Combination Treatment of Greater Occipital Nerve Block and Botulinum Toxin for Resistant Migraine: A Randomized Double-Blind Placebo-Controlled Study (COMBO-GONBOT Study))
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Change in mean disabling headache days per 28 days compared with baseline at the end of week 24
研究概览
简要总结
A small but sizeable proportion of migraine patients do not respond to the standard established medications which are called as resistant and refractory migraine as defined by EHF criteria 2020. Currently the treatment options for resistant migraine include BoT-A, GON blocks and anti-CGRP mAbs. However when used alone they are efficacious in only about 50% of the patients. Hence, combination treatments are being tried. A combination of anti-CGRP mAbs and BoT-A is very expensive and is prohibitive for most of the patients in the developing world. In contrast, GONB treatment is very cheap, easily available and require little expertise to administer. Efficacy and tolerability of a combination treatment of GONB and BoT-A for prevention of resistant migraine is unknown.Hence, this randomized controlled trial (RCT) was devised using the International Headache society guidelines to find the efficacy and the tolerability of the combination of GONB and BoT-A in patients with resistant migraine.
Aims of this study are:
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1.To find out the efficacy of combination treatment of 4 weekly GONB with 12 weekly BoT-A at 24 weeks for the prevention of resistant migraine as compared with either treatment as monotherapy.
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To find out the effects of combination treatment of 4 weekly GONB with 12 weekly BoT-A at 24 weeks on patient reported outcomes such as headache impact, disability, and migraine specific quality of life. 3. To find out the tolerability of combination treatment of 4 weekly GONB with 12 weekly BoT-A at 24 weeks for the prevention of resistant migraine as compared with either treatment as monotherapy.
Methodology:
This randomized, double-blind, placebo-controlled, parallel-group study will consist of a baseline period of 4 weeks followed by a double-blind treatment phase (DBTP) for 24 weeks. There will be three intervention groups during the DBTB: Group A: GONB with BoT-A, Group B: GONB and sham BoT-A (using normal saline), Group C: BoT-A with sham GONB (using normal saline). Following the screening of eligible patients, the baseline data (4 weeks) will be captured by using the headache diary. Randomization shall be done by computer-based block randomization chart and patients will be allocated to the three intervention groups. The patients will be followed up for 24 weeks. The primary end point would be Change in mean disabling headache days per 28 days compared with baseline at the end of week 24. Efficacy variables such as 4 weekly disabling headache days, migraine days, AMT days, CHH, pain severity [rated by numeric rating scale (NRS); higher score denoting greater severity of pain], 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 24 weeks during DBTP. 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 and 24 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 12 and 24 weeks after randomization.Acute migraine treatment (acetaminophen, NSAIDs, antiemetics, triptans, ditans and ergots) shall be allowed throughout the study. The patients shall be told to take acute medication after 30 minutes of onset of moderate to severe headache attacks. They will be also educated to reduce the medication overuse and be encouraged to use stratified acute care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Adults 18 to 65 years of age who had have a history of migraine with or without aura (as defined by ICHD-3)12 for at least 12 months before screening and fulfils the European Headache Federation (EHF) consensus criteria for resistant migraine.
- •Patients should be experiencing ≥8 days/month of disabling headache for at least 3 months (as defined by EHF criteria).
- •Patients with failure to three treatment classes of drugs (with established evidence for migraine prevention) given at an appropriate dose for an appropriate duration (as defined by EHF consensus criteria).
- •Patients with medication overuse [overuse of triptans, ergot derivatives, analgesics, and combination drugs (any combination of those above or simple analgesics with opiates or butalbital)] will be permitted to participate in this study.
排除标准
- •Patients older than 50 years at migraine onset
- •Patients who have previously received and failed BoT-A and GONB treatments during the last 6 months or less prior to the inclusion.
- •Patients who had previously received anti-CGRP-mAbs three months or less before their enrolment.
- •Patients who had received neuromodulation devices and undergone procedures such as multiple nerve blocks used for migraine prophylaxis.
- •Patients who had received investigational medications and devices for migraine prevention.
- •All patients with a clinical phenotype of episodic or chronic migraine but on further investigation, found to have a secondary cause for their headaches will be excluded.
- •Pregnant women, patients with known allergies against lidocaine or BoT-A, patients with history of moderate to severe anxiety or depression, psychosis and chronic liver, kidney and heart diseases.
结局指标
主要结局
Change in mean disabling headache days per 28 days compared with baseline at the end of week 24
时间窗: 24 weeks
次要结局
- Proportions of patients achieving more than 50% reduction in disabling headache days per 28 days compared with baseline at the end of week 24(24 weeks)
- Change in mean migraine days per 28 days compared with baseline at the end of week 24. (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)(24 weeks)
- Change in mean number of acute migraine treatment (AMT) days to abort the headache attacks (analgesics/triptans/ergotamines) per 28 days compared with baseline at the end of week 24(24 weeks)
- Change in mean total duration of disabling headache [cumulative headache hours (CHH)] per 28 days compared with baseline at the end of week 24(24 weeks)
- Change in mean Numerical Pain Rating Scale per 28 days compared with baseline at the end of week 24(24 weeks)
- Change in mean HIT-6 (Headache Impact Test) score per 28 days compared with baseline at the end of week 24(24 weeks)
- Change in mean MIDAS (Migraine Disability Assessment) score per 28 days at the end of week 24(24 weeks)
- Change in migraine specific quality of life score per 28 days compared with baseline at the end of week 24(24 weeks)
- Change in clinical global impression severity (CGI-S) score per 28 days compared with baseline at the end of week 24(24 weeks)
- Clinical global impression improvement (CGI-I) score per 28 days at the end of week 24(24 weeks)
- Proportions of patients in each group having treatment emergent adverse events including serious adverse events at the end of week 24(24 weeks)
研究者
Dr Debashish Chowdhury
GB Pant Institute of Postgraduate Medical Education and Research, New Delhi