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Impact of Peripheral Afferent Input on Central Neuropathic Pain

Primary Purpose

Spinal Cord Injuries, Spinal Cord Diseases, Syringomyelia

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Lidocaine (10 mg/ml)
Isotonic saline
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Spinal Cord Injuries focused on measuring central pain, peripheral afferent input, neuropathic pain, spinal cord injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Definite central neuropathic pain according to current diagnostic algorithms involving at least both feet or both hands bilaterally and symmetrically with regard to the expected neuroanatomical distribution of the nerve block. Patients with spinal cord injury. For patients with pain in both legs, the injury has to be incomplete. For patients with pain in both arms, the injury can be complete or incomplete. The pain in the area that will be investigated (region of interest) has to be in an area with at least some preservation of sensation An intensity of spontaneous pain of ≥4 NRS [0-10] in the region of interest during the screening visit and at the day of the intervention. Participant is able and willing to give informed consent. For female subjects of childbearing potential: A negative pregnancy test and either use of highly effective contraception or sexual abstinence Exclusion Criteria: Conus/cauda involvement or evidence of peripheral neuropathic pain due to documented peripheral lesion. Other known neurological and psychiatric conditions History or symptoms of significant diseases that may confound the measurements or represent contra-indications for the intervention (e.g., neuropathy following cancer or metabolic diseases such as diabetes mellitus, liver diseases, and kidney diseases. Cardiovascular diseases that preclude the anaesthetic intervention (e.g., arrythmias). Concomitant nociceptive pain within the innervation territory of the planned nerve block. Unable to understand and speak Danish Changes in pain medication within the last 4 weeks prior to the intervention. Treatment with warfarin or other blood thinning medications, that contraindicates regional anesthesia if the treating physician cannot recommend that such treatments are paused for at least 7 days before the study day Infection or skin disease in planned injection area Allergy for local anesthetics Pregnancy or lactation. Alcohol or drug abuse Pain intensity below 4 in the region of interest at the baseline measurement before the nerve block

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Lidocaine

    Isotonic saline

    Arm Description

    Nerve block

    Nerve block

    Outcomes

    Primary Outcome Measures

    Indication of most pain relief
    Limb with most pain relief on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] 40 minutes after nerve block

    Secondary Outcome Measures

    Intensity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] of spontaneous pain
    Intensity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] of spontaneous pain in the pre-specified region covered by the block 40, 60 and 90 min after the nerve block compared to baseline
    Pain relief 45 min after the nerve block
    Pain relief 45 min after the nerve block using a 6-point verbal scale ranging from worse pain to no, little, moderate, good and complete pain relief (-1 to 4)
    Pain extent [% of body surface on standardized pain drawings] 50 minutes after the nerve block
    Pain extent will be mapped on standardized pain drawings 50 minutes after the nerve block compared to baseline
    Pain descriptors 50 minutes after the nerve block
    Pain descriptors (burning, squeezing, pins and needles, tingling, stabbing, electrical shocks) are captured 50 minutes after the nerve block compared to baseline
    Area [% of pain extent] of hypersensitivity to thermal and nociceptive stimuli
    Area of hypersensitivity [% of pain extent] to warm (40°C) and cold (20°C) thermo rollers (Somedic AB, Hörby, Sweden), pinprick (Semmes-Weinstein monofilament no 5.88 (bending force 75.9 g/745 mN)), and brush (SENSELab Brush-05; Somedic AB, Hörby, Sweden), if any, 55 and 95 min after nerve block compared to baseline
    Intensity of hypersensitivity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] to thermal and nociceptive stimuli
    Intensity of hypersensitivity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] to warm (40°C) and cold (20°C) thermo rollers (Somedic AB, Hörby, Sweden), pinprick (Semmes-Weinstein monofilament no 5.88 (bending force 75.9 g/745 mN)), and brush (SENSELab Brush-05; Somedic AB, Hörby, Sweden), if any, 55 and 95 min after nerve block compared to baseline

    Full Information

    First Posted
    November 14, 2022
    Last Updated
    December 2, 2022
    Sponsor
    University of Aarhus
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05646810
    Brief Title
    Impact of Peripheral Afferent Input on Central Neuropathic Pain
    Official Title
    Impact of Peripheral Afferent Input on Central Neuropathic Pain
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2022 (Anticipated)
    Primary Completion Date
    September 30, 2023 (Anticipated)
    Study Completion Date
    December 31, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Aarhus

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The overarching aim of this study is to investigate the contribution of peripheral afferent input to spontaneous and evoked central neuropathic pain after a spinal cord lesion or disease.
    Detailed Description
    A key question that has been subject to longstanding debates in the field relates to the sites and mechanisms within the peripheral or central nervous system that potentially perpetuate chronic spontaneous and evoked central neuropathic pain. The investigators hypothesize that spontaneous central neuropathic pain depends on continuous, "physiological" somatosensory input from the painful body region in the periphery. Thus, spontaneous central neuropathic pain results from pathological gain control in central somatosensory networks with decreased activation thresholds for thermo- and mechanosensitive peripheral afferents.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Spinal Cord Injuries, Spinal Cord Diseases, Syringomyelia
    Keywords
    central pain, peripheral afferent input, neuropathic pain, spinal cord injury

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Lidocaine
    Arm Type
    Active Comparator
    Arm Description
    Nerve block
    Arm Title
    Isotonic saline
    Arm Type
    Placebo Comparator
    Arm Description
    Nerve block
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    Lidocaine (10 mg/ml)
    Intervention Description
    Lidocaine (10 mg/ml) will be injected according to established protocols using ultrasound guidance and an aseptic technique by an experienced anesthesiologist.
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    Isotonic saline
    Intervention Description
    Isotonic saline will be injected according to established protocols using ultrasound guidance and an aseptic technique by an experienced anesthesiologist.
    Primary Outcome Measure Information:
    Title
    Indication of most pain relief
    Description
    Limb with most pain relief on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] 40 minutes after nerve block
    Time Frame
    40 minutes
    Secondary Outcome Measure Information:
    Title
    Intensity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] of spontaneous pain
    Description
    Intensity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] of spontaneous pain in the pre-specified region covered by the block 40, 60 and 90 min after the nerve block compared to baseline
    Time Frame
    90 minutes
    Title
    Pain relief 45 min after the nerve block
    Description
    Pain relief 45 min after the nerve block using a 6-point verbal scale ranging from worse pain to no, little, moderate, good and complete pain relief (-1 to 4)
    Time Frame
    45 minutes
    Title
    Pain extent [% of body surface on standardized pain drawings] 50 minutes after the nerve block
    Description
    Pain extent will be mapped on standardized pain drawings 50 minutes after the nerve block compared to baseline
    Time Frame
    50 minutes
    Title
    Pain descriptors 50 minutes after the nerve block
    Description
    Pain descriptors (burning, squeezing, pins and needles, tingling, stabbing, electrical shocks) are captured 50 minutes after the nerve block compared to baseline
    Time Frame
    50 minutes
    Title
    Area [% of pain extent] of hypersensitivity to thermal and nociceptive stimuli
    Description
    Area of hypersensitivity [% of pain extent] to warm (40°C) and cold (20°C) thermo rollers (Somedic AB, Hörby, Sweden), pinprick (Semmes-Weinstein monofilament no 5.88 (bending force 75.9 g/745 mN)), and brush (SENSELab Brush-05; Somedic AB, Hörby, Sweden), if any, 55 and 95 min after nerve block compared to baseline
    Time Frame
    95 minutes
    Title
    Intensity of hypersensitivity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] to thermal and nociceptive stimuli
    Description
    Intensity of hypersensitivity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] to warm (40°C) and cold (20°C) thermo rollers (Somedic AB, Hörby, Sweden), pinprick (Semmes-Weinstein monofilament no 5.88 (bending force 75.9 g/745 mN)), and brush (SENSELab Brush-05; Somedic AB, Hörby, Sweden), if any, 55 and 95 min after nerve block compared to baseline
    Time Frame
    95 minutes
    Other Pre-specified Outcome Measures:
    Title
    Plasma lidocaine concentrations
    Description
    Plasma lidocaine concentrations approx. 40 min after the block.
    Time Frame
    40 minutes

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Definite central neuropathic pain according to current diagnostic algorithms involving at least both feet or both hands bilaterally and symmetrically with regard to the expected neuroanatomical distribution of the nerve block. Patients with spinal cord injury. For patients with pain in both legs, the injury has to be incomplete. For patients with pain in both arms, the injury can be complete or incomplete. The pain in the area that will be investigated (region of interest) has to be in an area with at least some preservation of sensation An intensity of spontaneous pain of ≥4 NRS [0-10] in the region of interest during the screening visit and at the day of the intervention. Participant is able and willing to give informed consent. For female subjects of childbearing potential: A negative pregnancy test and either use of highly effective contraception or sexual abstinence Exclusion Criteria: Conus/cauda involvement or evidence of peripheral neuropathic pain due to documented peripheral lesion. Other known neurological and psychiatric conditions History or symptoms of significant diseases that may confound the measurements or represent contra-indications for the intervention (e.g., neuropathy following cancer or metabolic diseases such as diabetes mellitus, liver diseases, and kidney diseases. Cardiovascular diseases that preclude the anaesthetic intervention (e.g., arrythmias). Concomitant nociceptive pain within the innervation territory of the planned nerve block. Unable to understand and speak Danish Changes in pain medication within the last 4 weeks prior to the intervention. Treatment with warfarin or other blood thinning medications, that contraindicates regional anesthesia if the treating physician cannot recommend that such treatments are paused for at least 7 days before the study day Infection or skin disease in planned injection area Allergy for local anesthetics Pregnancy or lactation. Alcohol or drug abuse Pain intensity below 4 in the region of interest at the baseline measurement before the nerve block
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Nanna B. Finnerup, Professor
    Phone
    0045 784 63380
    Email
    finnerup@clin.au.dk
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jan Rosner, MD
    Phone
    0041 79 952 4551
    Email
    jan.rosner@balgrist.ch
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jan Rosner, MD
    Organizational Affiliation
    Danish Pain Research Center, Department of Clinical Medicine, Aarhus University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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