Hemin in Healthy Subjects

Mayo Clinic10 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

TRIPLE

Enrollment

Conditions

Healthy Volunteers

Interventions

Hemin infusionDRUG

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 infusionDRUG

25 % albumin will be administered through a large-caliber peripheral vein at a dose at a rate of 60 mL/hour.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

1. 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. 2. 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. 3. No intolerance or allergy to eggs 4. Able to provide written informed consent before participating in the study 5. Able to communicate adequately with the investigator and to comply with the requirements for the entire study 6. Screening weight \< 96 kg

Locations (1)

Mayo Clinic

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

Data from ClinicalTrials.gov

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