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

Trigeminal Neuralgia Clinical Trial

Official title:

Safety and Efficacy of Botulinum Toxin A in Patients With Trigeminal Neuralgia: a Double-blind, Randomized, Placebo-controlled, Parallel-group Trial and Investigation of Neuro-inflammatory Biomarkers as Predictors of Efficacy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06315790
• Other study ID #: TN BTX-A Trial
• Status: Recruiting
• Phase: Phase 3
• Start date: November 1, 2023
• Est. completion date: October 1, 2025

Study information

• Verified date: March 2024
• Source: Danish Headache Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neuralgia
• Trigeminal Neuralgia

Intervention

Drug:
• Botulinum toxin A
Subcutaneously injections are given unilaterally in the face at predefined injection sites.

Other:
• Isotonic saline
Subcutaneously injections are given unilaterally in the face at predefined injection sites.

Locations

Country	Name	City	State
Denmark	Danish Headache Center	Glostrup

Sponsors (1)

Lead Sponsor	Collaborator
Henrik Schytz

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pure paroxysmal pain vs. paroxysms with concomitant pain	Patients with purely paroxysmal pain versus patients with concomitant continuous pain.	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Other	Idiopathic vs. classical trigeminal neuralgia	Patients with idiopathic trigeminal neuralgia versus patients with classical trigeminal neuralgia	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Other	Patients with severe pain	Patients with severe pain (defined as ADP =7 ) versus patients with less severe pain (ADP < 7)	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Other	Gender distribution	Male patients versus female patients	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Other	Disease duration	Patients with a long duration of TN (= 5 years) versus patients with a short duration of TN (< 5 years).	Baseline
Primary	Proportion of responders in botulunim toxin A and placebo group	Responders are participants with a 30 % reduction in mean average daily pain score.	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Secondary	Biomarkers	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.	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Secondary	Tear fluid CGRP	The difference in tear fluid calcitonin gene-related peptide (CGRP) between the symptomatic side and the asymptomatic side.	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Secondary	50 % reduction	The proportion of subjects reaching =50% reduction in mean Average Daily Pain (ADP) intensity score	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Secondary	75 % reduction	The proportion of subjects reaching =75% reduction in mean ADP	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Secondary	Prolonged 30 % reduction	The proportion of subjects reaching =30% reduction in mean ADP	Week 9 to 12 compared with baseline (week -4 to -1)
Secondary	Change in paroxysms	Change in mean number of daily pain paroxysms n BTX-A group and placebo group	Evaluation period (week 2 to 5) and during weeks 9 to 12 compared with baseline (week -4 to -1)
Secondary	PGI-C	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	Week 5
Secondary	PENN Facial Pain Scale-Revised (PENN-FPS-R)	Change in the PENN-FPS-R	Baseline to week 5
Secondary	Patient's guess	Proportion of subjects correctly guessing whether they received BTX-A or placebo	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Secondary	Dropouts	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.	Up to 24 weeks
Secondary	Side effects	Proportion of subjects with side-effects registered in weeks 2 to 5 during treatment with BTX-A compared with placebo through study completion.	Up to 24 weeks