Effect on Migraine Frequency of Combined Anti-oxidant Therapy: N-acetylcysteine, Vitamin E and Vitamin C (NEC): The MIGRANT Study
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 90
- 主要终点
- Difference in mean number of migraine episodes per month between baseline and final four weeks of the study, for both study groups.
研究概览
简要总结
Migraine affects 15% of Western Australians and is a leading cause of suffering and disability in our community (1,2). Research suggests that inflammation of the brain's coverings (meninges) by nerve cell inflammation and the release of 'free radicals', is a cause of migraine. N-acetylcysteine, Vitamin E and Vitamin C are powerful anti-oxidants (free-radical scavengers) that reduce brain inflammation and nerve activity. It is therefore possible these anti-oxidants could reduce the number and severity of migraines. We will study 90 subjects to see if a combination of N-acetylcysteine 600 mg, Vitamin E 250 IU and vitamin C 500 mg (NEC) taken twice daily for 3 months, will reduce migraine attacks. This safe vitamin-based therapy has never been studied and if effective, will play an important role in migraine prevention.
详细描述
Summary:
Migraine affects 15% of Western Australians and is a leading cause of suffering and disability in our community. Research suggests that inflammation of the brain's coverings (meninges) by nerve cell inflammation and the release of 'free radicals', is a cause of migraine. N-acetylcysteine, Vitamin E and Vitamin C are powerful anti-oxidants (free-radical scavengers) that reduce brain inflammation and nerve activity. It is therefore possible these anti-oxidants could reduce the number and severity of migraines. We will study 90 subjects to see if a combination of N-acetylcysteine 600 mg, Vitamin E 250 IU and vitamin C 500 mg (NEC) taken twice daily for 3 months, will reduce migraine attacks. This safe vitamin-based therapy has never been studied and if effective, will play an important role in migraine prevention.
Because migraine is a complex neuro-vascular-inflammatory disorder with a 'cascade' of steps, there are many potentially targets for drug prophylaxis. Research highlights the importance brain neuro-inflammation mediated by Calcitonin Gene Related Peptide (CGRP) and Substance P (SP), and oxygen and nitrogen free radical species (FRS) (eg. nitric oxide [NO]) in the pathogenesis of migraine. Increased levels of NO and CGRP were found in the jugular venous blood migraineurs and NO produces cerebral vasodilation, which is a key step in migraine generation. Furthermore, FRS activate the trigeminal-cervical nucleus (TCN) which is the main centre of nociceptive (pain) sensitization in headaches-Sumatriptan blocks this process accounting for some of its anti-migraine effect.
Anti-oxidants such as N-acetylcysteine (NAc), Vitamin C (ascorbic acid) (VitC) and Vitamin E (alpha-tocopherol) (VitE) are potent FRS 'scavengers', which means they could be used to prevent migraine. Two small non-randomised trials suggested that antioxidants reduced migraine frequency and disability. Like sumatriptan, NAc reduces activation of the TCN by NO, also neuro-inflammation in brain disorders such as Parkinson's disease. VitC and VitE reduced NO levels in mice and VitC enhanced the neuro-inhibitory effects of gamma amino butyric acid in the central nervous system-This mechanism could conceivably interrupt 'spreading cortical activation' which is the first step in the migraine cascade.
Migraineurs have an increased risk of developing an analogous neuro-inflammatory disorder, Complex Regional Pain Syndrome (CRPS); increased plasma levels of SP, CGRP and FRS were found in patients with these conditions. CRPS responds to treatment with NAc and VitC. A meta-analysis found that combined (but not single-agent) anti-oxidant therapy (CAT) was safe and effective in treating chronic pancreatitis, an inflammatory pain disorder similar to both CRPS and migraine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Migraine (with or without aura) according to IHS 2013 criteria.
- •Migraine of at least one year's duration, with onset before 50 years of age.
- •Two-to-eight migraine episodes, and less than six 'other' headache types per month, averaged over 12 weeks prior to recruitment.
- •Subjects able to clearly distinguish between migraine and 'other' headache types.
- •Cognitive and English language skills allowing completion of headache diaries and self-administration of trial drugs.
排除标准
- •Participation in a concurrent research trial.
- •Chronic daily headaches, according to IHS 2013 criteria.
- •Medication-overuse headache and/or other primary headache disorders, according to IHS 2013 criteria.
- •Change in migraine treatment in the twelve weeks prior to, or during the study.
- •Taking ≥ 2 migraine prevention drugs.
- •Failure to respond in ≥ 2 previous migraine prevention trials.
- •Taking NAc, VitE or VitC supplements in the 12 weeks prior to the study.
- •Pregnancy, or risk of pregnancy during the study; female of reproductive age not taking medically prescribed contraception; breast feeding.
- •Adverse reactions to NAc, VitE or VitC preparations; VitC deficiency.
- •Renal dysfunction (eGFR ≤ 30 ml/min/1.73m2), liver dysfunction (ALT or AST > 300 IU/L).
- •Clinical risks associated with bleeding, coagulopathy, warfarin therapy.
- •Haemochromatosis, glucose-6-phosphate dehydrogenase deficiency.
- •Daily opioid use in the 12 weeks prior to or during the study.
- •Substance abuse, dependence or addiction during the study.
- •Psychosis, bipolar affective disorder.
研究组 & 干预措施
Active-verum-NAC tablet
Intervention: Twice-daily administration of N-acetyl cysteine 600 mg, VitE 250 IU, VitC 500 mg tablets
干预措施: N-acetyl cysteine 600 mg, VitE 250 IU, VitC 500 mg tablet (Drug)
Sham-placebo tablet
Intervention: Twice daily administration of sham/placebo tablet
干预措施: N-acetyl cysteine 600 mg, VitE 250 IU, VitC 500 mg tablet (Drug)
结局指标
主要结局
Difference in mean number of migraine episodes per month between baseline and final four weeks of the study, for both study groups.
时间窗: 16 weeks
Difference in mean number of migraine episodes per month between baseline and final four weeks of the study, for both study groups.
次要结局
- Difference in mean migraine duration (hours) per month between baseline and final four weeks of the study, for both study groups(16 weeks)
- Difference in mean migraine severity score per month (categorical scale; 0 = nil, 1 = mild, 2 = moderate, 3 = severe) between baseline and final four weeks of the study, for both study groups.(16 weeks)
- Difference in mean MIDAS per month between baseline and final four weeks of the study, for both study groups.(16 weeks)
- Difference in mean MSQ score per month between baseline and final four weeks of the study, for both study groups. Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1) score.(16 weeks)
- Difference in mean HRQOL score per month between baseline and final four weeks of the study, for both study groups.Health Related Quality of Life (HRQOL) score(16 weeks)
- Number of treatment adverse events per month Number and type of treatment-related adverse effects per month. Number and type of treatment-related adverse effect(16 weeks)
- Difference in mean number of migraine days per month between baseline and final four weeks of the study, for both study groups.(16 Weeks)
- Responder rate: Percentage of subjects reporting ≥ 30% reduction in migraine episodes per month between baseline and final four weeks of the study, for both study groups(16 weeks)
研究者
Professor Eric Visser
Professor Eric J Visser
University of Notre Dame Australia