Pain Clinical Trial
— INjECTOfficial title:
BotulInum Toxin Type A for Peripheral Neuropathic Pain in subjEcts With Carpal Tunnel Syndrome: a Multicenter, Randomized, Doubleblind, Placebo-controlled Study
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.
Status | Recruiting |
Enrollment | 164 |
Est. completion date | December 2023 |
Est. primary completion date | December 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility | Inclusion Criteria: 1. Male or female subject aged =18 and =60 years old. 2. Probable or definitive NP according to the International Association for the Study of Pain criteria. 3. 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 4. Moderate-severe pain according to the 11-point Numerical. Rating Scale (NRS; 4-8) 5. 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. 6. Signed informed consent prior to participation in the study Exclusion Criteria: 1. Pain level =9 on 11-point NRS. 2. CTS with atrophy of median-innervated muscles and EMG study suggesting a severe nerve injury. 3. Subject with contraindications or hypersensitivity to BoNT-A. 4. Subject with disorders of the neuromuscular junction, progressive neuropathy disorders, coagulation disorders or major psychiatric disorders. 5. Subject with diabetes, rheumatoid arthritis, connective tissue diseases, vasculitis, untreated hypothyroidism, acromegaly. 6. Subject using drugs acting on neuromuscular junctions, topical drugs (e.g., capsaicin or lidocaine), or anesthetic blocks. 7. Subject has used BoNT-A. 8. Subject is pregnant or breastfeeding women. 9. Subject enrolled in another interventional trial for the treatment of of the same disease. |
Country | Name | City | State |
---|---|---|---|
Italy | Aou Mater Domini | Catanzaro |
Lead Sponsor | Collaborator |
---|---|
Francesco Bono |
Italy,
Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, Raicher I, Üçeyler 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 — View Citation
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. — View Citation
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.2 — View Citation
Brown EA, Schütz 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. Review. — View Citation
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38. Review. — View Citation
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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. Review. — View Citation
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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. Review. — View Citation
Olney RK. Carpal tunnel syndrome: complex issues with a "simple" condition. Neurology. 2001 Jun 12;56(11):1431-2. — View Citation
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 — View Citation
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. Erratum in: Ann Neurol. 2009 Mar;65(3):359. — View Citation
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* Note: There are 17 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | Assessment of the therapeutic gain of BoNT-A in terms of relief of spontaneous pain | Therapeutic gain of the second administration of BoNT-A in terms of relief of spontaneous pain, measured as change in mean weekly average daily pain intensity, measured by the 11-point numerical rating scale (NRS, 0=no pain, 10=maximum pain imaginable) of the BPI , and change in maximum pain in subjects who received two administrations. | 25 weeks | |
Secondary | Assessment of BoNT-A effects in reducing neuropathic symptoms with Bedside Sensory Assessment. | Effects of BoNT-A on
- sensory disturbances and hyperalgesia in response to mechanical punctate and thermal stimuli measured by sensory assessment at the bed side; The subject examined at the bed side describes the sensation after a precise and reproducible stimulus is applied. To assess either a loss (negative sensory signs) or a gain (positive sensory signs) of somatosensory function, the responses are graded as normal, decreased or increased. The stimulus evoked (positive) pain types are classified as hyperalgesic (experiencing increased pain from a stimulus that is normally perceived as less painful) or allodynic (experiencing pain from a stimulus that does not normally trigger a pain response), and according to the dynamic or static character of the stimulus. |
25 weeks | |
Secondary | Assessment of BoNT-A effects in reducing neuropathic symptoms with VAS. | Effects of BoNT-A on
- severity of brush-induced allodynia measured by a brush on the Visual Analogue Scale, a self-reported scale consisting of a horizontal or vertical line, usually 10 centimetres long (100 mm) anchored at the extremes by two verbal descriptors referring to the pain status. |
25 weeks | |
Secondary | Assessment of BoNT-A effects in reducing neuropathic symptoms with the Neuropathic Pain Symptom Inventory . | Effects of BoNT-A on
- neuropathic symptoms (ie, burning pain, deep pain, paroxysmal pain, paraesthesia or dysaesthesia, and allodynia) measured with the Neuropathic Pain Symptom Inventory (NPSI). This questionnaire rates the intensity of five neuropathic dimensions (symptom combinations) during the last 24 hours (burning, deep pain, paroxysmal pain, allodynia/hyperalgesia, paresthesia/dysesthesia) on an 11-point (0-10) numerical scale. |
25 weeks | |
Secondary | Assessment of BoNT-A impact on patient's quality of life. | Impact of BoNT-A treatment on patient's quality of life, measured through Visual Analogue Scale of the 5-level EuroQoL (EQ-5D-5L) from 0 (imaginable health state) to 100 (worst imaginable health state) at baseline and after 24 weeks. | 25 weeks | |
Secondary | Assessment of BoNT-A safety | BoNT-A's overall safety and tolerability will be assessed throughout the study by measuring the occurrence and grade of AEs or serious AEs (SAEs), both registered by the subject in the patient diary or assessed by the physician during the visit(s). All AEs will be identified using MedDRA terms and will be evaluated for intensity and correlation with treatment | 24 weeks |
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