID: 24500407 (View on PubMed)

Soghoyan G, Biktimirov AR, Piliugin NS, Matvienko Y, Kaplan AY, Sintsov MY, Lebedev MA. Restoration of natural somatic sensations to the amputees: finding the right combination of neurostimulation methods. Front Neurosci. 2024 Nov 25;18:1466684. doi: 10.3389/fnins.2024.1466684. eCollection 2024.

Reference Type DERIVED
PMID: 39654645 (View on PubMed)

Soghoyan G, Biktimirov A, Matvienko Y, Chekh I, Sintsov M, Lebedev MA. Peripheral nerve stimulation enables somatosensory feedback while suppressing phantom limb pain in transradial amputees. Brain Stimul. 2023 May-Jun;16(3):756-758. doi: 10.1016/j.brs.2023.04.017. Epub 2023 Apr 24.

Reference Type DERIVED
PMID: 37100202 (View on PubMed)

Other Identifiers

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DVFU-09

Identifier Type: -

Identifier Source: org_study_id