Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache (BASIC)
Primary Purpose
Cluster Headache
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Botulinum toxin type A
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cluster Headache focused on measuring Botulinum Toxin Type A, Sphenopalatine Ganglion Block, Autonomic Nerve Block, Injections
Eligibility Criteria
Inclusion Criteria:
- Informed and written consent.
- Male or female, 18-85 years of age
- Headache attacks fulfilling the International Classification of Headache Disorders (ICHD) III criteria for chronic cluster headache (CCH) 3.1.2.
- Dominant headache laterality with ≥ 80% of cluster headache attacks on one side.
- Subject reports ≥ 8 cluster attacks/week on the side of their dominant headache laterality in the 3 months prior to inclusion and in the baseline period.
- The condition is pharmacologically refractory defined as suboptimal effect or intolerable side effects or contraindication for verapamil or lithium or suboccipital steroid injection.
- Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
- Subject is able to differentiate concomitant headaches from cluster headache.
- In case of women of childbearing potential (WOCBP) they have to be using highly effective contraception in a period of 4 weeks after injection.
- Ability to understand study procedures and to comply with them for the entire length of the study
Exclusion Criteria:
- Subject has had a change in type, dosage or dose frequency of preventive headache medications < 1 months prior to baseline/screening or 5 half-lives, whichever is longer.1
- Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration.
- Non-responder to both oxygen and triptan.
Non-responder in regular clinical practice at the discretion of the investigator to ≥4 of the listed preventive medications
- Verapamil
- Lithium
- Topiramate
- Valproate
- Greater occipital nerve (GON) block
- CGRP-antagonist
- 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.
- 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.
- Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
- Abuse of drugs or alcohol.
- Use of opioids for ≥10 days per month.
- Treatment with pharmacological substances that may interact with BTA (aminoglycosides, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), lincosamides, polymyxins, quinidine, magnesium sulfate or anticholinesterases.).
- WOCBP that do not adhere to the requirements for HEC, as noted in inclusion criteria 9 and outlined in section 3.3.
- Pregnancy or breastfeeding in the study period
- 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.
- Facial anomaly or trauma which renders the procedure difficult.2
- Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
- 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.
- 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.
- Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator.
- 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.
- Patient with disorders that are known contraindication for Botox® treatment, especially neuromuscular disorders such as motorneuron disorders and myasthenic syndromes
- 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.
- 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.
- Subject is currently or has been previously treated with occipital nerve stimulation or deep brain stimulation.
- Subject has had blocks of short-acting anaesthetics of the ipsilateral SPG in the last 3 months.
- Subject has undergone onabotulinumtoxinA injections of the head and/or neck or has had an occipital nerve block in the last 3 months.
- Subject is anticipated to require any excluded medication, device, or procedure during the study.
- Subject has a history of bleeding disorders and in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
- Subject has a history of coagulopathy.
- Subject is unable to stop antithrombotic medication, eg. anticoagulants and/or antiplatelet therapy, before procedure.
- The subject has been diagnosed with another trigeminal autonomic cephalalgia or trigeminal neuralgia.
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.
- The patient is a study centre employee who is directly involved in the study or the relative of such an employee.
Sites / Locations
- Universitätsklinikum Hamburg Eppendorf
- Fondazione IRCCS Istituto Neurologico Carlo Besta (CBNI)Recruiting
- St Olavs HospitalRecruiting
- Department of Neurology, University Clinic Hospital. Catholic University of ValenciaRecruiting
- National Hospital of Neurology and Neurosurgery, University College of LondonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Botox injections towards SPG
Controls
Arm Description
Botulinum Toxin type A injections
placebo injections
Outcomes
Primary Outcome Measures
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week at weeks 5-8 post-intervention in the treatment group versus the placebo group
Change from baseline to weeks 5-8 post-intervention in number of cluster headache attacks per week in the active group versus the placebo group. The number of cluster headache attacks is collected in a headache diary.
Secondary Outcome Measures
Difference in occurrence of adverse events (AEs) and serious adverse events (SAEs) in the active group versus the placebo group
All adverse events and serious adverse events occurring in the 3 months follow up are registered in an electronic case report form (CRF). Frequency of AE and SAE are compared between the placebo group and the treatment group
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week during weeks 9-12 post-intervention in the active group versus the placebo group
Change from baseline to weeks 9-12 post-intervention in number of cluster headache attacks per week in the active group versus the placebo group. The number of cluster headache attacks is collected in a headache diary
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week at weeks 5-8 post-intervention in the active group versus the placebo group, in the prespecified subgroups
Change from baseline to weeks 5 - 8 post-intervention in number of cluster headache attacks per week comparing high versus low attack frequency and low versus high attack frequency variation in the entire baseline period. Comparisons are done between the active and the placebo group. The number of cluster headache attacks is collected in a headache diary
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week during weeks 9-12 post-intervention in the active group versus the placebo group, in the prespecified subgroups
Change from baseline to weeks 9-12 post-intervention in number of cluster headache attacks per week comparing high versus low attack frequency and high versus low attack frequency variation in the entire baseline period. Comparisons are done between the active and the placebo group. The number of cluster headache attacks is collected in a headache diary
Difference in the number of therapeutic responders in the active group versus the placebo group.
Number of therapeutic responders as defined as a ≥ 30% reduction in attack frequency, intensity or both during weeks 5 - 8 post-intervention compared to baseline week 5-8. The number in the placebo and intervention group are compared
Difference in the number of attack frequency responders
Number of attack frequency responders as defined as a ≥ 30% reduction in attack frequency during weeks 5-8 post-intervention compared to baseline. The number in the placebo and intervention group are compared
Difference in change from baseline week 5-8 in mean attack intensity week 5 - 8 post-intervention in the active group versus the placebo group.
Mean attack intensity (10-point numerical response scale - NRS) week 5-8 post intervention compared to baseline in the intervention group versus the placebo group.
Full Information
NCT ID
NCT03944876
First Posted
April 26, 2019
Last Updated
September 28, 2023
Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital, University College, London, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Catholic University of Valencia, Universitätsklinikum Hamburg-Eppendorf
1. Study Identification
Unique Protocol Identification Number
NCT03944876
Brief Title
Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache
Acronym
BASIC
Official Title
Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2019 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital, University College, London, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Catholic University of Valencia, Universitätsklinikum Hamburg-Eppendorf
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Cluster headache is a primary headache condition characterized by clusters of one-sided, high-intensity pain attacks. The headache may be episodic or chronic. Treatment options are limited and their effects unsatisfactory. An important nerve pathway involved in the pain attacks has a switching station at the sphenopalatine ganglion (SPG) located in the depth of the facial bones. SPG is a known therapy target for cluster headache. The area can be identified on CT images, but is difficult to access due to its location. Thus, the Multiguide navigation system has been developed to enable precise delivery of the drugs that target SPG activity. In Trondheim, two phase 1 / Phase 2 study have been carried out using botulinum toxin A (Botox®) against SPG in patient with chronic cluster headache and chronic migraine. The results indicate that such a treatment strategy is safe and beneficial. The current study is a randomized, placebo-controlled, triple-blinded study to investigate whether precise single-injection of botulinum toxin A reduces the frequency of attacks in chronic cluster headache .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cluster Headache
Keywords
Botulinum Toxin Type A, Sphenopalatine Ganglion Block, Autonomic Nerve Block, Injections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Botox injections towards SPG
Arm Type
Experimental
Arm Description
Botulinum Toxin type A injections
Arm Title
Controls
Arm Type
Placebo Comparator
Arm Description
placebo injections
Intervention Type
Drug
Intervention Name(s)
Botulinum toxin type A
Other Intervention Name(s)
botox
Intervention Description
Botulinum toxin 25 Allergan units in 0.5 ml Sodium Chloride (NaCl) 0.9 % Braun. One injection in the headache side of the face, targeted at the sphenopalatine ganglion (SPG)
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
Sodium Chloride
Intervention Description
0.5 ml Sodium Chloride (NaCl) 0.9% Braun. One injection in the headache side of the face, targeted at the sphenopalatine ganglion (SPG)
Primary Outcome Measure Information:
Title
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week at weeks 5-8 post-intervention in the treatment group versus the placebo group
Description
Change from baseline to weeks 5-8 post-intervention in number of cluster headache attacks per week in the active group versus the placebo group. The number of cluster headache attacks is collected in a headache diary.
Time Frame
week 5 through week 8 in the post-injection period
Secondary Outcome Measure Information:
Title
Difference in occurrence of adverse events (AEs) and serious adverse events (SAEs) in the active group versus the placebo group
Description
All adverse events and serious adverse events occurring in the 3 months follow up are registered in an electronic case report form (CRF). Frequency of AE and SAE are compared between the placebo group and the treatment group
Time Frame
week 1 through week 12 in the post-injection period
Title
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week during weeks 9-12 post-intervention in the active group versus the placebo group
Description
Change from baseline to weeks 9-12 post-intervention in number of cluster headache attacks per week in the active group versus the placebo group. The number of cluster headache attacks is collected in a headache diary
Time Frame
week 9 through week 12 in the post-injection period
Title
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week at weeks 5-8 post-intervention in the active group versus the placebo group, in the prespecified subgroups
Description
Change from baseline to weeks 5 - 8 post-intervention in number of cluster headache attacks per week comparing high versus low attack frequency and low versus high attack frequency variation in the entire baseline period. Comparisons are done between the active and the placebo group. The number of cluster headache attacks is collected in a headache diary
Time Frame
week 5 through week 8 in the post-injection period
Title
Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week during weeks 9-12 post-intervention in the active group versus the placebo group, in the prespecified subgroups
Description
Change from baseline to weeks 9-12 post-intervention in number of cluster headache attacks per week comparing high versus low attack frequency and high versus low attack frequency variation in the entire baseline period. Comparisons are done between the active and the placebo group. The number of cluster headache attacks is collected in a headache diary
Time Frame
week 9 through week 12 in the post-injection period
Title
Difference in the number of therapeutic responders in the active group versus the placebo group.
Description
Number of therapeutic responders as defined as a ≥ 30% reduction in attack frequency, intensity or both during weeks 5 - 8 post-intervention compared to baseline week 5-8. The number in the placebo and intervention group are compared
Time Frame
week 5 through week 8 in the post-injection period
Title
Difference in the number of attack frequency responders
Description
Number of attack frequency responders as defined as a ≥ 30% reduction in attack frequency during weeks 5-8 post-intervention compared to baseline. The number in the placebo and intervention group are compared
Time Frame
week 5 through week 8 in the post-injection period
Title
Difference in change from baseline week 5-8 in mean attack intensity week 5 - 8 post-intervention in the active group versus the placebo group.
Description
Mean attack intensity (10-point numerical response scale - NRS) week 5-8 post intervention compared to baseline in the intervention group versus the placebo group.
Time Frame
week 5 through week 8 in the post-injection period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Informed and written consent.
Male or female, 18-85 years of age
Headache attacks fulfilling the International Classification of Headache Disorders (ICHD) III criteria for chronic cluster headache (CCH) 3.1.2.
Dominant headache laterality with ≥ 80% of cluster headache attacks on one side.
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.
The condition is pharmacologically refractory defined as suboptimal effect or intolerable side effects or contraindication for verapamil or lithium or suboccipital steroid injection.
Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
Subject is able to differentiate concomitant headaches from cluster headache.
In case of women of childbearing potential (WOCBP) they have to be using highly effective contraception in a period of 4 weeks after injection.
Ability to understand study procedures and to comply with them for the entire length of the study
Exclusion Criteria:
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.
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.
Current or previous treatment with implanted medical devices targeting the SPG
Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration.
Non-responder to both oxygen and triptan.
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.
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.
Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
Abuse of drugs or alcohol.
Use of opioids for ≥10 days per month.
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.).
WOCBP that do not adhere to the requirements for HEC, as noted in inclusion criteria 9 and outlined in section 3.3.
Pregnancy or breastfeeding in the study period
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.
Facial anomaly or trauma which renders the procedure difficult.2
Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
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.
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.
Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator.
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.
Patient with disorders that are known contraindication for Botox® treatment, especially neuromuscular disorders such as motorneuron disorders and myasthenic syndromes
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.
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.
Subject has had blocks of short-acting anaesthetics of the ipsilateral SPG in the last 3 months.
Subject has undergone onabotulinumtoxinA injections of the head and/or neck in the last 3 months.
Subject is anticipated to require any excluded medication, device, or procedure during the study.
Subject has a history of bleeding disorders and in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
Subject has a history of coagulopathy.
Subject is unable to stop antithrombotic medication, eg. anticoagulants and/or antiplatelet therapy, before procedure.
The subject has been diagnosed with another trigeminal autonomic cephalalgia or trigeminal neuralgia.
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.
The patient is a study centre employee who is directly involved in the study or the relative of such an employee.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tore Wergeland Meisingset, md phd
Phone
+47 728 21 335
Email
tore.w.meisingset@ntnu.no
First Name & Middle Initial & Last Name or Official Title & Degree
Erling Tronvik, md phd
Email
erling.tronvik@ntnu.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geir Bråthen, md phd
Organizational Affiliation
St. Olavs Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsklinikum Hamburg Eppendorf
City
Hamburg
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandre Thomas Assaf, dr
Facility Name
Fondazione IRCCS Istituto Neurologico Carlo Besta (CBNI)
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Leone, md prof
Phone
+39 02.23941
Email
Massimo.Leone@istituto-besta.it
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erling Tronvik, md phd
Phone
+47 40458528
Email
erling.tronvik@ntnu.no
Facility Name
Department of Neurology, University Clinic Hospital. Catholic University of Valencia
City
Valencia
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miguel Lainez, md prof
Phone
+34 963868863
Email
miguel.lainez@sen.es
Facility Name
National Hospital of Neurology and Neurosurgery, University College of London
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manjit Matharu, MD phd
Phone
+44 7976264746
Email
manjit.matharu@nhs.net
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
all IPD that underlie results in a publication will be shared within 6 months after study results publication
IPD Sharing Time Frame
6 months after study results publication
IPD Sharing Access Criteria
erling.tronvik@ntnu.no
Learn more about this trial
Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache
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