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

NCT06446960 | Recruiting Phase 3

• 2 other identifiers: C23-052023-504676-17-00
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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)

Conditions

Stroke

Keywords

Ischemic Stroke; Central Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• 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 20mg/ml or levobupivacaine 1.25mg/ml or placebo (saline)

  The evolution in neuropathic pain intensity assessed on an 11-point pain intensity scale (0 = no pain: 10: maximum imaginable pain), 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. The values obtained before and after each block will first be analysed individually and then combined for the two successive blocks for each patient and the comparison will be between the three treatment arms, lidocaine 20mg/ml, levobupivacaine 1.25mg/ml or placebo Rationale for the choice of the main criterion : Pain intensity will be assessed on a numerical scale that corresponds to the usual validated measurement criterion and the choice of 45 minutes corresponds to the maximum effect of local anaesthetics

  24 months

Secondary Outcomes (8)

• - To evaluate the time course and duration of the effectiveness of the nerve blocks on spontaneous pain on a pain intensity scale completed daily by the patient on a self-evaluation booklet up to 14 days after each block.

  24 months

• - Evaluate the effectiveness of blocks on exercise pain

  24 months

• - Directly compare the efficacy of active blocks, i.e. lidocaine and levobupivacaine, on spontaneous and provoked pain (allodynia)

  24 months

• - Evaluate the effectiveness of each block on provoked pain (mechanical allodynia), mechanical, hot and cold pain thresholds and pain area

  24 months

• - Evaluate the effectiveness of each block on the dimensions of neuropathic pain assessed by the NPSI questionnaire

  24 months

Study Arms (3)

lidocaine 20 mg/ml

EXPERIMENTAL

Name (INN and/or speciality) : Lidocaine 20 mg/ml Pharmaceutical form: Injectable Route of administration: Peri-Nervous Dosage for administration: 20ml Duration of treatment: 2 bolus administrations at 14 day intervals

Drug: Lidocaine 20mg/ml

levobupivacaine 1.25 mg/ml

EXPERIMENTAL

Name (INN and/or speciality) : Levobupivacaine (Chirocaine), 1.25 mg/ml Pharmaceutical form: Injectable Route of administration: Peri-Nervous Dosage for administration: 20ml Duration of treatment: 2 bolus administrations at 14 day intervals

Drug: Levobupivacaine Hydrochloride 1.25 MG/ML

Sodium chloride (NaCl) 0.9

PLACEBO COMPARATOR

Name (INN and/or speciality) : Sodium chloride (NaCl) 0.9 Pharmaceutical form: Injectable Route of administration: Peri-Nervous Dosage for administration: 20ml Duration of treatment: 2 bolus administrations at 14 day intervals

Drug: Sodium Chloride 0.9% Inj

Interventions

Lidocaine 20mg/ml DRUG

2 bolus administrations at 14 day intervals Route of administration: Peri-Nervous Dosage for administration: 20ml

lidocaine 20 mg/ml

Levobupivacaine Hydrochloride 1.25 MG/ML DRUG

2 bolus administrations at 14 day intervals Route of administration: Peri-Nervous Dosage for administration: 20ml

levobupivacaine 1.25 mg/ml

Sodium Chloride 0.9% Inj DRUG

2 bolus administrations at 14 day intervals Route of administration: Peri-Nervous Dosage for administration: 20ml

Sodium chloride (NaCl) 0.9

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 years and over with no maximum age (blocks are generally very well tolerated in the very elderly)
• Pain in the upper or lower limb distal enough to be completely covered by a peripheral nerve block
• Chronic pain for at least 6 months
• Ischaemic or haemorrhagic stroke for at least 6 months documented clinically and by appropriate imaging (MRI)
• Post-stroke central neuropathic pain defined as pain occurring in the aftermath of stroke meeting the criteria for probable or defined neuropathic pain according to the NeuPSIG algorithm and with a DN4 screening questionnaire score of at least 4 out of 10.
• Patients affiliated to a social security scheme or beneficiaries of such a scheme
• Acceptance and signing of the informed consent

You may not qualify if:

• Inability or unwillingness to sign an informed consent
• Person subject to a legal protection measure (safeguard of justice, curatorship, guardianship)
• Patients with ongoing psychiatric pathology (major depression, psychosis) or cognitive disorders that prevent a good understanding of the protocol and questionnaires
• Pain that is too widespread in one hemicycle or limb and cannot be adequately covered by blocks
• Ongoing drug or substance abuse
• Language (aphasia) or comprehension disorders, illiteracy
• Moderate to severe renal or hepatic impairment
• Contraindication to local anaesthetics for use in perineural blocks (infection or acute inflammation in the injection area, known allergy).
• Pregnancy or breastfeeding
• Known hypersensitivity to lidocaine, levobupivacaine, amide-linked local anaesthetics or to any of the excipients contained in the specialities used in the study.
• Patients with recurrent porphyria or severe hypotension contraindicating treatment with lidocaine and/or levobupivacaine
• Current treatment with antiarrhythmic drugs causing torsades de pointes (amiodarone, disopyramide, quinidinics, sotalol...) or with antiarrhythmic drugs with local anaesthetic activity (mexiletine or class III antiarrhythmic drugs) and cannot be discontinued.
• Too little pain at the time of the blocks (\< 4 out of 10)
• Need to modify analgesic pharmacological treatment at the beginning or during the study

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (2)

CHU Ambroise Paré

Boulogne-Billancourt, 92100, France

RECRUITING

Hôpital Raymond Poincaré

Garches, 92380, France

RECRUITING

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Interventions

Lidocaine; Levobupivacaine; Sodium Chloride

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Bupivacaine; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

VALERIA MARTINEZ, MD

CONTACT

01 47 10 76 22; valeria.martinez@aphp.fr

NADINE ATTAL, MD

CONTACT

0149095931; nadine.attal@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: It is a randomised, double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Patients will be randomised to receive one of 3 study treatments (lidocaine 20 mg/ml, levobupivacaine 1.25 mg/ml, or saline).

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: June 6, 2024
• Study Start: February 9, 2024
• Primary Completion (Estimated): September 8, 2026
• Study Completion (Estimated): September 8, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

FR (2)