Migraine Disorders
Conditions
Keywords
Botulinum Toxin Type A, Sphenopalatine Ganglion Block, Autonomic Nerve Block, Injections
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.
Interventions
DRUGBotulinum toxin type A
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.
DRUGplacebo
0.5 ml Sodium Chloride (NaCl) 0.9% Braun. Two injections, one in each side of the face, and targeting the sphenopalatine ganglion.
Sponsors
St. Olavs Hospital
Norwegian University of Science and Technology
Oslo University Hospital
Haukeland University Hospital
Nordlandssykehuset HF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
The participants must meet all of the inclusion criteria to participate in this study: 1. Informed and written consent. 2. Male or female, between 18 and 70 years of age 3. Masters a Scandinavian language at level sufficient to fully understand the written and verbal study information 4. Migraine, with or without aura, fulfilling the International Classification of Headache Disorders (ICHD) III criteria 1.3. for chronic migraine at time of inclusion 5. Chronic migraine at least for a period of 1 year prior to inclusion 6. Debut of episodic migraine before the age of 50, and chronic migraine before the age of 65. 7. 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 1. Beta-blockers 2. RA(A)S-inhibitors 3. Calcium-antagonists 4. Antiepileptic drugs 5. Tricyclic antidepressants 6. Botulinum toxin A 7. CGRP antagonists 8. 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. 9. Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period. 10. 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) 11. Ability to understand study procedures and to comply with them for the entire length of the study
Exclusion criteria
All candidates meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the mean monthly headache days at weeks 5 - 8 post intervention | week 5 through week 8 in the post-injection period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the mean monthly migraine days in the treatment | week 5 through week 8 in the post-injection period | 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 |
| number of treatment responders (≥ 30% reduction in mean monthly headache days) | week 5 through week 8 in the post-injection period | 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 |
| 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 | 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. |
| Occurrence of adverse events and serious adverse events in the treatment | week 1 through week 12 in the post-injection period | 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 |
| Change from baseline in the mean monthly number of days with rescue medication in the treatment | : week 1 through week 4, week 5 through week 8 and week 9 through week 12 in the post-injection period | 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 |
| Migraine specific quality of life questionnaire | week 8 and week 12 post-injection | 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 |
| 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 | 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 |
Countries
Norway
Contacts
STUDY_DIRECTORGeir Bråthen, md phd
St. Olavs Hospital
Outcome results
None listed