"Follow the Sutures". A New Procedure for Injection of Botulinum Toxin for Chronic Migraine
Condition: Migraine Disorders; Chronic Disease
MeSH terms: Migraine Disorders; Chronic Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      The study is an an open-label, non-con trolled, single-arm and single-center phase II study,
      at the outpatient clinic of the Department of Neurology and Clinical neurophysiology at St.
      Olavs Hospital, Trondheim, Norway. The study was originally also planned at the Mayo Clinic,
      Scottsdale, AZ, USA, but because the study there had not been started before the COVID-19
      pandemic, the study was performed only in Trondheim. Potential study participants should be
      identified among the regular outpatients at the Department of Neurology at St. Olavs
      hospital. Potential participants should recceive an email with the informed consent form,
      which should be signed at the screening visit where a detailed medical history and medical
      examination should be per formed. Patients should complete a paper head ache diary, recording
      pain intensity and duration, concomitant migraine symptoms (nausea, vomiting, phono- and
      photophobia), acute medication (type, number of doses) and work absence (yes/no/not
      relevant). Also, they should record any adverse events. After 7-14 days, they should receive
      a telephone call from a nurse asking about adverse events and concom itant medication and
      reminding them to maintain the daily diary. After a baseline period of at least 28 days,
      diaries should be reviewed at a treatment visit, and each participant should receive
      injections according to the described procedure. Women of child bearing potential should have
      a negative pregnancy test before the injections. The duration of the injection procedure
      should be measure with a stopwatch and immediately after the injections, the patient should
      be asked to record on a VAS scale (0-10) the level of pain of the procedure and the
      investigator recorded the degree of bleeding (no, mild, moderate, marked) and any other
      injection-related adverse events (AEs). Patients should then be asked were asked to keep a
      headache diary for another 12 weeks or more, before the end of the study visit. During this
      period, they should receive a call from the study nurse at weeks 2 and 9, reminding to keep
      the headache diary, and asking about AEs and concomitant medication. They should be also
      asked whether they had noticed any change in their ability to make forehead wrinkles (no,
      little, moderate, marked, full paralysis)
    

Intervention name(s): BoNT-A
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): Botox; Botulinum Toxin Type A
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Botulinum Toxins, Type A; Injections; Cranial Sutures; Head