Hemin in Healthy Subjects

Study Overview
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Brief Summary
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This study is being done because we want to learn if hemin can increase the production of heme oxygenase 1. Heme oxygenase 1 (HO-1) is an enzyme which protects cells from physical, chemical, and biologic stress. Hemin is produced from red blood cells and is approved by the Food and Drug Administration for treating acute porphyria, which is an inherited condition caused by an enzyme deficiency.

Detailed Description
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Heme-oxygenase 1 (HO-1) degrades heme, protects cells against oxidative stress, and is beneficial in several experimental models but has not been pharmacologically activated in humans. The objectives of this study were to evaluate the effects of hemin on HO-1 activity in healthy subjects. Hemin is the most powerful inducer of HO-1. Hemin is FDA-approved to treat acute intermittent porphyria. In addition, hemin has also been used to treat thalassemia intermedia, myelodysplastic syndrome, and to control liver allograft failure due to recurrence of erythropoietic prototheria. Our hypothesis is that compared to placebo, hemin will increase HO-1 in humans. Ten healthy subjects will be randomized to hemin (n = 5, Panhematin®, Ovation Pharmaceuticals, 3 mg/kg i.v. in 25% albumin) or placebo (n = 5, 25% albumin) infusion. HO-1 activity will be assessed before and after (4, 6, 24, and 48 hours) infusions.

Official Title
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Effect of Hemin on Heme-Oxygenase-1 Activity in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Hemin infusion
* Drug: placebo infusion


Participation Criteria
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Eligibility Criteria
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Healthy non pregnant not breast feeding, and non-smoking subjects aged 18 - 65 years old without clinical evidence of significant cardiovascular, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns. No symptoms of functional GI disorder as assessed by a validated questionnaire. No medications except for stable doses of oral contraceptives or thyroid supplementation. Because ascorbic acid can induce HO-1 activity, multivitamins will need to be discontinued for 1 week before and for the duration of the study. No intolerance or allergy to eggs Able to provide written informed consent before participating in the study Able to communicate adequately with the investigator and to comply with the requirements for the entire study Screening weight < 96 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemin<br> | Drug: Hemin infusion<br>* Hemin (Panhematin®, Ovation Pharmaceuticals, Deerfield, IL) will be administered through a large-caliber peripheral vein at a dose of 1.25 mL/kg and at a rate of 60 mL/hour. To enhance stability, Panhematin® will be diluted in   132 mL of 25% albumin to obtain a hemin concentration of 2.4 mg/mL.<br>|
| Placebo Comparator: placebo<br> | Drug: placebo infusion<br>* 25 % albumin will be administered through a large-caliber peripheral vein at a dose at a rate of 60 mL/hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous carboxyhemoglobin concentrations |  | at 6 hours | 
| HO-1 protein concentration in leukocytes from venous blood |  | at 6 hours | 
| Serum bilirubin |  | at 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous carboxyhemoglobin concentrations |  | at 4, 24, and 48 hours | 
| HO-1 activity in leukocytes from venous blood |  | at 4, 24, and 48 hours | 
| Serum bilirubin |  | at 4, 24, and 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemin, heme oxygenase, humans, HO-1