Study of Lower-limb Phantom Pain Syndrome Using Peripheral Nerve and Spinal Cord Stimulation

NCT05807607 | Unknown

• 1 other identifier: DVFU-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Brief Summary: 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 lower 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.

Conditions

Phantom Limb Pain; Phantom Pain; Amputation; Lower Limb Amputation

Keywords

Neurostimulation; Spinal cord stimulation; Peripheral nerve stimulation; Phantom limb pain; Pain suppression; Lower-limb amputation

Outcome Measures

Primary Outcomes (4)

• Determining the effectiveness of phantom pain suppression based on the Test Stimulation Diary

  The patient completes a Test Stimulation Diary at the end of each day, noting the location of phantom pain and the percentage of pain reduction during stimulation.

  up to 1 month

• Change according to the scale of the DN4 Neuropathic Pain Questionnaire

  The DN4 Neuropathic Pain Questionnaire defines the neuropathic nature of pain with a point of 4 to 10.

  : baseline and up to 1 month

• Change according to the scale of the PainDetect questionnaire

  The PainDetect questionnaire reflects all possible parameters of pain and allows us to very clearly track the picture of the pain syndrome in dynamics. The score is made in the range from 0 (best score) to 38 (worst score) points.

  up to 1 month

• Change in relative power in slow frequencies (alpha and theta ranges) on the EEG with the neurostimulator on/off and eyes open/closed.

  Data analysis is done in MNE Python. An average reference is used. Artifact correction is carried out using the analysis of independent components. Additionally, band-pass filtering is applied in the range from 1 to 40 Hz. The general analysis pipeline includes the calculation of the normalized power spectral density, after which the average power of the alpha rhythm is divided by the average power of the theta rhythm. This ratio is compared under different experimental conditions

  up to 1 month

Study Arms (1)

Patients who underwent the lower limb amputation and have phantom pain syndrome

EXPERIMENTAL

Procedure: Implantation of PNS electrodes during surgery, mapping to select sites with the best effect and daily modulation.; Procedure: SCS electrode implantation at surgery, mapping to select sites with the best effect and pain modulation; Procedure: Change according to the scale of the PainDetect questionnaire

Interventions

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

Patients who underwent the lower limb amputation and have phantom pain syndrome

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

SСS 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. 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.

Patients who underwent the lower limb amputation and have phantom pain syndrome

Change according to the scale of the PainDetect questionnaire 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) in order to return the patient to the 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.

Patients who underwent the lower limb amputation and have phantom pain syndrome

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with implanted neuromodulation devices.
• Amputation of the lower limb.
• Age ranges from 18 to 65 years old.
• The duration from the moment of amputation is from 12 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.

You may not qualify if:

• The presence of severe somatic pathology that prevents surgical treatment and participation in the study.
• The presence of mental illness (including history), severe depression, suicidal tendencies, history of suicide.
• The presence of gross orthopedic deformity in the limb above the amputation level.
• History of oncology.
• History of epilepsy.
• Complicated TBI or history of stroke.
• The impossibility of conducting electrical stimulation due to another somatic pathology.
• Purulent septic pathology.
• Drug addiction (including history).
• Congenital malformation of the lower limb.
• Anomalies in the development of the CNS.

Sponsors & Collaborators

• Artur Biktimirov: lead

Study Sites (1)

Far Eastern Federal University (FEFU)

Vladivostok, Primorskiy (Maritime) Kray, 690922, Russia

Location

Related Publications (12)

• 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.

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• 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.

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• 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.

  PMID: 31870766 BACKGROUND

• 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.

  PMID: 32348644 BACKGROUND

• 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.

  PMID: 25298320 BACKGROUND

• 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.

  PMID: 30517154 BACKGROUND

• 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.

  PMID: 30474259 BACKGROUND

• 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.

  PMID: 24500407 BACKGROUND

• Dietrich C, Nehrdich S, Seifert S, Blume KR, Miltner WHR, Hofmann GO, Weiss T. Leg Prosthesis With Somatosensory Feedback Reduces Phantom Limb Pain and Increases Functionality. Front Neurol. 2018 Apr 26;9:270. doi: 10.3389/fneur.2018.00270. eCollection 2018.

  PMID: 29755399 BACKGROUND

• 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.

  PMID: 18281705 BACKGROUND

• 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.

  PMID: 31501600 BACKGROUND

• Rathnayake A, Saboo A, Malabu UH, Falhammar H. Lower extremity amputations and long-term outcomes in diabetic foot ulcers: A systematic review. World J Diabetes. 2020 Sep 15;11(9):391-399. doi: 10.4239/wjd.v11.i9.391.

  PMID: 32994867 BACKGROUND

MeSH Terms

Conditions

Phantom Limb

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Far Eastern Federal University

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 11, 2023
• Study Start: November 17, 2022
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 11, 2023

Record last verified: 2023-03

Locations

RU (1)