Role of Brivaracetam use for Treatment of Episodic Migraine (ROBUST-EM)
- Conditions
- Migraine without aura,
- Registration Number
- CTRI/2023/04/051915
- Lead Sponsor
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi 110002
- Brief Summary
Levetiracetam(LEV), an antiseizure medication with a good safety profile appears to be effective in treating migraine with and without aura. Brivaracetam (BRV), a congener of LEV is also used as an anti seizure medication, displays a higher affinity to its binding site synaptic vesicle protein 2A (SV2A), has higher potency and efficacy, favourable pharmacokinetic profile with lesser prevalence of adverse effects when compared with LEV. Therefore, BRV is potentially a good candidate drug for investigating its efficacy and safety for migraine prevention.
We therefore aim to conduct a double-blind, placebo-controlled study for its role in episodic migraine prevention.
All patients fulfilling inclusion and exclusion criteria will be evaluated as per a detailed structured proforma covering all aspects of clinical characteristics of headache including detailed family history. This study will consist of a baseline period of 4 weeks followed by a double-blind treatment phase (DBTP) for 12 weeks and then an open-label treatment phase (OLTP) for another 12 weeks.
The study tests three hypotheses, namely 100mg and 50mg of oral brivaracetam is superior to placebo and 100mg of oral brivaracetam is better than 50 mg of placebo. So , A planned enrolment of 72 patients per treatment group ( BRV 50mg, BRV 100mg, Placebo) shall be done for 3 groups.
METHODS-During the OLTP, the patients will be given an option of continuing with the brivaracetam at a dose of 50-100mg/day for next 12 weeks. Physicians will have discretion to adjust the dose as per the clinical response. After 24 weeks, an attempt to stop the treatment shall be made as per clinical judgement of the investigator. The final follow-up of the patient shall be undertaken at 36 weeks. All patients will be evaluated as per a detailed structured proforma covering all aspects of clinical characteristics of headache including detailed family history. If indicated, contrast enhanced MRI (Brain), Magnetic Resolution Angiography (MRA), Magnetic Resolution Venography (MRV) and Cerebrospinal fluid (CSF) study will be done in selected cases with red flags to rule out a secondary cause. For the detection of psychiatric co-morbidity, a screening questionnaire (PHQ questionnaire) will be used. Depression and anxiety will be rated by Hamilton Depression rating scale (HAM-D) and anxiety by GAD-7. Impact of headache will be assessed by Headache impact test (HIT6) and headache related disability will be assessed by Migraine disability assessment test (MIDAS) and VAS scale for severity of headache. Systemic co-morbid conditions will be noted. There will a baseline phase of 4 weeks followed by DBTP of 5 visits (-0 weeks to 12 weeks) to be followed by OLTP of 3 visits (weeks 16, 20 and 24) .There will be a final visit at 36 weeks following drug withdrawal at 24 weeks. Thus, there will be 10 visits in total.
Efficacy variables such as 4 weekly migraine days, AMT days, CHH, VAS (an 11-item score from 0-10 with higher score indicating greater severity), and 6-item headache impact test (HIT-6) score (higher score indicating greater disability), a 3-dimension migraine specific quality of life (MSQOL) score (higher score indicating worse quality of life), and clinical global impression severity (CGI-S) score that rates the clinician’s view of the patient’s global functioning (higher score indicating greater severity) shall be documented using a paper headache diary at the baseline phase and every subsequent 4 weeks till 12 weeks during DBTP and then during OLTP. Baseline migraine disability assessment score (MIDAS) (a five-item self-administered questionnaire with a higher score indicating greater disability), will be calculated based on 3months data prior to randomization and measured at 12 weeks after randomization. Clinical global impression improvement (CGI-I)score that rates the clinician’s view of the patient’s global improvement following start of treatment (higher score indicating greater worsening) will be measured at 4, 8 and 12 weeks after randomization. Patients will also require reporting telephonically or by what’s app message about the occurrence of any moderate to severe headache and acute treatment taken, if any, on the same day of the attack so that it can be double checked with the filled paper diary later. Statistical analysis will be done with SPSS version 17
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 216
- 1.Adults 18 to 65 years of age who had have a history of migraine with or without aura (as defined by ICHD-3) for at least 12 months before screening.
- 2.Patients should be experiencing at least 4 and fewer than 15 migraine headache days during the 4weeks of the baseline phase (as obtained by the paper headache diary).
- 3.Patients should be experiencing fewer than 15 headache days per month during the last 3 months before baseline the phase (as obtained by history from the patient).
- 4.Patients must demonstrate at least 80% adherence to reporting with the headache diary during the baseline phase.
- 1.Patients older than 50 years at migraine onset.
- 2.Patients will be excluded if they had no therapeutic response in migraine prevention after an adequate therapeutic trial of >2 of the following medication categories: Category 1: Divalproex sodium, sodium valproate; Category 2: Topiramate; Category 3: Beta blockers; Category 4: Tricyclic antidepressants; Category 5: Serotonin-norepinephrine reuptake inhibitors; Category 6: Flunarizine, verapamil; Category 7: Lisinopril, candesartan.
- (No therapeutic response will be defined as no reduction in headache frequency, duration, or severity after administration of the medication for ≥6 weeks at the generally accepted therapeutic dose(s) based on the investigator’s assessment.
- Lack of sustained response to a medication and failure to tolerate a therapeutic dose will not considered to be “no therapeutic response.â€) 3.The following medications, devices, or procedures will be excluded: Botulinum toxin (in the head and/or neck region) is excluded within 4 months before the start of the baseline phase and throughout the study.
- 4.Ergotamine derivatives, steroids, and triptans used for migraine prophylaxis are excluded within 3 months before the start of the baseline phase and throughout the study.
- 5.Devices and procedures used for migraine prophylaxis are excluded within 2 months before the start of the baseline phase and throughout the study.
- Investigational medications and devices are excluded throughout the study.
- 6.Patients also must not have used investigational medications or devices for at least 90 days prior to screening.
- 7.Patients who were concomitantly using medications for migraine prevention within 3 months before the start of the baseline phase and throughout the study will be excluded.
- 8.Patients with significant suicidal ideation as analysed by Columbia Suicide Severity Rating Scale (C-SSRS)>2 9.Pregnant women, female patients who are not willing for effective contraception.
- 10.Patient with known allergies against levetiracetam or brivaracetam, patients with history of moderate to severe anxiety or depression, psychosis and chronic liver, kidney and heart diseases shall be excluded from the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change in mean migraine headache days (MHD) per 28 days compared with baseline at the end of week 12 (migraine day is defined as a calendar day when the patient reported ≥4 continuous hours of headache meeting ICHD 3 criteria for migraine; additionally, any calendar day on which acute migraine–specific medication (ergot or triptan) is used shall be counted as a migraine day. A qualified migraine headache is defined as a migraine with or without aura, lasting for ≥30 minutes, and meeting at least one of the following criteria (a and/or b): a) ≥2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity and b) ≥1 of the following associated symptoms: nausea and/or vomiting, photophobia, and phonophobia) 12 week
- Secondary Outcome Measures
Name Time Method Key Secondary End points 1.Proportions of patients achieving more than 50% reduction in migraine headache days (MHD) per 28 days compared with baseline at the end of week 12
Trial Locations
- Locations (1)
GB Pant Institute of Post Graduate Medical Education and Research
🇮🇳Delhi, DELHI, India
GB Pant Institute of Post Graduate Medical Education and Research🇮🇳Delhi, DELHI, IndiaDr Manju YadavPrincipal investigator8368487948mishty125@gmail.com