(chronic) migraine, migraine, medication-overuse headache
Conditions
Interventions
Participants will be randomized to receive either:
1. "Verum": Withdrawal therapy with one-time concommitant botulinum toxin A injections in 31 locations according to the injection protocol by Allerg
2. "Placebo": Withdrawal therapy with one-time concommitant low-dose botulinum toxin A injections in the facial region and NaCl injections in the other regions according to the injection protocol by A
Sponsors
Leiden university Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: Suffering from chronic migraine according to the ICHD-II criteria for chronic migraine with medication overuse according to the ICHD-II criteria.
Exclusion criteria
Exclusion criteria: 1. General exclusion criteria: A. Age under 18 years; B. Other neurological conditions that may in the opinion of the investigators may interfere with the trial. Any oncological or psychiatric disease, other than the specific types described in the inclusion criteria; C. Any cognitive disorders and/or behavioural problems which in the opinion of the clinician may interfere with the study; D. Current abuse of soft drugs or hard drugs or history of abuse of soft drugs or hard drugs in the past 12 months as defined in the DSM-IV criteria under 'Substance abuse' or 'Substance dependence'.(abuse of amphetamines, cocaine, heroin, cannabis); E. Use of non-triptan or non-analgesic acute anti-headache medication (e.g. ergots, opioids, barbiturates); F. Pregnancy, planned pregnancy, current nursing. Additionally, all participants will be required to use adequate contraceptive methods; G. Inability to complete the (electronic) diary in a sensible and accurate manner; H. Enrolment in other studies that in the opinion of the clinician may confound the results of this study. 2. Btx-specific exclusion criteria: A. Any motor neuron disorder; B. Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation; C. Infection at the proposed injection site(s); D. (Suspected) clotting disorder; either of pathological or iatrogenic origin (e.g. caused by marcoumar, sintrom). 3. MRI-specific exclusion criteria: A. Implanted pacemaker or implanted defibrillator-device; B. Surgical clips in cerebral vasculature; C. Metal debris in the eyes; D. Non-removable hearing-aid; E. Non-removable neurostimulator; F. Hydrocephalus-pump; G. Denture with magnetic fixation; H. Copper containing Intra-uterine Device; I. History of surgery in which metal implants were implanted; J. Weight over 160kg.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome measure is the relative reduction in headache days per month, in a comparison of the last month of withdrawal (month 3) with the baseline period (month -1). A headache day is defined as a day on which there is at least one period of ≥ 4 hours of continuous headache. The relative reduction will be measured in the Btx and placebo groups and will be adjusted using multivariate analysis for depression scores at baseline and support by the headache nurse. As an alternative primary outcome measure, we will measure quality of life during the withdrawal trial. This will be measured by the Sumscore on the SF-36 questionnaire at timepoint 0, 1, 2 and 3. Addendum: The primary outcome measure is the relative reduction in headache days per month, in a comparison of the last month of withdrawal (month 3) with the baseline period (month -1). A headache day is defined as a day on which there is migraine or non-migraine headache . The relative reduction will be measured in the Btx and placebo groups and will be adjusted using multivariate analysis for depression, anxiety, gender, age, headache days at baseline and support by the headache nurse. | — |
Secondary
| Measure | Time frame |
|---|---|
| The differences between Btx and placebo groups will be assessed by measuring absolute and relative reduction in migraine and headache days on time points 3, 6, 9 and 12, the number of patients achieving a 50% or more decrease from baseline (month -1) in the frequency of migraine days and migraine episodes at time points 3 and 12 and absolute and relative reductions of HIT-6, CES-D and HADS-D scores at time points 3, 6, 9 and 12 and changes in these scores during the withdrawal trial. Also subjective satisfaction with both treatment and treatment outcome will be assessed. The difference between maximal versus minimal support by a headache nurse, responders (≥50% reduction in headache days) versus non-responders and depressive (HADS≥8) versus non-depressive chronic migraineurs will be assessed by measuring the absolute and relative reduction in migraine and headache days on time points 3, 6, 9 and 12, the number of patients achieving a 50% or more decrease from baseline (month -1) in the frequency of migraine days and migraine episodes at both time points and absolute and relative reductions of HIT-6, SF-36 CES-D and HADS-D scores at time points 3, 6, 9 and 12. Headache relapse rates at t=12 will be assessed and compared between Btx and placebo-treatment, minimal or maximal support by the headache nurse and depressive versus non-depressive groups. The change in reactiveness of the trigeminal blink reflex during the course of the trial will be assessed. Blink reflex will be tested at time points 0, 3 and 12. Addendum: As a secondary outcome measure, we will measure quality of life during the withdrawal trial. This will be measured by the Sum scores on the SF-36 questionnaire at time point 3 compared to time point 0. The SF 36 questionnaire will be assessed at time points 6, 9 and 12 as well. Furthermore, he differences between Btx and placebo groups will be assessed by measuring absolute and relative reduction in migraine and headache days and the tot | — |
Contacts
Public ContactD.A. Kies
P.O.box 9600
Outcome results
None listed