Hemin in Healthy Subjects

Effect of Hemin on Heme-Oxygenase-1 Activity 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 Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Hemin infusion; Drug: placebo infusion

Detailed Description

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
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
Experimental: Hemin	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Mayo Clinic

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: April 16, 2009
• First Submitted That Met QC Criteria: April 16, 2009
• First Posted (Estimate): April 17, 2009

Study Record Updates

• Last Update Posted (Estimate): April 17, 2009
• Last Update Submitted That Met QC Criteria: April 16, 2009
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: hemin, heme oxygenase, humans, HO-1
• Other Study ID Numbers: 09-000230