The Role of Peripheral Afferents in Modulating Post-stroke Central Pain

Last updated: March 10, 2025
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Overall Status: Active - Recruiting

Phase

3

Condition

Stroke

Cerebral Ischemia

Treatment

Lidocaine 20mg/ml

Levobupivacaine Hydrochloride 1.25 MG/ML

Sodium Chloride 0.9% Inj

Clinical Study ID

NCT06446960
C23-05
2023-504676-17-00
  • Ages > 18
  • All Genders

Study Summary

Central post-stroke pain (CPP) is extremely difficult to relieve and responds very poorly to analgesics targeting neuropathic pain, probably because the mechanisms underlying this pain remain poorly understood.

Stroke pain is traditionally considered to be of central origin and related to changes in the spinal cord and/or brain nociceptive systems. However, a recent study in a small cohort of patients has suggested that the peripheral nervous system (PNS) may have a role in the initiation and persistence of APD.

The main objective of this prospective randomised controlled bicentric study (Raymond Poincaré and Ambroise Paré) in double blind and parallel groups against placebo (3 arms) will be to evaluate the efficacy of two peripheral nerve blocks performed 14 days apart on spontaneous neuropathic pain after stroke. The active treatments used for the blocks will be either lidocaine 20 mg/ml or levobupivacaine 1.25 mg/ml or placebo (saline)

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patients aged 18 years and over with no maximum age (blocks are generally very welltolerated in the very elderly)

  2. Pain in the upper or lower limb distal enough to be completely covered by aperipheral nerve block

  3. Chronic pain for at least 6 months

  4. Ischaemic or haemorrhagic stroke for at least 6 months documented clinically and byappropriate imaging (MRI)

  5. Post-stroke central neuropathic pain defined as pain occurring in the aftermath ofstroke meeting the criteria for probable or defined neuropathic pain according tothe NeuPSIG algorithm and with a DN4 screening questionnaire score of at least 4 outof 10.

  6. Spontaneous pain intensity greater than or equal to 4 out of 10 on an 11-pointnumerical scale (EN) at inclusion and randomisation (i.e. just before each block)

  7. Patients affiliated to a social security scheme or beneficiaries of such a scheme

  8. Stable oral analgesic pharmacological treatment for at least 2 weeks prior toinclusion

  9. Acceptance and signing of the informed consent

Exclusion

Exclusion Criteria:

  1. Inability or unwillingness to sign an informed consent

  2. Person subject to a legal protection measure (safeguard of justice, curatorship,guardianship)

  3. Patients with ongoing psychiatric pathology (major depression, psychosis) orcognitive disorders that prevent a good understanding of the protocol andquestionnaires

  4. Pain that is too widespread in one hemicycle or limb and cannot be adequatelycovered by blocks

  5. Ongoing drug or substance abuse

  6. Language (aphasia) or comprehension disorders, illiteracy

  7. Moderate to severe renal or hepatic impairment

  8. Contraindication to local anaesthetics for use in perineural blocks (infection oracute inflammation in the injection area, known allergy).

  9. Pregnancy or breastfeeding

  10. Known hypersensitivity to lidocaine, levobupivacaine, amide-linked localanaesthetics or to any of the excipients contained in the specialities used in thestudy.

  11. Patients with recurrent porphyria or severe hypotension contraindicating treatmentwith lidocaine and/or levobupivacaine

  12. Current treatment with antiarrhythmic drugs causing torsades de pointes (amiodarone,disopyramide, quinidinics, sotalol...) or with antiarrhythmic drugs with localanaesthetic activity (mexiletine or class III antiarrhythmic drugs) and cannot bediscontinued.

  13. Too little pain at the time of the blocks (< 4 out of 10)

  14. Need to modify analgesic pharmacological treatment at the beginning or during thestudy

Study Design

Total Participants: 36
Treatment Group(s): 3
Primary Treatment: Lidocaine 20mg/ml
Phase: 3
Study Start date:
February 12, 2024
Estimated Completion Date:
February 12, 2027

Study Description

The primary endpoint will be the change in neuropathic pain intensity (assessed on an 11-point pain intensity scale), expressed as a difference in pain intensity between the value obtained before each block and that obtained 45 minutes after, corresponding to the maximum expected effect. Secondary endpoints will include exertional pain, pain quality, % relief, clinical global impression, pain assessment on a patient diary for a fortnight after each block and adverse events.

Patients will be randomised to receive one of 3 study treatments (lidocaine 2%, levobupivacaine 1.25 mg/ml or placebo). The treatment protocol will involve 2 perineural blocks performed 14 days apart. Assessment will continue for up to 2 weeks after each block, i.e. up to one month after the start of treatment. An evaluation of pain will be carried out before the block and after each block, at 45 minutes and at 5 hours, and then daily by the patient on a self-evaluation booklet for the 14 days following each block.

Randomisation will be centralised on a server from a list drawn up in advance by computer rogramme, balanced by blocks of variable size. Allocation between the 3 arms will be done according to a balanced 1:1:1 distribution. Treatments will be numbered from 1 to n, and allocated to patients in the chronological order of their inclusion in the trial.

Patients will be randomised on the day of treatment using a centralised computerised randomisation procedure to receive one of the 3 study treatments (lidocaine 20 mg/ml levobupivacaine 1.25 mg/ml or saline). No matching by age or duration of pain is planned, as randomisation usually results in groups matched at baseline on these criteria. The treatment will be administered over two visits performed 14 days apart by a qualified anaesthetist using the peri-nervous route according to current ecommendations (see above). Only one randomisation will be performed at baseline, so that a patient on active treatment cannot receive placebo at a later date and vice versa (see figure 1).

The investigators plan to randomise 10 patients per group and a total of 30 patients to achieve 90% power with a two sided α risk=0.05,. Given the estimated premature discontinuation rate, the investigators consider it necessary to include 12 patients per group for a total of 36 patients.

This study opens the way to new therapeutic avenues for these patients who often fail all treatments

Connect with a study center

  • CHU Ambroise Paré

    Boulogne-Billancourt, 92100
    France

    Active - Recruiting

  • Hôpital Raymond Poincaré

    Garches, 92380
    France

    Active - Recruiting

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