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

NCT04069897 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: 2018/21612018-004053-24
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 4

Brief Summary

This is a clinical trial to assess the efficacy of botox treatment of the sphenopalatine ganglion as an add-on treatment in drug resistant migraine. An injection targeting the ganglion is made possible by an image-guided device developed specifically for this purpose (MultiGuide) Study participants will be randomized to either placebo or botox after a 4 week run-in period. First, one injection will be given towards both the right and the left ganglion. After that there will be a follow-up of 12 weeks for efficacy and safety evaluation. The main efficacy measure is change in number of moderate to severe headache days before and after injection.

Conditions

Migraine Disorders

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the mean monthly headache days at weeks 5 - 8 post intervention

  Change from baseline to week 5-8 post-intervention in frequency of moderate to severe headache days. Headache episodes that qualify is in the study defined as headache pain duration of ≥4 hours with a peak severity of moderate or severe intensity, or of any severity or duration if the subject takes and responds to rescue medication.

  week 5 through week 8 in the post-injection period

Secondary Outcomes (8)

• Occurrence of adverse events and serious adverse events in the treatment

  week 1 through week 12 in the post-injection period

• Change from baseline in the mean monthly migraine days in the treatment

  week 5 through week 8 in the post-injection period

• number of treatment responders (≥ 30% reduction in mean monthly headache days)

  week 5 through week 8 in the post-injection period

• Change from baseline in the mean monthly headache intensity in the treatment

  week 1 through week 4, week 5 through week 8 and week 9 through week 12 in the post-injection period

• Change from baseline in the mean monthly occurrence of cumulative hours per 28 days of moderate/severe pain in the treatment

  : week 1 through week 4, week 5 through week 8 and week 9 through week 12 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. Two injections, one in each side of the face, and targeting the sphenopalatine ganglion.

Also known as: botox, Allergan

Botox injections towards SPG

placebo DRUG

0.5 ml Sodium Chloride (NaCl) 0.9% Braun. Two injections, one in each side of the face, and targeting the sphenopalatine ganglion.

Also known as: sodium chloride

Controls

Eligibility Criteria

• Age: 18 Years - 70 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, between 18 and 70 years of age
• Masters a Scandinavian language at level sufficient to fully understand the written and verbal study information
• Debut of episodic migraine before the age of 50, and chronic migraine before the age of 65.
• The condition is pharmacologically refractory as defined in this study as insufficient treatment effect, contraindication(s) or intolerable side effect(s) of at least 3 medications from at least 2 of the following medication (drug) classes
• Beta-blockers
• RA(A)S-inhibitors
• Calcium-antagonists
• Antiepileptic drugs
• Tricyclic antidepressants
• Botulinum toxin A
• CGRP antagonists
• Subject has had no change in type, dosage or dose frequency of preventive headache medications \< 3 months prior to baseline/screening, or a minimum of 5 half-lives, whichever is longer.
• Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
• In the case of women of childbearing potential (WOCBP) they have to commit to highly effective contraception in a period of 4 weeks after injection (for details, confer section 4.3)

You may not qualify if:

• Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
• Subject is unable to differentiate migraine from other concomitant headaches.
• Subject with secondary headache conditions, with the exception of medication overuse headache.
• Non-responder in regular clinical practice to preventive medications from ≥6 of the following 7 drug classes:
• Beta-blockers
• RA(A)S-inhibitors
• Calcium-antagonists
• Antiepileptic drugs
• Tricyclic antidepressants
• Botulinum toxin A
• CGRP antagonists
• Subject has had a change in type, dosage or dose frequency of preventive headache medications \< 3 months prior to baseline/screening, or a minimum of 5 half-lives, whichever is longer.
• Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration
• 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.
• Subject has had previous radiofrequency ablation, balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the trigeminal ganglion or any branch of the trigeminal nerve.

Sponsors & Collaborators

• St. Olavs Hospital: lead
• Norwegian University of Science and Technology: collaborator
• Oslo University Hospital: collaborator
• Haukeland University Hospital: collaborator
• Nordlandssykehuset HF: collaborator

Study Sites (4)

Haukeland University Hospital, department of Neurology

Bergen, Norway

Location

Nordland Hospital, department of Neurology

Bodø, Norway

Location

Nevroklinikken Universitetet i Oslo, Oslo Universitetssykehus HF

Oslo, Norway

Location

St Olavs Hospital, Trondheim University Hospital

Trondheim, Norway

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

Botulinum Toxins, Type A; Idoxuridine; Sodium Chloride

Condition Hierarchy (Ancestors)

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; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Geir Bråthen, md phd

  St. Olavs Hospital

  STUDY DIRECTOR

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: August 22, 2019
• First Posted: August 28, 2019
• Study Start: October 1, 2019
• Primary Completion: June 13, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

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

Locations

NO (4)