Safety and Efficacy of Botulinum Toxin A in Patients With Trigeminal Neuralgia

Phase 3

Recruiting

• Conditions: Trigeminal Neuralgia
• Interventions: Other: Isotonic saline; Drug: Botulinum toxin A

• Registration Number: NCT06315790
• Lead Sponsor: Henrik Schytz

Brief Summary

This is a double-blind randomized clinical trial comparing the pain reduction of individuals treated with BTX-A and placebo as well as evaluating possible changes in neuroinflammatory biomarkers. The trial lasts 16 weeks, with a 4-week baseline phase and a 12-week randomization phase. Four visits are planned: 1) Introduction and baseline data collection, 2) Medical evaluation and treatment assignment, 3) Follow-up with biomarker analysis, and 4) Trial conclusion interview. 80 participants will be included and randomized 1:1.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-28
• Study Start: 2023-11-01
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-11
• Last Update Submitted: 2024-03-11
• Study First Posted: 2024-03-18
• Last Update Posted: 2024-03-18
• Primary Completion: 2025-10-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. A diagnosis of classical TN or idiopathic TN according to criteria of The International Classification of Headache Disorders 3rd edition.
2. Age between 18 and 85 years.
3. Subjects must experience pain defined as a minimum of three TN related pain paroxysms per day at least four days a week of an average intensity of 4 to 10, inclusive, on the 11-point NRS (0 = no pain; 10 = maximum pain imaginable) during the last 4 weeks to enter the baseline phase.
4. During baseline phase subjects must experience pain defined as a minimum of three TN related pain paroxysms per day at least four days a week of an intensity of an average 4 to 10, inclusive, on the 11-point NRS (0= no pain; 10= maximum pain imaginable) during the last month to enter the treatment phase (to be randomized).
5. Fluency in Danish.

Exclusion Criteria

1. Severe cardiovascular and cerebrovascular disease such as ischemic heart disease, myocardial infarction or previous stroke or transient ischemic attack, major CVD interventions during the last three months.
2. Expected poor compliance, i.e., considered unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge.
3. Ongoing and unstable severe psychiatric disease.
4. Anamnestic or clinical symptoms of any kind that are deemed relevant for study participation by the physician who examines the patient.
5. Change of TN treatment or treatment dose within two weeks prior to the baseline visit.
6. Previous treatment with BTX-A for facial pain.
7. Loading treatment within 4 weeks with phenytoin or sodium valproate.
8. Female subjects either pregnant, breastfeeding or with planned conception within the study period.
9. Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during the study.
10. Known allergy to any component of BTX-A.
11. Infection at the proposed injection site.
12. Known severe neuromuscular disorders or any degree of disorder affecting the neuromuscular transmission.
13. Known comprised respiratory function.
14. Member of investigational site staff or relative of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Isotonic saline	Isotonic saline	-
Botulinum toxin A	Botulinum toxin A	-

Primary Outcome Measures

Name	Time	Method
Proportion of responders in botulunim toxin A and placebo group	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)	Responders are participants with a 30 % reduction in mean average daily pain score.

Secondary Outcome Measures

Name	Time	Method
Biomarkers	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)	The degree of concentration change in inflammatory biomarkers (CGRP, CRP, TNF alpha, IL1, IL2, and IL6) in responders versus non-responders in BTX-A and placebo group.
50 % reduction	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)	The proportion of subjects reaching ≥50% reduction in mean Average Daily Pain (ADP) intensity score
Dropouts	Up to 24 weeks	Proportion of dropouts caused by increased intake of trigeminal neuralgia (TN) medication or use of rescue medication in BTX-A group compared to the placebo group through study completion.
75 % reduction	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)	The proportion of subjects reaching ≥75% reduction in mean ADP
Prolonged 30 % reduction	Week 9 to 12 compared with baseline (week -4 to -1)	The proportion of subjects reaching ≥30% reduction in mean ADP
Change in paroxysms	Evaluation period (week 2 to 5) and during weeks 9 to 12 compared with baseline (week -4 to -1)	Change in mean number of daily pain paroxysms n BTX-A group and placebo group
Tear fluid CGRP	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)	The difference in tear fluid calcitonin gene-related peptide (CGRP) between the symptomatic side and the asymptomatic side.
PGI-C	Week 5	Proportion of subjects with a Patient Global Impression of Change (PGI-C) scale response of "much improved" or "very much improved" in BTX-A and placebo group
PENN Facial Pain Scale-Revised (PENN-FPS-R)	Baseline to week 5	Change in the PENN-FPS-R
Patient's guess	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)	Proportion of subjects correctly guessing whether they received BTX-A or placebo
Side effects	Up to 24 weeks	Proportion of subjects with side-effects registered in weeks 2 to 5 during treatment with BTX-A compared with placebo through study completion.

Trial Locations

Locations (1)

Danish Headache Center; 🇩🇰 Glostrup, Denmark