Hemin in Healthy Subjects

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00882804
• Other study ID #: 09-000230
• Status: Completed
• Phase: Phase 1
• First received: April 16, 2009
• Last updated: April 16, 2009
• Start date: February 2009
• Est. completion date: April 2009

Study information

• Verified date: April 2009
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous carboxyhemoglobin concentrations		at 6 hours
Primary	HO-1 protein concentration in leukocytes from venous blood		at 6 hours
Primary	Serum bilirubin		at 6 hours
Secondary	Venous carboxyhemoglobin concentrations		at 4, 24, and 48 hours
Secondary	HO-1 activity in leukocytes from venous blood		at 4, 24, and 48 hours
Secondary	Serum bilirubin		at 4, 24, and 48 hours