Follow the Sutures. A New Procedure for Injection of Botulinum Toxin for Chronic Migraine

Study Overview
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Brief Summary
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There is no doubt that chronic migraine is a large public health problem, which is both disabling and costly. Many patients and headache doctors see Botulinum toxin (Botox) treatment as a big stride forward, but it is a problem that the effect has been shown in only one study, with a low therapeutic gain. For this reason, before this costly treatment is expanded to potentially several thousand patients in Norway, it would be highly desirable that 1) there is additional good scientific evidence for use of Botox , 2) a more effective treatment procedure is developed, 3) the potential for unblinding is reduced, and 4) the dose, number of injection sites and cost can be halved, and 5) the adverse effects are minimized. These may be the results of this pilot project where injections are given along the sutures, which can open up for a later randomized, blinded and controlled study.

Official Title
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Follow the Sutures. An Open Multicenter, Multinational Pilot Study to Explore Tolerability, Safety and Effect of a New Procedure for Injecting Botulinum Toxin in the Head Against Chronic Migraine

Conditions
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Migraine Disorders, Chronic Disease

Intervention / Treatment
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* Drug: BoNT-A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic migraine, as defined in the ICHD-3 beta version Chronic migraine should have been present for at least ½ year prior to evaluation for study inclusion For women of child-bearing potential there must be no pregnancy or planned pregnancy during the study period, and use of highly effective contraception Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations Exclusion Criteria: Diseases that are contraindications for use of Botulinum toxin A (Myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, other diseases interfering with neuromuscular function) Allergy to Botulinum toxin A Other primary or secondary headache disorder, including medication overuse headache (MOH). This means that at least one attempt to withdraw acute medication should have been performed earlier, but without success Severe depression or other psychiatric disorder that may interfere with the treatment Abuse of alcohol or illicit drugs Use of more than one headache prophylactic medication, or change in type and dose of prophylactic medication < 28 days before start of baseline period Previous exposure at any time to any botulinum toxin serotype Infection at one or more injection site(s) Having received extracranial nerve block, cervical facet injection, or other interventional procedure for headache within the prior 3 months Use of opioids or barbiturate containing medication(s) > 10 days per month within the preceding 3 months Participating in another trial that might affect the current study Should not participate in the opinion of the investigator (e.g. not able to comply with study procedures).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BoNT-A injected<br>BoNT-A (Botulinum toxin A) injected in the head on specific sites and in half the usual concentration | Drug: BoNT-A<br>* 90U BoNT-A, given in one treatment as 18 injections of 5u (0.2 ml) each, on specific preselected sites along the sutures of the skull. First 100 U of Botox® is solved in 4 ml (cc) of isotone saline water (9 mg/ml), distributed in 4 syringes. This is half the usual concentration, allowing for better diffusion in order to reach the target structures.<br>* Other names: Botulinum Toxin Type A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of adverse events | adverse events (other than clearly related to migraine) will be recorded in the diary by the patients and reviewed during the scheduled visits | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| moderate-severe headache days 5-8 weeks after injection compared with baseline | course of headache is recorded in the headache diary before and after injection | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Botulinum Toxins, Type A, Injections, Cranial Sutures, Head