Cadasil, Migraine
Conditions
Brief summary
Researchers are trying to find out more about the side effects of fremanezumab when treating patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) for migraine headaches.
Detailed description
Subjects will receive 4 to 20 weeks of placebo injections followed by 12 weeks of monthly administered fremanezumab by subcutaneous injection (225 mg split four weeks apart for 12 weeks). Following completion of the 12 weeks of therapy, the participant will return to placebo for the washout period. Both the patient and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.
Interventions
DRUGFremanezumab
Subjects will receive a single dose total 225 mg (1 injection of 225 mg per 1.5 mL injection) followed by a single dose of 225 mg (1 1.5mL injection) at four week intervals. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.
DRUGPlacebo
Placebo injections during the run in and washout serves as the control condition. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 70 years old * English speaking * Diagnosis of CADASIL confirmed by presence of a pathogenic NOTCH3 gene mutation * Diagnosis of migraine for at least 12 months and diagnosis of chronic migraine for at least 28 days according to the International Classification of Headache Disorders * MIDAS score of \>10 points * Ability to provide written informed consent
Exclusion criteria
* History of ischemic stroke within 4 weeks of screening assessment * Screening blood pressure \>150 mm Hg * Use of onabotulinum toxin A 4 months prior to trial or other injectable/stimulatory/magnetic method of headache control * Use of opiates or barbiturates 4 days prior to trial * Patients with competing intracerebral pathology (e.g. history of intracerebral hemorrhage, multiple sclerosis) * NYHA Class III or IV congestive heart failure * History of myocardial infarction * History of coronary bypass surgery or coronary stenting * Pregnancy or breastfeeding * Contraindication to undergoing brain MRI per standard clinical practice guidelines * Vulnerable populations, including incarcerated inmates, dementia, and inability to provide consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in migraine-related disability | Baseline, 2 week intervals up to 48 weeks | Measured using the The Migraine Disability Assessment (MIDAS) questionnaire which is a brief, self-administered questionnaire designed to quantify headache-related disability over a 3 month period using number of days |
| Change in headache intensity | Baseline, 2 week intervals up to 48 weeks | Measured using Headache Impact Test (HIT)-6 scores with the answers being never, rarely, sometimes, very often or always and equating to 6, 8, 10, 11, and 13 points respectively. Each answer is summated to equal the final score. |
| Adverse events | 48 weeks | Number of adverse events reported |
Outcome results
None listed