The Effect of Intravenous L-kynurenine (LKYN) on Cerebral Hemodynamics in Healthy Volunteers

Aim: To investigate the physiological effect of L-Kynurenine after intravenous administration to healthy volunteers. Hypothesis: L-kynurenine induces vasodilation in the cerebral vessels and trigger headache in healthy individuals. Methods: 6 healthy volunteers will receive intravenous infusion of L-kynurenine using the following doses 50 microgram/kg, 100 microgram/kg, 150 microgram/kg, 300 microgram/kg, 500 microgram/kg, 1 mg/kg and 5 mg/kg over 20 min on 7 different days with at least 1 day in between. Before and after infusion (at 20, 40, 60, 80 and 100 min) we will record vital signs, circumferences of middle cerebral artery, superficial temporalis artery and headache intensity and characteristics. The subjects will then have a questionnaire about headache for the following 24 hours.

Headache declared orally on a verbal rating scale (VRS) 0-10. 0 represents no pain and 10 the worst possible headache.

Inclusion Criteria: Healthy volunteers of both sexes. 18-60 years. 50-90 kg. Women of childbearing potential must use adequate contraception. Exclusion Criteria: All primary headaches First-degree relative with migraine Headache less than 48 hours before the tests start Daily consumption of drugs of any kind other than oral contraceptives. Pregnant or nursing women. Cardiovascular disease of any kind, including cerebrovascular diseases.

1. Using a controlled access approach, using a transparent and robust system to review requests and provide secure data access; 2. seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and 3. Establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD