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

Study Overview
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Brief Summary
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To measure the cerebral hemodynamic effect of L-kynurenine.

Detailed Description
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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.

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

Conditions
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Headache

Intervention / Treatment
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* Drug: L-kynurenine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Pilot, Open label
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: L-kynurenine|intravenous infusion of L-kynurenine to healthy individuals.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Velocity of MCA (VMCA) | Measured in MCA (middle cerebral artery) bilaterally with ultrasound (TCD) (2 Mhz, DWL) | Change from baseline VMCA at two hours after administration of L-kynurenine | 
| The diameter of the STA (superficial temporal artery) | Measured by high-frequency ultrasound 12 of 29 (Derma Scan C, Cortex Technology, Denmark) | Change from baseline VMCA at two hours after administration of L-kynurenine | 
| Headache | Headache declared orally on a verbal rating scale (VRS) 0-10. 0 represents no pain and 10 the worst possible headache. | occurrence of headache undtil 24 hours after infusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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L-kynurenine, Cerebral hemodynamic, Headache, Mohammad Al-Mahdi Al-Karagholi