Efficacy of L-arginine and combination with garlic extract for migraine prevention in Australian adults

INTERVENTION: Arm 1 (comparator arm); oral capsules of 1.5 g L‐arginine (L‐arg) daily for 8 weeks, then 1.5 g L‐arginine + 0.2 g placebo daily for 8 weeks (temporally separated) Arm 2 (intervention arm): oral capsules of 1.5 g L‐arginine daily for 8 weeks, then 1.5 g L‐arginine + 0.2 g garlic extract (GE) daily for 8 weeks (temporally separated) To monitor adherence, capsule counts will be done by the investigatory team when the participants return their capsule bottles on their subsequent visit (they will have been asked to do so). The first 8 weeks of each arm are open‐label, in that both investigator and participant know they are receiving L‐arginine. The next 8 weeks will be double‐blind, in that participants will have been randomised to either arm at enrolment, and neither investigator nor participant know which of garlic extract or placebo they will be receiving on top of their L‐arginine. CONDITION: Chronic frequent episodic migraine; ; Chronic frequent episodic migraine Neurological ‐ Other neurological disorders PRIMARY OUTCOME: Migraine pain type with frequency [Short‐form McGill Pain Questionnaire Baseline, every 2 weeks over the 16‐week study, end of study (primary endpoint)] Migraine severity [VAS scale in Short‐form McGill Pain Questionnaire Baseline, every 2 weeks over the 16‐week study, end of study (primary endpoint)] Migraine‐related quality of life ; [Migraine‐Specific Quality‐of‐Life Questionnaire (MSQ) Baseline, every 4 weeks over the 16‐week study, end of study (primary endpoint)] SECONDARY OUTCOME: Concentration of blood asymmetric dimethyl‐arginine taken from antecubital fossa [Enzyme‐linked immunosorbent assay (ELISA) ; Baseline, every 8 weeks over the 16‐week study, end of study ] Concentration of blood endothelin 1 taken from antecubital fossa [Enzyme‐linked immunosorbent assay Baseline, every 8 weeks over the 16‐week study, end of study ] Concentration of blood nitrite taken from antecubital fossa [Enzyme‐linked immunosorbent assay (ELISA) Baseline, every 8 weeks over the 16‐week study, end of study] Unexpected effects of our treatment [Unexpected Effects From Your Capsules questionnaire. Devahuti Chaliha developed it for this study. Every 4 weeks over the 16‐week study, end of study ] INCLUSION CRITERIA: 1. Migraine (with or without aura) diagnosis at least 12 months ago 2. Migraine onset occurred before 50 years of age 3. Males and females, aged at least 18 years at screening 4. At least one migraine a week, averaged over the previous 3 months 5. Able to differentiate between migraine and “other” headache types