BotulInum Toxin Type A for Peripheral Neuropathic Pain in subjEcts With Carpal Tunnel Syndrome

NCT05411900 | Unknown Phase 2

• 1 other identifier: EudraCT number 2021-006048-29
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of the study is to assess the safety and efficacy of repeated administrations of BoNT-A in subjects with NP attributable to carpal tunnel syndrome (CTS) through a randomized, double-blind, placebo-controlled study. Further research has shown that BoNT-A has analgesic properties independently from its action on muscle tone, possibly by acting on neurogenic inflammation. Therefore, the study drug may be better than other treatments surgical or non-surgical currently available for the treatment of CTS.

Conditions

Carpal Tunnel Syndrome; Neurogenic Inflammation; Pain; Drug Use; Neuropathic Pain

Keywords

Quality of life; Neuropathic Pain; Botulinum toxin type A; Paroxysmal pain; Carpal tunnel syndrome; Safety

Outcome Measures

Primary Outcomes (2)

• Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS

  The primary outcome is mesured as: -Change in mean weekly self-reported average daily pain intensity (mean pain over the past 24 hours recorded every morning in patient's diary during a week) measured by the 11-point numerical rating scale (NRS, 0=no pain, 10=maximum pain imaginable) of the brief pain inventory (BPI) from baseline (one week before randomisation) to 24 weeks after the first administration.

  25 weeks

• Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS

  The primary outcome is mesured as: \- Change in weekly self-reported maximum daily pain intensity (maximum pain intensity over the past 24 hours recorded every morning in patient's diary) measured by the 11-point NRS (NRS, 0=no pain, 10=maximum pain imaginable) of the BPI from baseline (1 week before randomisation) to 24 weeks after the first administration.

  25 weeks

Secondary Outcomes (6)

• Assessment of the therapeutic gain of BoNT-A in terms of relief of spontaneous pain

  25 weeks

• Assessment of BoNT-A effects in reducing neuropathic symptoms with Bedside Sensory Assessment.

  25 weeks

• Assessment of BoNT-A effects in reducing neuropathic symptoms with VAS.

  25 weeks

• Assessment of BoNT-A effects in reducing neuropathic symptoms with the Neuropathic Pain Symptom Inventory .

  25 weeks

• Assessment of BoNT-A impact on patient's quality of life.

  25 weeks

Study Arms (2)

Experimental group: BoNT-A arms

EXPERIMENTAL

Subjects randomized in experimental group will receive intradermal injections of BoNT-A into the wrist and skin area of the hand where the pain is located.

Drug: BoNT-A

Control group: Placebo arms

PLACEBO COMPARATOR

Subjects randomized in control group will receive intradermal injections of placebo.

Drug: Placebo

Interventions

BoNT-A DRUG

A vial of 500 units of BoNT-A will be reconstituted with 2 mL of saline solution (0.9%) and 1 mL of lidocaine solution (2%) to obtain a final concentration of BoNT-A of 166.6 units/mL. Injections will be repeated at sites 1-1.5 cm apart (0.1 ml, 16.6 units per site), up to 20 sites (333 units). To reduce pain caused by the injection, lidocaine and prilocaine cream will be applied to the skin area 60 min before the procedure. Additionally, ice could be applied for a few seconds (4-8) before each injection of 16.6 units of BoNT-A. Injections will be repeated at week 0 and week 12. The active treatment and placebo solutions will be transparent and indistinguishable to maintain treatment blindness.

Also known as: Experimental intervention

Experimental group: BoNT-A arms

Placebo DRUG

Placebo will consist of equal volume of saline solution (0.9%). Injections will be repeated at sites 1-1.5 cm apart (0.1 ml, 16.6 units per site), up to 20 sites (333 units). To reduce pain caused by the injection, lidocaine and prilocaine cream will be applied to the skin area 60 min before the procedure. Additionally, ice could be applied for a few seconds (4-8) before each injection. Injections will be repeated at week 0 and week 12. The active treatment and placebo solutions will be transparent and indistinguishable to maintain treatment blindness.

Also known as: Control intervention

Control group: Placebo arms

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subject aged ≥18 and ≤60 years old.
• Probable or definitive NP according to the International Association for the Study of Pain criteria.
• Daily pain attributable to CTS for at least 6 months. This must be attributable to idiopathic carpal tunnel syndrome and with nerve conduction velocity findings consistent with this condition
• Moderate-severe pain according to the 11-point Numerical. Rating Scale (NRS; 4-8)
• We allow the concomitant use of analgesic treatments if they have been used at a stable doses for 4 weeks before the enrolment and for the whole study.
• Signed informed consent prior to participation in the study

You may not qualify if:

• Pain level ≥9 on 11-point NRS.
• CTS with atrophy of median-innervated muscles and EMG study suggesting a severe nerve injury.
• Subject with contraindications or hypersensitivity to BoNT-A.
• Subject with disorders of the neuromuscular junction, progressive neuropathy disorders, coagulation disorders or major psychiatric disorders.
• Subject with diabetes, rheumatoid arthritis, connective tissue diseases, vasculitis, untreated hypothyroidism, acromegaly.
• Subject using drugs acting on neuromuscular junctions, topical drugs (e.g., capsaicin or lidocaine), or anesthetic blocks.
• Subject has used BoNT-A.
• Subject is pregnant or breastfeeding women.
• Subject enrolled in another interventional trial for the treatment of of the same disease.

Sponsors & Collaborators

• Francesco Bono: lead

Study Sites (1)

Aou Mater Domini

Catanzaro, 88100, Italy

RECRUITING

Related Publications (17)

• Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, Raicher I, Uceyler N, Sommer C, Bouhassira D. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016 May;15(6):555-65. doi: 10.1016/S1474-4422(16)00017-X. Epub 2016 Mar 2.

  PMID: 26947719 RESULT

• Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004 Apr;108(3):248-257. doi: 10.1016/j.pain.2003.12.024.

  PMID: 15030944 RESULT

• Brown EA, Schutz SG, Simpson DM. Botulinum toxin for neuropathic pain and spasticity: an overview. Pain Manag. 2014 Mar;4(2):129-51. doi: 10.2217/pmt.13.75.

  PMID: 24641437 RESULT

• Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.

  PMID: 8080219 RESULT

• Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, Freeman R, Truini A, Attal N, Finnerup NB, Eccleston C, Kalso E, Bennett DL, Dworkin RH, Raja SN. Neuropathic pain. Nat Rev Dis Primers. 2017 Feb 16;3:17002. doi: 10.1038/nrdp.2017.2.

  PMID: 28205574 RESULT

• Geoghegan JM, Clark DI, Bainbridge LC, Smith C, Hubbard R. Risk factors in carpal tunnel syndrome. J Hand Surg Br. 2004 Aug;29(4):315-20. doi: 10.1016/j.jhsb.2004.02.009.

  PMID: 15234492 RESULT

• Hobson-Webb LD, Juel VC. Common Entrapment Neuropathies. Continuum (Minneap Minn). 2017 Apr;23(2, Selected Topics in Outpatient Neurology):487-511. doi: 10.1212/CON.0000000000000452.

  PMID: 28375915 RESULT

• Huskisson EC. Measurement of pain. Lancet. 1974 Nov 9;2(7889):1127-31. doi: 10.1016/s0140-6736(74)90884-8. No abstract available.

  PMID: 4139420 RESULT

• Levine DW, Simmons BP, Koris MJ, Daltroy LH, Hohl GG, Fossel AH, Katz JN. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am. 1993 Nov;75(11):1585-92. doi: 10.2106/00004623-199311000-00002.

  PMID: 8245050 RESULT

• Marti C, Hensler S, Herren DB, Niedermann K, Marks M. Measurement properties of the EuroQoL EQ-5D-5L to assess quality of life in patients undergoing carpal tunnel release. J Hand Surg Eur Vol. 2016 Nov;41(9):957-962. doi: 10.1177/1753193416659404. Epub 2016 Jul 20.

  PMID: 27435748 RESULT

• Middleton SD, Anakwe RE. Carpal tunnel syndrome. BMJ. 2014 Nov 6;349:g6437. doi: 10.1136/bmj.g6437. No abstract available.

  PMID: 25378457 RESULT

• Mittal SO, Safarpour D, Jabbari B. Botulinum Toxin Treatment of Neuropathic Pain. Semin Neurol. 2016 Feb;36(1):73-83. doi: 10.1055/s-0036-1571953. Epub 2016 Feb 11.

  PMID: 26866499 RESULT

• Olney RK. Carpal tunnel syndrome: complex issues with a "simple" condition. Neurology. 2001 Jun 12;56(11):1431-2. doi: 10.1212/wnl.56.11.1431. No abstract available.

  PMID: 11402097 RESULT

• Padua L, Coraci D, Erra C, Pazzaglia C, Paolasso I, Loreti C, Caliandro P, Hobson-Webb LD. Carpal tunnel syndrome: clinical features, diagnosis, and management. Lancet Neurol. 2016 Nov;15(12):1273-1284. doi: 10.1016/S1474-4422(16)30231-9. Epub 2016 Oct 11.

  PMID: 27751557 RESULT

• Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008 Sep;64(3):274-83. doi: 10.1002/ana.21427.

  PMID: 18546285 RESULT

• Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008 Apr 29;70(18):1630-5. doi: 10.1212/01.wnl.0000282763.29778.59. Epub 2007 Nov 14.

  PMID: 18003941 RESULT

• Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D. Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion? Pain. 2008 Aug 31;138(2):343-353. doi: 10.1016/j.pain.2008.01.006. Epub 2008 Mar 4.

  PMID: 18289791 RESULT

MeSH Terms

Conditions

Carpal Tunnel Syndrome; Neurogenic Inflammation; Pain; Neuralgia

Interventions

incobotulinumtoxinA

Condition Hierarchy (Ancestors)

Median Neuropathy; Mononeuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Nerve Compression Syndromes; Cumulative Trauma Disorders; Sprains and Strains; Wounds and Injuries; Neurologic Manifestations; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Central Study Contacts

Francesco Bono

CONTACT

0961 3647269; f.bono@unicz.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: To maintain the blinding of the study drug (BoNT-A or placebo), all study personnel will be blinded to subjects' treatment assignment. Physicians, nurses, subjects, and any study personnel performing assessments must NOT be informed of the subject's treatment assignment except in the event of a medical emergency or as required by regulatory authorities. The injection syringes will be prepared by pharmacy personnel not involved in the study to ensure that the clinical site staff responsible for administering the study drug and conducting assessments per the protocol, and the subject, remain blinded to study treatment. Moreover, the BoNT-A and placebo solution will be limpid and indistinguishable, to maintain blindness. Both subjects, investigators and study personnel will maintain blindness to the treatments throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Interventional prospective, multicenter, randomized, double-blind, placebo-controlled study.

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 9, 2022
• Study Start: May 25, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: June 9, 2022

Record last verified: 2022-05

Locations

IT (1)