Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache

NCT03944876 | Recruiting Phase 3 DMC

• 2 other identifiers: 2018/18212018-003148-21
• Study Type: interventional
• Target: 112
• Locations: 5 countries
• Sites: 5

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 .

Conditions

Cluster Headache

Keywords

Botulinum Toxin Type A; Sphenopalatine Ganglion Block; Autonomic Nerve Block; Injections

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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

  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.

  week 5 through week 8 in the post-injection period

Study Arms (2)

Botox injections towards SPG

EXPERIMENTAL

Botulinum Toxin type A injections

Drug: Botulinum toxin type A

Controls

PLACEBO COMPARATOR

placebo injections

Drug: placebo

Interventions

Botulinum toxin type A DRUG

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)

Also known as: botox

Botox injections towards SPG

placebo DRUG

0.5 ml Sodium Chloride (NaCl) 0.9% Braun. One injection in the headache side of the face, targeted at the sphenopalatine ganglion (SPG)

Also known as: Sodium Chloride

Controls

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.).
• 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.

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator
• University College, London: collaborator
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: collaborator
• Catholic University of Valencia: collaborator
• PRAXISKLINIK ULMENHOF: collaborator

Study Sites (5)

Praxisklinik Ulmenhof

Hamburg, Germany

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta (CBNI)

Milan, Italy

RECRUITING

St Olavs Hospital

Trondheim, Norway

RECRUITING

Department of Neurology, University Clinic Hospital. Catholic University of Valencia

Valencia, Spain

RECRUITING

National Hospital of Neurology and Neurosurgery, University College of London

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Cluster Headache

Interventions

Botulinum Toxins, Type A; Sodium Chloride

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Geir Bråthen, md phd

  St. Olavs Hospital

  STUDY DIRECTOR

Central Study Contacts

Tore Wergeland Meisingset, md phd

CONTACT

+47 728 21 335; tore.w.meisingset@ntnu.no

Erling Tronvik, md phd

CONTACT

erling.tronvik@ntnu.no

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: May 10, 2019
• Study Start: November 1, 2019
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after study results publication
• Access Criteria: erling.tronvik@ntnu.no

Locations

IT (1); GB (1); ES (1); DE (1); NO (1)