Using Botox to treat chronic cluster headaches

Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache

This study is testing if Botox can help people with chronic cluster headaches who haven't found relief from other treatments.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Norwegian University of Science and Technology (Academic / other)
• Locations: 5 sites (Hamburg and 4 other locations)
• Trial ID: NCT03944876 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of botulinum toxin type A in blocking the sphenopalatine ganglion to alleviate chronic cluster headaches in patients who have not responded to other treatments. The study employs a randomized, placebo-controlled, triple-blinded design to ensure unbiased results. Participants will receive either the botulinum toxin or a placebo while maintaining their current headache medication regimen. The aim is to determine if this targeted approach can provide relief from the debilitating pain associated with chronic cluster headaches.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-85 who experience chronic cluster headaches and have not responded adequately to standard pharmacological treatments.

Not a fit: Patients who do not have chronic cluster headaches or those who have not experienced treatment-refractory symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new, effective option for patients suffering from chronic cluster headaches who have not found relief with existing therapies.

How similar studies have performed: Previous phase 1 and phase 2 studies have shown promising results for similar approaches using botulinum toxin for chronic cluster headaches.

Eligibility criteria

Inclusion Criteria:

1. Informed and written consent.
2. Male or female, 18-85 years of age
3. Headache attacks fulfilling the International Classification of Headache Disorders (ICHD) III criteria for chronic cluster headache (CCH) 3.1.2.
4. Dominant headache laterality with ≥ 80% of cluster headache attacks on one side.
5. Subject reports an average of ≥ 4 cluster attacks/week on the side of their dominant headache laterality in the 3 months prior to inclusion and in the baseline period.
6. The condition is pharmacologically refractory defined as suboptimal effect or intolerable side effects or contraindication for verapamil or lithium or suboccipital steroid injection.
7. Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
8. Subject is able to differentiate concomitant headaches from cluster headache.
9. In case of women of childbearing potential (WOCBP) they have to be using highly effective contraception in a period of 4 weeks after injection.
10. Ability to understand study procedures and to comply with them for the entire length of the study

Exclusion Criteria:

1. Subject has had a change in type, dosage or dose frequency of preventive headache medications ≥ two weeks prior to baseline/screening or 5 half-lives, whichever is longer.
2. Subject currently treated with occipital nerve stimulation, deep brain stimulation or other implantable device, that have changed parameters in the last month, or are unable to keep parameters stable throughout the study.
3. Current or previous treatment with implanted medical devices targeting the SPG
4. Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration.
5. Non-responder to both oxygen and triptan.
6. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study drug administration or 5 half-lives, whichever is longer.
7. Subject is currently participating or has participated in the last 3 months in another clinical study in which the subject has, is, or will be exposed to an investigational or non-investigational drug or device.
8. Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
9. Abuse of drugs or alcohol.
10. Use of opioids for ≥10 days per month.
11. Treatment with pharmacological substances that may interact with BTA (aminoglycosids, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), lincosamides, polymyxins, quinidine, magnesium sulfate or anticholinestases.).
12. WOCBP that do not adhere to the requirements for HEC, as noted in inclusion criteria 9 and outlined in section 3.3.
13. Pregnancy or breastfeeding in the study period
14. Subject has undergone facial surgery in the area of the pterygopalatine fossa or zygomaticomaxillary buttress ipsilateral to the planned injection site that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
15. Facial anomaly or trauma which renders the procedure difficult.2
16. Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
17. Subject has been diagnosed with any major infectious processes such as osteomyelitis, or primary or secondary malignancies involving the face that have been active or required treatment in the past 6 months.
18. Patients exhibiting a high degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator.
19. Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator.
20. Patient with active infectious disease or infections that warrants special infection control measures, such as human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
21. Patient with disorders that are known contraindication for Botox® treatment, especially neuromuscular disorders such as motorneuron disorders and myasthenic syndromes
22. Subject has had previous radiofrequency ablation, balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the ipsilateral trigeminal ganglion or any branch of the trigeminal nerve.
23. Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the ipsilateral SPG.
24. Subject has had blocks of short-acting anaesthetics of the ipsilateral SPG in the last 3 months.
25. Subject has undergone onabotulinumtoxinA injections of the head and/or neck in the last 3 months.
26. Subject is anticipated to require any excluded medication, device, or procedure during the study.
27. Subject has a history of bleeding disorders and in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
28. Subject has a history of coagulopathy.
29. Subject is unable to stop antithrombotic medication, eg. anticoagulants and/or antiplatelet therapy, before procedure.
30. The subject has been diagnosed with another trigeminal autonomic cephalalgia or trigeminal neuralgia.
31. The patient cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons:

    * mentally or legally incapacitated or unable to give consent for any reason.
    * in custody due to an administrative or a legal decision, under tutelage, or being admitted to a sanatorium or social institution.
32. The patient is a study centre employee who is directly involved in the study or the relative of such an employee.

Where this trial is running

Hamburg and 4 other locations

• Praxisklinik Ulmenhof — Hamburg, Germany (Recruiting)
• Fondazione IRCCS Istituto Neurologico Carlo Besta (CBNI) — Milan, Italy (Recruiting)
• St Olavs Hospital — Trondheim, Norway (Recruiting)
• Department of Neurology, University Clinic Hospital. Catholic University of Valencia — Valencia, Spain (Recruiting)
• National Hospital of Neurology and Neurosurgery, University College of London — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Tore Wergeland Meisingset, md phd

Conditions Cluster Headache; Botulinum Toxin Type A; Sphenopalatine Ganglion Block; Autonomic Nerve Block; Injections