Hemin in Healthy Subjects
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
|Official Title:||Effect of Hemin on Heme-Oxygenase-1 Activity in Healthy Subjects|
- Venous carboxyhemoglobin concentrations [ Time Frame: at 6 hours ]
- HO-1 protein concentration in leukocytes from venous blood [ Time Frame: at 6 hours ]
- Serum bilirubin [ Time Frame: at 6 hours ]
- Venous carboxyhemoglobin concentrations [ Time Frame: at 4, 24, and 48 hours ]
- HO-1 activity in leukocytes from venous blood [ Time Frame: at 4, 24, and 48 hours ]
- Serum bilirubin [ Time Frame: at 4, 24, and 48 hours ]
|Study Start Date:||February 2009|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Drug: Hemin infusion
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.
|Placebo Comparator: placebo||
Drug: placebo infusion
25 % albumin will be administered through a large-caliber peripheral vein at a dose at a rate of 60 mL/hour.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00882804
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Adil E Bharucha, M.D.||Mayo Clinic|