Clinical trial NCT03066635: Botulinum Toxin Type A Block of the Otic Ganglion in Chronic Cluster Headache: Safety Issues
Official title: Botulinum Toxin Type A Block of the Otic Ganglion in Chronic Cluster Headache: Safety Issues
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cluster Headache
Keywords: Nerve block
Ganglia, Parasympathetic
Botulinum Toxins, Type A
Injection
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
First posted: 2017-02-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cluster headache (CH) is the most common of the trigeminal autonomic cephalalgias and one of the most severe pains known to man, having a large impact on the sufferer's quality of life. A parasympathetic dysfunction in CH has been suggested. The sphenopalatine ganglion has been a target for treatment of primary headache disorders for more than a century but there are several anatomic and physiologic studies that suggest that another cranial parasympathetic ganglion, the otic ganglion (OG), might be also relevant in CH. In this study OG will be blocked with botulinum toxin type A in a pilot study in 10 patients with chronic cluster headache. Recruitment of patients will be solely in Norway. There is no data available to determine the correct dosage of botulinum toxin. A similar neural structure that has been blocked with botulinum toxin in humans is the sphenopalatine ganglion. The investigators injected 10 patients suffering from intractable chronic cluster headache with botulinum toxin in the sphenopalatine ganglion. 5 patients were given 25 IU and 5 patients were given 50 IU. Even though the number of treated patients is low, there did not appear to be differences in the adverse events profile between those who received 25 Iu and those who received 50 IU. The investigators also previously injected 25 IU botulinum toxin towards the sphenopalatine ganglion bilaterally (i.e. 25 IU in each side) in 10 patients suffering from intractable chronic migraine. Doses of up to 25 IU have been injected in structures adjacent to the otic ganglion, for instance in dystonia towards the lateral pterygoid muscle. Thus it was decided for this study on injection towards the otic ganglion, to explore the safety of 12.5 and 25 IU of botulinum toxin.


Eligibility criteria: Inclusion Criteria:

* Informed and written consent
* Fulfilling International Classification of Headache Disorders (ICHD) -3 Beta criteria for chronic cluster headache
* Mean attack frequency of four attacks per week or more
* Agreeing to refrain from starting new prophylactic cluster headache medication, including steroids, or any other therapy aimed at cluster headache, and agreeing to maintain existing prophylactic cluster headache medication from 4 weeks before entering the baseline period throughout the duration of the study
* Intractable cluster headache, i.e. unsatisfactory effect, intolerable side effects or contraindication of at least 2 of the following medications: Verapamil, Lithium, Suboccipital steroid injection,
* Able to distinguish between cluster headache attacks and other types of headache.

Exclusion Criteria:

* Modification or addition of any prophylactic drug dose used against cluster headache in the last 4 weeks before inclusion of during the trial
* Use of antipsychotic medication in the last 4 weeks before inclusion
* Concomitant significant heart or lung disease
* Systemic or local conditions which can increase the risk of the procedure
* Psychiatric or psychological conditions interfering with the participation in the study
* Pregnancy
* Breast feeding
* Inadequate use of contraceptives
* Opioid overuse
* Abuse of drugs including alcohol
* Anatomical variants which might impede the study treatment
* Known hypersensitivity to botulinum toxin type A or any of the excipients found in Botox
* Current treatment with drugs that interact with botulinum toxin: aminoglycosides, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing agents (tubocurarine derivates), lincosamides, polymyxins, quinidine, magnesium sulfate or anticholinesterases.
* Previous cerebral ischemic infarction
* Not able to take magnetic resonance imaging (MRI)
* Previous destructive surgery of interventional procedures involving the C2 and C3 roots (vertebrae), sphenopalatine ganglion, any extracranial nerve, trigeminal nerve, or deep brain stimulation.

Primary outcomes:
measure: Number of adverse events (AE)
timeFrame: for the follow-up period of 6 months
Secondary outcomes:
measure: Number of cluster headache attacks per week
timeFrame: for the follow-up period of 6 months
measure: Duration of cluster headache attacks
timeFrame: for the follow-up period of 6 months
measure: Days without cluster headache attacks
timeFrame: for the follow-up period of 6 months
measure: Headache intensity on a 0-5 scale
timeFrame: for the follow-up period of 6 months
measure: Mean intensity per attack
timeFrame: for the follow-up period of 6 months
measure: Mean number of attacks with intensity grade 4-5
timeFrame: for the follow-up period of 6 months
measure: Functional level
timeFrame: for the follow-up period of 6 months
measure: Triptan use per 4 weeks
timeFrame: for the follow-up period of 6 months
measure: Number of analgesic doses per 4 weeks
timeFrame: for the follow-up period of 6 months
measure: Absenteeism due to cluster headache
timeFrame: for the follow-up period of 6 months
measure: disability
timeFrame: for the follow-up period of 6 months
measure: Occurrence of autonomic symptoms
timeFrame: for the follow-up period of 6 months
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: Department of Neuroscience, Norwegian University of Science and Technology
Study officials:
affiliation: Norwegian University of Science and Technology
name: Lars Jacob Stovner, prof MD
role: STUDY_DIRECTOR
References:
citation: Crespi J, Bratbak D, Dodick DW, Matharu M, Solheim O, Gulati S, Berntsen EM, Tronvik E. Open-Label, Multi-Dose, Pilot Safety Study of Injection of OnabotulinumtoxinA Toward the Otic Ganglion for the Treatment of Intractable Chronic Cluster Headache. Headache. 2020 Sep;60(8):1632-1643. doi: 10.1111/head.13889. Epub 2020 Jun 25.