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Migraine DisordersPhase 3MiBlockNCT04069897

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

A Phase 3 study testing Botulinum toxin type A in people with Migraine Disorders, run by St. Olavs Hospital at 4 sites in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Migraine Disorders
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
170 participants
Where
4 sitesNorway
Study dates
1 Oct 2019to 13 Jun 2026
Phase
Phase 3
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participants must meet all of the inclusion criteria to participate in this study:
  • 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
  • Migraine, with or without aura, fulfilling the International Classification of Headache Disorders (ICHD) III criteria 1.3. for chronic migraine at time of inclusion
  • Chronic migraine at least for a period of 1 year prior to inclusion
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  • 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)
  • Ability to understand study procedures and to comply with them for the entire length of the study

Who cannot join

  • All candidates meeting any of the exclusion criteria at baseline or visit 2 will be excluded from study participation:
  • 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
Show all 42Show fewer
  • 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
  • Botulinum toxin injections in the head and neck region, as part of migraine treatment or otherwise indicated on medical or cosmetic grounds, in the last 4 months before inclusion.
  • The discontinuation of CGRP-antagonists within 3 months before study inclusion or 5 half-lives, whichever is longer,
  • Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study inclusion 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.
  • 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.
  • Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the SPG.
  • Subject has had blocks of short-acting anaesthetics of the SPG in the last 3 months.
  • Subject is or has been treated with occipital nerve stimulation or deep brain stimulation.
  • Ongoing abuse of drugs (including narcotics) or alcohol.
  • More than 4 days of opioid use per month (including codeine and tramadol), and any use of barbiturates
  • Treatment with pharmacological substances prior to SPG-injection that may interact with BTA (aminoglycosides, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), and anticholinesterases).
  • Inadequate contraceptive use. Women of childbearing potential (WOCBP) who do not use highly effective contraception (HEC) or use other medication that may interact and/or otherwise reduce the efficacy of the contraceptive agents in use.
  • Subject has undergone facial surgery in the area of the pterygopalatine fossa or zygomaticomaxillary at 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.
  • 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 with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator
  • 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 disorders that severely inhibits lacrimation, at the discretion of the investigator
  • Patients with previous ischemic cardiovascular and cerebrovascular disorder with, in the opinion of the investigator, a moderate to high risk of new ischemic episodes.
  • Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
  • Subject has a history of bleeding disorders or coagulopathy, that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
  • Unable to stop antithrombotic medication e.g. platelet aggregation inhibitors and/or anticoagulation therapy, prior to procedure.
  • 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
  • has any other condition, which, in the opinion of the investigator, makes the patient inappropriate for inclusion in the study
  • 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

4 sites in 1 country.

Norway4 sites

  • Haukeland University Hospital, department of Neurology

    Bergen

  • Nordland Hospital, department of Neurology

    Bodø

  • Nevroklinikken Universitetet i Oslo, Oslo Universitetssykehus HF

    Oslo

  • St Olavs Hospital, Trondheim University Hospital

    Trondheim

Other trials in Norway

About this study

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.

Being tested
Botulinum toxin type A, placebo
Keywords
Botulinum Toxin Type A, Sphenopalatine Ganglion Block, Autonomic Nerve Block, Injections
Medical subject headings
Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Botulinum toxin type ADrug

    Also called botox, Allergan

    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.

  • placeboDrug

    Also called sodium chloride

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

Study groups in NCT04069897
Study groupRoleWhat they receive
Botox injections towards SPGExperimentalBotulinum Toxin type A injections
Receives: Drug: Botulinum toxin type A
ControlsPlacebo comparatorPlacebo injections
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: week 5 through week 8 in the post-injection period

Secondary outcomes (8)

  1. Occurrence of adverse events and serious adverse events in the treatment

    All adverse events and serious adverse events occurring in the 3 months follow up are registered in an electronic 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

  2. Change from baseline in the mean monthly migraine days in the treatment

    A migraine day is defined as one day with headache pain fulfilling the ICHD3-criteria for migraine or probable migraine. However, a headache duration of less than 4 hours is allowed if the subject takes and responds to triptans. The frequency of headache days in the baseline period are compared to the frequency in week 5-8 post-intervention

    Measured: week 5 through week 8 in the post-injection period

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

    A 30% treatment response is defined as a patient with a ≥ 30% reduction in frequency of headache days during weeks 5 - 8 post-intervention compared to baseline. Headache is defined as in the primary outcome, i.e. moderate to severe headache days. The number of responders is compared between the intervention and the placebo group

    Measured: week 5 through week 8 in the post-injection period

  4. Change from baseline in the mean monthly headache intensity in the treatment

    Attack intensity is reported daily on a 11-point numerical response scale (NRS) in the electronic headache diary. The mean attack intensity in week 5 - 8 post-intervention is compared to baseline in the active group versus the placebo group.

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

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

    The difference in hours with NRS ≥4 in the baseline period and weeks 1-4, 5-8 and 9-12 post injection are compared between the active group and the placebo group

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

  6. Change from baseline in the mean monthly number of days with rescue medication in the treatment

    Any use of rescue medication is reported in the headache diary every day. The number of days with registered use of any headache related rescue medication in weeks 1-4, 5-8 and 9-12 post-intervention is compared to the baseline period

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

  7. Migraine specific quality of life questionnaire

    Study participants will fill in the 6-question Headache impact test (HIT-6) at visit 1 (at inclusion) and at week 8 and week 12 postintervention. Scores are compared between the placebo and the treatment group

    Measured: week 8 and week 12 post-injection

  8. Migraine specific quality of life questionnaire

    Study participants will fill in the 14-question Migraine-Specific Quality-of-Life Questionnaire Version 2.1 (MSQ) at visit 1 (at inclusion) and at week 8 and week 12 postintervention. Scores are compared between the placebo and the treatment group

    Measured: week 8 and week 12 post-injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2019
  2. Study start1 Oct 2019
  3. Primary completion13 Jun 2025
  4. Study completion13 Jun 2026

Resources

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
170 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04069897
Sponsor's protocol ID
2018/2161
Other IDs
2018-004053-24, 2018
Acronym
MiBlock
Status last verified
Aug 2026
First submitted
22 Aug 2019
Last updated
11 Aug 2026
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

Publications

  • Wergeland T, Simpson M, Aschehoug I, Oie L, Hara S, Skalstad ETV, Salvesen O, Tronvik E, Bratbak D. OnabotulinumtoxinA blockade of the sphenopalatine ganglion in treatment-resistant chronic migraine (MiBlock): rationale, design and study protocol for a multi-centre, investigator initiated, randomised, quadruple-blinded placebo-controlled trial. F1000Res. 2026 Feb 5;14:564. doi: 10.12688/f1000research.164241.2. eCollection 2025.

    PubMed 41727558

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Botulinum toxin type A in people with Migraine Disorders, run by St. Olavs Hospital at 4 sites in Norway.

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 19 inclusion and 42 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: finished, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Norway. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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

On the ClinicalTrials.gov record for NCT04069897, which also lists 1 linked publication.

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 11 Aug 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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