Modulation of Cerebral Blood Flow Using Iron Chelators

Study Overview
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Brief Summary
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The purpose of this study is determine if the iron chelator, desferrioxamine can increase blood levels of hypoxia-inducible transcription factor 1 (HIF-1 protein) and to see if there is a corresponding increase in blood flow to the brain.

Official Title
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Hypoxia-Inducible Transcription Factor 1 (HIF-1)in Vascular Aging

Conditions
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Stroke, Problem of Aging

Intervention / Treatment
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* Drug: desferrioxamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy adults between the ages of 18-80 years. Exclusion Criteria: subjects taking vasoactive medications, hypertension, pregnant women, smokers, COPD, asthma, diabetes mellitus, intracranial or carotid stenosis, hepatic disease, renal disease, bone marrow suppression, cardiac disease, heart failure, iron deficiency, history of cancer, history of head trauma, subarachnoid hemorrhage, central nervous system vasculitis, multiple sclerosis, migraines, seizures, sickle cell disease or trait, cardiac arrhythmia, unable to give informed consent, or poor transcranial Doppler insonation windows.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy young<br>Each subject comes for 2 visits. There is a randomized, double-blind, crossover design so each subject will receive active drug during one visit and placebo during the other. | Drug: desferrioxamine<br>* intravenous infusion at 10mg/kg/hr for a total of 6 hours at final infused doses of 60mg/kg.<br>* Other names: Desferal, desferoxamine;|
| Experimental: healthy old<br>Each subject comes for 2 visits. There is a randomized, double-blind, crossover design so each subject will receive active drug during one visit and placebo during the other. | Drug: desferrioxamine<br>* intravenous infusion at 10mg/kg/hr for a total of 6 hours at final infused doses of 60mg/kg.<br>* Other names: Desferal, desferoxamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define change from baseline cerebral blood flow after receiving DFO infusion. | Cerebral blood flow is measured with transcranial Doppler ultrasound at baseline and then study drug is initiated. Blood flow is measured again after 3 hours of infusion, 6 hours of infusion, then once more 3 hours after the infusion is complete. | baseline, 3hr, 6hr, 9hr | 
| Determine if DFO changes blood HIF-1 levels from baseline and whether this correlates with changes in cerebrovascular hemodynamics. | Blood samples are taken at each time point and will be correlated with ultrasound blood flow measures taken at baseline, 3hrs of infusion, 6hrs of infusion, and 3 hours after infusion is complete. | baseline, 3hr, 6hr, 9hr | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain blood flow, stroke, cerebrovascular, aging, cerebrovascular hemodynamics