Clinical trial NCT00882804: Hemin in Healthy Subjects
Official title: Effect of Hemin on Heme-Oxygenase-1 Activity in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: hemin, heme oxygenase, humans, HO-1
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2009-04-17
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Venous carboxyhemoglobin concentrations
timeFrame: at 6 hours
measure: HO-1 protein concentration in leukocytes from venous blood
timeFrame: at 6 hours
measure: Serum bilirubin
timeFrame: at 6 hours
Secondary outcomes:
measure: Venous carboxyhemoglobin concentrations
timeFrame: at 4, 24, and 48 hours
measure: HO-1 activity in leukocytes from venous blood
timeFrame: at 4, 24, and 48 hours
measure: Serum bilirubin
timeFrame: at 4, 24, and 48 hours
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adil E Bharucha, M.D.
role: PRINCIPAL_INVESTIGATOR
References: