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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Trigeminal Neuralgia
• Intervention / Treatment: Other: Isotonic saline; Drug: Botulinum toxin A

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Recruiting
    • Danish Headache Center
    • Contact: Henrik Schytz, MD; Phone Number: +4528761824; Email: henrik.winther.schytz.01@regionh.dkonh.dk
    • Principal Investigator: Henrik Schytz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Botulinum toxin A	Drug: Botulinum toxin A; Subcutaneously injections are given unilaterally in the face at predefined injection sites.
Placebo Comparator: Isotonic saline	Other: Isotonic saline; Subcutaneously injections are given unilaterally in the face at predefined injection sites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
Prolonged 30 % reduction	The proportion of subjects reaching ≥30% reduction in mean ADP	Week 9 to 12 compared with baseline (week -4 to -1)
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)
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
PENN Facial Pain Scale-Revised (PENN-FPS-R)	Change in the PENN-FPS-R	Baseline to week 5
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)
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
Gender distribution	Male patients versus female patients	Evaluation period (week 2 to 5) compared with baseline (week -4 to -1)
Disease duration	Patients with a long duration of TN (≥ 5 years) versus patients with a short duration of TN (< 5 years).	Baseline

Collaborators and Investigators

• Sponsor: Henrik Schytz

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: August 28, 2023
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Stomatognathic Diseases; Mouth Diseases; Peripheral Nervous System Diseases; Cranial Nerve Diseases; Facial Nerve Diseases; Trigeminal Nerve Diseases; Facial Neuralgia; Neuralgia; Trigeminal Neuralgia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: TN BTX-A Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No