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

Primary Purpose

Cluster Headache

Status
Completed
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Botulinum Toxin Type A 25 IU
Botulinum Toxin Type A 12.5 IU
Sponsored by
Norwegian University of Science and Technology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cluster Headache focused on measuring Nerve block, Ganglia, Parasympathetic, Botulinum Toxins, Type A, Injection

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Neuroscience, Norwegian University of Science and Technology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Botulinum Toxin 25 IU

Botulinum Toxin 12.5 IU

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Number of adverse events (AE)
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.

Secondary Outcome Measures

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

Full Information

First Posted
February 13, 2017
Last Updated
June 17, 2021
Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03066635
Brief Title
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

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
April 18, 2017 (Actual)
Primary Completion Date
September 13, 2019 (Actual)
Study Completion Date
September 13, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cluster Headache
Keywords
Nerve block, Ganglia, Parasympathetic, Botulinum Toxins, Type A, Injection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Botulinum Toxin 25 IU
Arm Type
Experimental
Arm Description
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)
Arm Title
Botulinum Toxin 12.5 IU
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Botulinum Toxin Type A 25 IU
Other Intervention Name(s)
Botox, BTA, Allergan
Intervention Description
injection with 25 IU botulinum toxin towards the otic ganglion (symptomatic side) using image-guided navigation and the MultiGuide device
Intervention Type
Drug
Intervention Name(s)
Botulinum Toxin Type A 12.5 IU
Other Intervention Name(s)
Botox, BTA, Allergan
Intervention Description
injection with 12.5 IU botulinum toxin towards the otic ganglion (symptomatic side) using image-guided navigation and the MultiGuide device
Primary Outcome Measure Information:
Title
Number of adverse events (AE)
Description
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.
Time Frame
for the follow-up period of 6 months
Secondary Outcome Measure Information:
Title
Number of cluster headache attacks per week
Description
Number of cluster headache attacks per week
Time Frame
for the follow-up period of 6 months
Title
Duration of cluster headache attacks
Description
Duration of cluster headache attacks
Time Frame
for the follow-up period of 6 months
Title
Days without cluster headache attacks
Description
number of days without cluster headache attacks
Time Frame
for the follow-up period of 6 months
Title
Headache intensity on a 0-5 scale
Description
The headache intensity is registered in the headache diary using a scale from 0-5
Time Frame
for the follow-up period of 6 months
Title
Mean intensity per attack
Description
The headache intensity is registered in the headache diary using a scale from 0-5
Time Frame
for the follow-up period of 6 months
Title
Mean number of attacks with intensity grade 4-5
Description
Mean number of attacks with intensity grade 4-5
Time Frame
for the follow-up period of 6 months
Title
Functional level
Description
The functional level will be assessed by the WHO Performance Status
Time Frame
for the follow-up period of 6 months
Title
Triptan use per 4 weeks
Description
Triptan use per 4 weeks during the whole duration of the study
Time Frame
for the follow-up period of 6 months
Title
Number of analgesic doses per 4 weeks
Description
the number of analgesic doses per 4 weeks during the whole duration of the study
Time Frame
for the follow-up period of 6 months
Title
Absenteeism due to cluster headache
Description
Absenteeism due to cluster headache as assessed by the headache diary
Time Frame
for the follow-up period of 6 months
Title
disability
Description
as assessed by a qualitative questionnaire (HIT-6)
Time Frame
for the follow-up period of 6 months
Title
Occurrence of autonomic symptoms
Description
assessed on Cranial Autonomic Parasympathetic Symptoms (CAPS) scale
Time Frame
for the follow-up period of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars Jacob Stovner, prof MD
Organizational Affiliation
Norwegian University of Science and Technology
Official's Role
Study Director
Facility Information:
Facility Name
Department of Neuroscience, Norwegian University of Science and Technology
City
Trondheim
Country
Norway

12. IPD Sharing Statement

Citations:
PubMed Identifier
32583902
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.
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Botulinum Toxin Type A Block of the Otic Ganglion in Chronic Cluster Headache: Safety Issues

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