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

NCT ID: NCT05411900

Last Updated: 2022-06-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

164 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-25

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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Botulinum toxin type A (BoNT-A) is widely used to treat muscle hyperactivity, based on its ability to inhibit synaptic exocytosis and, therefore, to disable neural transmission. Further research has shown that BoNT-A has analgesic properties independently from its action on muscle tone, possibly by acting on neurogenic inflammation. Animal studies indeed showed that botulinum neurotoxin can alter and alleviate NP in animals through several mechanisms, including blocking the release of pain mediators, decreasing local inflammation around nerve terminals, deactivating sodium channels, inhibiting the discharge of muscle spindles and decreasing sympathetic transmission.

Evidence on the use of BoNT-A in CTS and occipital neuralgia is still limited as it derives from small patient studies with controversial results, and is therefore considered still insufficient to determine whether or not BoNT-A could be part of the therapeutic arsenal against these NPs (level U). Overall, according to the litterature, the results of BoNT-A injections on NP are variable, as it seems to be effective in postherpetic neuralgia (evidence level A), may be effective in trigeminal neuralgia and post-traumatic neuralgia (level B) and is possibly effective in diabetic polyneuropathy (level C).

In this multicenter, randomized, double-blinding, placebo-controlled, parallel study it will enroll 164 subjects, both genders, aged ≥18 and ≤60 years old, to obtain 164 overall valuable subjects (23/24 for each center). The recruitment period (V1) will last 1 week after the baseline assessment, eligible subjects will be randomly assigned (1:1) to BoNT-A or placebo arm and will receive the first round of injections. After 12 week ±4 days (V2) subjects will undergo the second treatment round, receiving either a second BoNT-A administration or a second placebo administration. In week 24 ±4 days (V3) the same assessment scheduled for visit 1 will be repeated.

Benefit Assessment :

As described previously, BoNT-A showed some significant advantages over NPs existing treatments, such as the extended duration of its analgesic effects; 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 Carpal Tunnel Syndrome.

Risk Assessment :

Since it has been shown that BoNT-A has a clinically acceptable safety profile, there are no specific risks to this study.

However, considering that the drug has never been tested on patients with carpal tunnel syndrome, the objective of the study also includes the evaluation of its safety in the context of this disease.

Primary Objective

\- The main objective of the study is to assess the efficacy and safety of two successive intradermal administrations of several injections of BoNT-A versus placebo, administered 12 weeks apart, in subjects with CTS and NP Secondary Objectives

The secondary objectives of this study include:

* Assessment of the therapeutic gain of BoNT-A in terms of relief of spontaneous pain.
* Assessment of BoNT-A effects in reducing neuropathic symptoms.
* Assessment of BoNT-A impact on patient's quality of life.
* Assessment of BoNT-A safety and tolerability

Statistical Hypotheses A sample size of 82 participants per group (164 participants overall) would be needed for 90% power to detect a mean difference in pain intensity between groups of 0.7 units (SD=1.3) in a two-sample two tailed t test with a type I error of 0.05, including a 10% of dropout rate. Changes in primary and secondary outcome measures (quantified measures of deficits and pains, pain scores, symptoms, quality of life) will be expressed as differences between baseline and the values obtained at each time point and will be analyzed using a generalized linear mixed-model repeated measures. For all the pre specified endpoints, the analysis will be performed in the intent-to treat population with both the last observation carried forward approach (primary analysis) and observed data (additional analysis- sensitivity). Safety data will be tabulated and where appropriate, analyzed using descriptive statistics. All tests will be two sided and a p-value of less than 0.05 will be considered as statistically significant.

Conditions

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Carpal Tunnel Syndrome Neurogenic Inflammation Pain Drug Use Neuropathic Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Interventional prospective, multicenter, randomized, double-blind, placebo-controlled study.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
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.

Study Groups

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Experimental group: BoNT-A arms

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.

Group Type EXPERIMENTAL

BoNT-A

Intervention Type 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.

Control group: Placebo arms

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

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BoNT-A

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Other Intervention Names

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Experimental intervention Control intervention

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Francesco Bono

OTHER

Sponsor Role lead

Responsible Party

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Francesco Bono

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Aou Mater Domini

Catanzaro, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Francesco Bono

Role: CONTACT

0961 3647269

Facility Contacts

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Francesco Bono

Role: primary

09613647269

Giuseppe Giuliano

Role: backup

0961 712 554

References

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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.

Reference Type RESULT
PMID: 26947719 (View on PubMed)

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.

Reference Type RESULT
PMID: 15030944 (View on PubMed)

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.

Reference Type RESULT
PMID: 24641437 (View on PubMed)

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

Reference Type RESULT
PMID: 8080219 (View on PubMed)

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.

Reference Type RESULT
PMID: 28205574 (View on PubMed)

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.

Reference Type RESULT
PMID: 15234492 (View on PubMed)

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.

Reference Type RESULT
PMID: 28375915 (View on PubMed)

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

Reference Type RESULT
PMID: 4139420 (View on PubMed)

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.

Reference Type RESULT
PMID: 8245050 (View on PubMed)

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.

Reference Type RESULT
PMID: 27435748 (View on PubMed)

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

Reference Type RESULT
PMID: 25378457 (View on PubMed)

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.

Reference Type RESULT
PMID: 26866499 (View on PubMed)

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.

Reference Type RESULT
PMID: 11402097 (View on PubMed)

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.

Reference Type RESULT
PMID: 27751557 (View on PubMed)

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.

Reference Type RESULT
PMID: 18546285 (View on PubMed)

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.

Reference Type RESULT
PMID: 18003941 (View on PubMed)

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.

Reference Type RESULT
PMID: 18289791 (View on PubMed)

Other Identifiers

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EudraCT number 2021-006048-29

Identifier Type: -

Identifier Source: org_study_id

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