Measuring the effects of L-arginine and aged garlic extract on migraine in Australian adults

INTERVENTION: We compare L‐arginine and aged garlic extract (AGE) as separate systemic vasodilating agents to see which (if either) is more effective in preventing migraines. We assess whether any of these comparators have differing efficacies in different aspects of the headache, such as frequency, duration or severity. Each subject will self‐administer the treatments as follows: 2500 mg/day placebo as oral capsules for the first 2 weeks, then their allocated treatment (placebo oral capsules, 1500 mg/day L‐arginine oral capsules, 1000 mg/day AGE oral capsules, or both as oral capsules) for the next 12 weeks. Participants are required to return the initial capsule bottle (placebo capsules provided at week 1) at the baseline visit (week 3). Eighty percent compliance is required to continue in the study to ensure compliance during treatment. Participants are also contacted one week following commencement of treatment to discuss any potential adverse events and treatment compliance. Participants are required to return their treatment capsule bottle(s) at the end of week 14 (post‐intervention) visit to monitor adherence. CONDITION: Migraine; ; Migraine Neurological ‐ Other neurological disorders PRIMARY OUTCOME: To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on migraine frequency in migraineurs, over 14 weeks; Measured via daily headache diaries[Daily over the 14 weeks] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on photosensitivity in migraineurs, over 14 weeks; Measured via photosensitivity test[ At Weeks 3 (baseline) and 14 (immediate post‐intervention)] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on quality of life in migraineurs, over 14 weeks; Measured via Migraine‐Specific Quality‐of‐Life Questionnaire (MSQ)[At Weeks 1 (pre‐baseline) and 14 (immediate post‐intervention)] SECONDARY OUTCOME: Primary outcome: To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on migraine severity in migraineurs, over 14 weeks ; Measured using the Short‐Form McGill Pain Questionnaire (SF‐MPQ)[,At Weeks 1 (pre‐baseline) and 14 (immediate post‐intervention)] Primary outcome: To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on migraine severity in migraineurs, over 14 weeks ; Measured via daily headache diaries[Daily over the 14 weeks] Primary outcome: To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on photosensitivity in migraineurs, over 14 weeks as measured by the Leiden Visual Sensitivity Scale (L‐VISS)[At weeks 1 (pre‐baseline) and 14 (immediate post‐intervention)] Primary outcome: To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on photosensitivity in migraineurs, over 14 weeks using the Visual Light Sensitivity Questionnaire – 8 (VLSQ‐8)[At weeks 1 (pre‐baseline) and 14 (immediate post‐intervention)] To examine the adverse effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on the body in migraineurs, over 14 weeks ; Measured via optical coherence tomography angiography (OCTA) scans of left and right eyes [At Weeks 3 (baseline) and 14 (immediate post‐intervention)] INCLUSION CRITERIA: 1. Migraine (with or without aura) diagnosed at least 1 year ago 2. Migraine onset occurred before 50 years of age 3. 2‐6 migraine episodes and fewer than 6 'other' headache types per month, over the last 3 months 4. Able to distinguish between migraine and 'other' headache types 5. Able to complete a daily diary about migraine experience 6. Able to commit to taking the 5 capsules a day for 14 weeks ; Examined via reporting of quantity and quality of adverse effects by participants and graded according to the NCI‐CTCAE v5 (or higher)[Daily reporting throughout 14‐week duration of trial] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on blood biomarkers of vascular tone in migraineurs, over 12 weeks ; Measured via enzyme‐linked immunological (ELISA) assay for symmetric dimethylarginine (SDMA)[Fasted blood samples collected at Weeks 3 (baseline) and 14 (immediate post‐intervention) will be analysed ] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on blood biomarkers of vascular tone in migraineurs, over 12 weeks ; Measured via enzyme‐linked immunological assay (ELISA) for asymmetric dimethylarginine (ADMA)[Fasted blood samples collected at Weeks 3 (baseline) and 14 (immediate post‐intervention) will be analysed ] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on blood biomarkers of vascular tone in migraineurs, over 12 weeks ; Measured via enzyme‐linked immunological assay (ELISA) for endothelin‐1[Fasted blood samples collected at Weeks 3 (baseline) and 14 (immediate post‐intervention) will be analysed ] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on blood biomarkers of vascular tone in migraineurs, over 12 weeks ; Measured via enzyme‐linked immunological assay (ELISA) for nitrites and nitrates[Fasted blood samples collected at Weeks 3 (baseline) and 14 (immediate post‐intervention) will be analysed ] To measure the effects of 1500 mg/day L‐arginine and/or 1000 mg/day aged garlic extract (AGE) on retinal vascular diameter in migraineurs, over 12 weeks