Carpal Tunnel SyndromePhase 2INjECTNCT05411900
BotulInum Toxin Type A for Peripheral Neuropathic Pain in subjEcts With Carpal Tunnel Syndrome
A Phase 2 study testing BoNT-A in people with Carpal Tunnel Syndrome and Neurogenic Inflammation, run by Francesco Bono at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Carpal Tunnel Syndrome, Neurogenic Inflammation, Pain
- What is being tested?
- BoNT-A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 164 participants
- Where
- 1 siteItaly
- Study dates
- 25 May 2022to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Aou Mater Domini
Catanzaro, 88100
Francesco Bono, 09613647269, f.bono@unicz.it
Giuseppe Giuliano, 0961 712 554, direttore.generale@materdominiaou.it
About this study
Official 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.
Read the detailed description
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.
- Being tested
- BoNT-A, Placebo
- Keywords
- Quality of life, Neuropathic Pain, Botulinum toxin type A, Paroxysmal pain, Carpal tunnel syndrome, Safety
- Medical subject headings
- Carpal Tunnel Syndrome, Neurogenic Inflammation, Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BoNT-ADrug
Also called Experimental intervention
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.
PlaceboDrug
Also called Control intervention
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: BoNT-A |
| Control group: Placebo arms | Placebo comparator | Subjects randomized in control group will receive intradermal injections of placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 25 weeks
Secondary outcomes (6)
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.
Measured: 25 weeks
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.
Measured: 25 weeks
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.
Measured: 25 weeks
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.
Measured: 25 weeks
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.
Measured: 25 weeks
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
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2022
- Study start25 May 2022
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Carpal Tunnel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Interventional prospective, multicenter, randomized, double-blind, placebo-controlled study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Francesco Bono
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Francesco Bono, Azienda Ospedaliera Universitaria Mater Domini, Catanzaro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05411900
- Sponsor's protocol ID
- EudraCT number 2021-006048-29
- Acronym
- INjECT
- Status last verified
- May 2022
- First submitted
- 27 May 2022
- Last updated
- 9 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 26947719Bouhassira 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.
PubMed 15030944Brown 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.
PubMed 24641437Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.
PubMed 8080219Colloca 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.
PubMed 28205574Geoghegan 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.
PubMed 15234492Hobson-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.
PubMed 28375915Huskisson EC. Measurement of pain. Lancet. 1974 Nov 9;2(7889):1127-31. doi: 10.1016/s0140-6736(74)90884-8. No abstract available.
PubMed 4139420Levine 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.
PubMed 8245050Marti 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.
PubMed 27435748Middleton SD, Anakwe RE. Carpal tunnel syndrome. BMJ. 2014 Nov 6;349:g6437. doi: 10.1136/bmj.g6437. No abstract available.
PubMed 25378457Mittal 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.
PubMed 26866499Olney 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.
PubMed 11402097Padua 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.
PubMed 27751557Ranoux 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.
PubMed 18546285
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BotulInum Toxin Type A for Peripheral Neuropathic Pain in subjEcts With Carpal Tunnel Syndrome: a Multicenter, Randomized, Doubleblind, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT05411900
- Acronym / sponsor ID
- INjECT / EudraCT number 2021-006048-29
- Keywords
- Quality of life, Neuropathic Pain, Botulinum toxin type A, Paroxysmal pain, Carpal tunnel syndrome, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Francesco BonoUniversity, hospital or other
- Study start
- 25 May 2022 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 9 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Interventional prospective, multicenter, randomized, double-blind, placebo-controlled study.
| Arm | Type | Receives |
|---|---|---|
| Experimental group: BoNT-A arms | Experimental | Drug: BoNT-ASubjects 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. |
| Control group: Placebo arms | Placebo comparator | Drug: PlaceboSubjects randomized in control group will receive intradermal injections of placebo. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BoNT-AAlso: Experimental interventionA 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. | Drug | Experimental group: BoNT-A arms |
| PlaceboAlso: Control interventionPlacebo 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. | Drug | Control group: Placebo arms |
Primary outcome
Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS
Time frame: 25 weeks
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.
Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS
Time frame: 25 weeks
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.
6 secondary outcomes
Assessment of the therapeutic gain of BoNT-A in terms of relief of spontaneous pain
Time frame: 25 weeks
Assessment of BoNT-A effects in reducing neuropathic symptoms with Bedside Sensory Assessment.
Time frame: 25 weeks
Assessment of BoNT-A effects in reducing neuropathic symptoms with VAS.
Time frame: 25 weeks
Assessment of BoNT-A effects in reducing neuropathic symptoms with the Neuropathic Pain Symptom Inventory .
Time frame: 25 weeks
Assessment of BoNT-A impact on patient's quality of life.
Time frame: 25 weeks
Assessment of BoNT-A safety
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2022.
- Results publication: PubMed 26947719Attal 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.
- Results publication: PubMed 15030944Bouhassira 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.
- Results publication: PubMed 24641437Brown 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.
- Results publication: PubMed 8080219Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.
- Results publication: PubMed 28205574Colloca 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.
- Results publication: PubMed 15234492Geoghegan 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.
- Results publication: PubMed 28375915Hobson-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.
- Results publication: PubMed 4139420Huskisson EC. Measurement of pain. Lancet. 1974 Nov 9;2(7889):1127-31. doi: 10.1016/s0140-6736(74)90884-8. No abstract available.
- Results publication: PubMed 8245050Levine 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.
- Results publication: PubMed 27435748Marti 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.
- Results publication: PubMed 25378457Middleton SD, Anakwe RE. Carpal tunnel syndrome. BMJ. 2014 Nov 6;349:g6437. doi: 10.1136/bmj.g6437. No abstract available.
- Results publication: PubMed 26866499Mittal 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BoNT-A in people with Carpal Tunnel Syndrome and Neurogenic Inflammation, run by Francesco Bono at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesco Bono (0961 3647269, f.bono@unicz.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS (time frame: 25 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05411900, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2022.