Botulinum Toxin Type A Block of the Otic Ganglion in Chronic Cluster Headache: Safety Issues

June 17, 2021 updated by: Norwegian University of Science and Technology
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Trondheim, Norway
        • Department of Neuroscience, Norwegian University of Science and Technology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Botulinum Toxin 25 IU
5 patients will be injected with 25 IU of Botulinum Toxin Type A towards the otic ganglion in the symptomatic side (ipsilateral to the pain)
Drug: Botulinum Toxin Type A 25 IU
injection with 25 IU botulinum toxin towards the otic ganglion (symptomatic side) using image-guided navigation and the MultiGuide device
Other Names:
  • Botox
  • Allergan
  • BTA
EXPERIMENTAL: Botulinum Toxin 12.5 IU
5 patients will be injected with 12.5 IU of Botulinum Toxin Type A towards the otic ganglion in the symptomatic side (ipsilateral to the pain)
Drug: Botulinum Toxin Type A 12.5 IU
injection with 12.5 IU botulinum toxin towards the otic ganglion (symptomatic side) using image-guided navigation and the MultiGuide device
Other Names:
  • Botox
  • Allergan
  • BTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse events (AE)
Time Frame: for the follow-up period of 6 months
All adverse events will be registered. The likelihood of a relationship between the AE and the pharmacological substance or the procedure will be evaluated. Data will be collected from the headache diary (free text) and open questions at the office follow up visits.
for the follow-up period of 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of cluster headache attacks per week
Time Frame: for the follow-up period of 6 months
Number of cluster headache attacks per week
for the follow-up period of 6 months
Duration of cluster headache attacks
Time Frame: for the follow-up period of 6 months
Duration of cluster headache attacks
for the follow-up period of 6 months
Days without cluster headache attacks
Time Frame: for the follow-up period of 6 months
number of days without cluster headache attacks
for the follow-up period of 6 months
Headache intensity on a 0-5 scale
Time Frame: for the follow-up period of 6 months
The headache intensity is registered in the headache diary using a scale from 0-5
for the follow-up period of 6 months
Mean intensity per attack
Time Frame: for the follow-up period of 6 months
The headache intensity is registered in the headache diary using a scale from 0-5
for the follow-up period of 6 months
Mean number of attacks with intensity grade 4-5
Time Frame: for the follow-up period of 6 months
Mean number of attacks with intensity grade 4-5
for the follow-up period of 6 months
Functional level
Time Frame: for the follow-up period of 6 months
The functional level will be assessed by the WHO Performance Status
for the follow-up period of 6 months
Triptan use per 4 weeks
Time Frame: for the follow-up period of 6 months
Triptan use per 4 weeks during the whole duration of the study
for the follow-up period of 6 months
Number of analgesic doses per 4 weeks
Time Frame: for the follow-up period of 6 months
the number of analgesic doses per 4 weeks during the whole duration of the study
for the follow-up period of 6 months
Absenteeism due to cluster headache
Time Frame: for the follow-up period of 6 months
Absenteeism due to cluster headache as assessed by the headache diary
for the follow-up period of 6 months
disability
Time Frame: for the follow-up period of 6 months
as assessed by a qualitative questionnaire (HIT-6)
for the follow-up period of 6 months
Occurrence of autonomic symptoms
Time Frame: for the follow-up period of 6 months
assessed on Cranial Autonomic Parasympathetic Symptoms (CAPS) scale
for the follow-up period of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Norwegian University of Science and Technology

Collaborators

St. Olavs Hospital

Investigators

  • Study Director: Lars Jacob Stovner, prof MD, Norwegian University of Science and Technology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 18, 2017

Primary Completion (ACTUAL)

September 13, 2019

Study Completion (ACTUAL)

September 13, 2019

Study Registration Dates

First Submitted

February 13, 2017

First Submitted That Met QC Criteria

February 23, 2017

First Posted (ACTUAL)

February 28, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 23, 2021

Last Update Submitted That Met QC Criteria

June 17, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OTOBLOCKCH2016
  • 2016-004213-28 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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