Cluster HeadachePhase 3BASICNCT03944876
Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache
A Phase 3 study testing Botulinum toxin type A in people with Cluster Headache, run by Norwegian University of Science and Technology at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Cluster Headache
- What is being tested?
- Botulinum toxin type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 1 Nov 2019to Sep 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
Erling Tronvik, md phd contact
5 sites in 5 countries
Germany1 site, 1 recruiting
- Recruiting
Praxisklinik Ulmenhof
Hamburg
Alexandre Thomas Assaf, dr
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta (CBNI)
Milan
Massimo Leone, md prof, +39 02.23941, Massimo.Leone@istituto-besta.it
Norway1 site, 1 recruiting
- Recruiting
St Olavs Hospital
Trondheim
Erling Tronvik, md phd, +47 40458528, erling.tronvik@ntnu.no
Spain1 site, 1 recruiting
- Recruiting
Department of Neurology, University Clinic Hospital. Catholic University of Valencia
Valencia
Miguel Lainez, md prof, +34 963868863, miguel.lainez@sen.es
United Kingdom1 site, 1 recruiting
- Recruiting
National Hospital of Neurology and Neurosurgery, University College of London
London
Manjit Matharu, MD phd, +44 7976264746, manjit.matharu@nhs.net
About this study
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 .
- Conditions
- Cluster Headache
- Being tested
- Botulinum toxin type A, placebo
- Keywords
- Botulinum Toxin Type A, Sphenopalatine Ganglion Block, Autonomic Nerve Block, Injections
- Medical subject headings
- Cluster Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called botox
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)
placeboDrug
Also called Sodium Chloride
0.5 ml Sodium Chloride (NaCl) 0.9% Braun. One injection in the headache side of the face, targeted at the sphenopalatine ganglion (SPG)
| Study group | Role | What they receive |
|---|---|---|
| Botox injections towards SPG | Experimental | Botulinum Toxin type A injections Receives: Drug: Botulinum toxin type A |
| Controls | Placebo comparator | placebo injections Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: week 5 through week 8 in the post-injection period
Secondary outcomes (7)
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
Measured: week 1 through week 12 in the post-injection period
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
Measured: week 9 through week 12 in the post-injection period
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
Measured: week 5 through week 8 in the post-injection period
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
Measured: week 9 through week 12 in the post-injection period
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
Measured: week 5 through week 8 in the post-injection period
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
Measured: week 5 through week 8 in the post-injection period
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.
Measured: week 5 through week 8 in the post-injection period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2019
- Study start1 Nov 2019
- Primary completionSep 2025 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cluster HeadacheStudies of the same condition, open and under way.
- More trials run by Norwegian University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Norwegian University of Science and Technology
- Sponsor type
- University, hospital or other
- Collaborators
- St. Olavs Hospital, University College, London, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Catholic University of Valencia, PRAXISKLINIK ULMENHOF
- Responsible party
- Sponsor
- Investigators
- Geir Bråthen, md phd, Study director, St. Olavs Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03944876
- Sponsor's protocol ID
- 2018/1821
- Other IDs
- 2018-003148-21, 2018
- Acronym
- BASIC
- Status last verified
- Nov 2024
- First submitted
- 26 Apr 2019
- Last updated
- 19 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication will be shared within 6 months after study results publication
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache
- ClinicalTrials.gov ID
- NCT03944876
- Acronym / sponsor ID
- BASIC / 2018/1821
- Conditions
- Cluster Headache
- Keywords
- Botulinum Toxin Type A, Sphenopalatine Ganglion Block, Autonomic Nerve Block, Injections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Norwegian University of Science and TechnologyUniversity, hospital or other
- Collaborators
- St. Olavs Hospital, University College, London, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Catholic University of Valencia, PRAXISKLINIK ULMENHOF
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 10 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botox injections towards SPG | Experimental | Drug: Botulinum toxin type ABotulinum Toxin type A injections |
| Controls | Placebo comparator | Drug: placeboplacebo injections |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (34 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum toxin type AAlso: botoxBotulinum 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) | Drug | Botox injections towards SPG |
| placeboAlso: Sodium Chloride0.5 ml Sodium Chloride (NaCl) 0.9% Braun. One injection in the headache side of the face, targeted at the sphenopalatine ganglion (SPG) | Drug | Controls |
Primary outcome
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
Time frame: week 5 through week 8 in the post-injection period
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.
7 secondary outcomes
Difference in occurrence of adverse events (AEs) and serious adverse events (SAEs) in the active group versus the placebo group
Time frame: week 1 through week 12 in the post-injection period
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
Time frame: week 9 through week 12 in the post-injection period
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
Time frame: week 5 through week 8 in the post-injection period
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
Time frame: week 9 through week 12 in the post-injection period
Difference in the number of therapeutic responders in the active group versus the placebo group.
Time frame: week 5 through week 8 in the post-injection period
Difference in the number of attack frequency responders
Time frame: week 5 through week 8 in the post-injection period
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.
Time frame: week 5 through week 8 in the post-injection period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2024.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication will be shared within 6 months after study results publication
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Yogabased Movements for Primary Headaches (Migraine and/or Cluster Headache) - YOURHEAD - a Pilot Study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Erling Tronvik, md phd contact
Geir Bråthen, md phd study director
St. Olavs Hospital
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Botulinum toxin type A in people with Cluster Headache, run by Norwegian University of Science and Technology at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany, Italy, Norway, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tore Wergeland Meisingset, md phd (+47 728 21 335, tore.w.meisingset@ntnu.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: week 5 through week 8 in the post-injection period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.