Botulinum Toxin for Chronic Neuropathic Pain

Sponsor

Region Zealand (Other)

Overall Status

Recruiting

CT.gov ID

NCT06036043

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Treatment of peripheral neuropathic pain with Botulinum Toxin (BoNT) has showed promising results since the first study was released in 2001. Further research, however, is needed in order to strengthen the treatment, and a number of questions are unanswered. This includes which indication is the treatment the most effective, how should the treatment be administered, what is the duration of the effect? This study is a prospective interventional open label study, designed to assess the efficacy and safety of Botolinum toxin in the treatment of chronic neuropathic pain.

Condition or Disease	Intervention/Treatment	Phase
Neuralgia Chronic Pain	Drug: Botulinum toxin type A

Detailed Description

Background:

There are eight randomized controlled trials investigating the effectiveness of BoNT for peripheral neuropathic pain. The indications in the studies include diabetic neuropathy, post-herpetic neuropathy, and peripheral nerve injury. Overall, the studies indicate a treatment effect that is significantly better than placebo. However, the studies are relatively small, their outcome measures vary, making comparison difficult, and there is considerable variation in the degree of pain reduction. The duration of the effect of BoNT treatment varies greatly and has not been systematically studied. The current evidence provides a promising background in the treatment of BoNT og neuropathic pain, but further research and documentation are needed.

At the Interdisciplinary Pain Center, Zealand University Hospital, BoNT treatment is already used for patients with neuropathic pain, who do not respond to 1. and 2. line treatments. This study will evaluate the efficacy of the treatment.

Method:

The objective of this study is to prospectively follow a one-year cohort and subsequently conduct a follow-up of 7 months (three treatments) for patients initiating BoNT treatment. The follow-up includes monitoring the treatment's effectiveness, duration, and recording adverse reactions.

Study Design

Study Type:

Observational

Anticipated Enrollment :

12 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Botulinum Toxin for Chronic Neuropathic Pain - an Interventional Open Label Study at the Interdisciplinary Pain Center, Zealand University Hospital

Actual Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Intervention group Patients treated with Botulinum Toxin	Drug: Botulinum toxin type A The treatment will be administered either as a) subcutaneous infiltration with BoNT, covering the painful area, identified as allodynia during sensory examination, or b) perineural injection corresponding to the peripheral nerve(s) innervating the area where the pain is localized. 100 IU Xeomin is mixed with 4 ml NaCl. Injections are performed with a 1.5 cm spacing. Maximum of 40 injections (200 IU). 100 IU of botulinum toxin is mixed with 10 ml NaCl. For administration around multiple nerves, 50-100 IU per nerve (maximum 300 IU). The treatment will primarily be provided by the principal investigator, or an anesthesiologist specializing in nerve blocks. The specific method will be determined on an individual basis. If there is no effect after one to two treatments, the treatment will be considered ineffective and discontinued. A treatment interval of 3 months has been established in accordance with a previous larger study. Other Names: Xeomin

Arm

Intervention/Treatment

Intervention group

Patients treated with Botulinum Toxin

Drug: Botulinum toxin type A

The treatment will be administered either as a) subcutaneous infiltration with BoNT, covering the painful area, identified as allodynia during sensory examination, or b) perineural injection corresponding to the peripheral nerve(s) innervating the area where the pain is localized. 100 IU Xeomin is mixed with 4 ml NaCl. Injections are performed with a 1.5 cm spacing. Maximum of 40 injections (200 IU). 100 IU of botulinum toxin is mixed with 10 ml NaCl. For administration around multiple nerves, 50-100 IU per nerve (maximum 300 IU). The treatment will primarily be provided by the principal investigator, or an anesthesiologist specializing in nerve blocks. The specific method will be determined on an individual basis. If there is no effect after one to two treatments, the treatment will be considered ineffective and discontinued. A treatment interval of 3 months has been established in accordance with a previous larger study.

Other Names:

Xeomin

Outcome Measures

Primary Outcome Measures

Maximal pain intensity [At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).]
Proportion of patients with clinically relevant reduction in maximum pain (last 24 hours) compared to baseline, assessed using the Numerical Rating Scale (NRS 0-10; Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible'). A minimal important difference (MID) of NRS 1 is considered as clinically relevant.
pain intensity at rest [At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®)]
Proportion of patients with clinically relevant reduction in average pain at rest (last 24 hours) compared to baseline, assessed using the Numerical Rating Scale (NRS 0-10). A MID of NRS 1 is considered as clinically relevant.
Frequency of serious adverse events [Up to 7 months after initiating treatment]
Frequency of serious adverse events (according to ICH-GCP definition).
Frequency of serious adverse reactions [Up to 7 months after initiating treatment]
Frequency of serious adverse reactions (according to ICH-GCP definition).

Secondary Outcome Measures

EuroQol-5 Dimension (EQ-5D) [At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).]
Change in health-related quality of life (EQ-5D) compared to baseline. EQ-5D includes pain evaluation using the visual analogue scale (VAS 0-100; Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible')
Neuropathic Pain Symptom Inventory (NPSI) [At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).]
Change in neuropathic pain compared to baseline using the NPSI that evaluates 12 different symptoms according to a numerical rating scale from 0 to 10 (Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible')
Onset and duration [At 28 days]
Time from treatment before onset of effect and duration of effect

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Condition of neuropathic pain verified by paraclinical examination or supported by underlying diseases (e.g., diabetes or herpes zoster).
The condition is characterized by allodynia, hyperalgesia, and/or neuralgiform symptoms such as burning and stabbing pain.
The affected area can be identified through objective examination with detection of disturbances in touch using cotton swabs, pin-prick, and/or vibration

Exclusion Criteria:

Mixed etiology of pain not solely attributable to neuropathy (e.g., fibromyalgia and neuropathy or nociceptive pain and neuropathy).
Contraindication to BoNT treatment (allergy to the toxin).
Pregnancy.
Diseases where BoNT treatment is contraindicated, such as motor neuron diseases and muscular dystrophy.
Severe psychiatric disorder.