In Vitro Basophil Responsiveness to Allergen Challenge After Gamma-tocopherol Supplementation in Allergic Asthmatics (Gammaphil)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00836368|
Recruitment Status : Completed
First Posted : February 4, 2009
Last Update Posted : November 7, 2011
Purpose: This is a non-masked study with a primary endpoint of in vitro basophil activation by the allergen D. farinae, comparing basophil activation before and after seven days of supplementation. Secondary endpoints will include circulating antioxidant levels (tocopherols and metabolites), in vitro basophil activation to IgG anti-IgE and to N-formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe), and monocyte and basophil responsiveness to in vitro endotoxin challenge.
Participants: Twenty allergic asthmatic volunteers Procedures (methods): Volunteers will be given 1200 mg of a gamma tocopherol enriched supplement, a commercially available supplement form of vitamin E. Study participants will undergo assessment of general health, lung function assessment, symptom scoring, and epicutaneous skin test to allergens at baseline and after supplementation. Blood samples will be collected at baseline and after 7 days of gamma-T treatment.
|Condition or disease||Intervention/treatment||Phase|
|Allergic Asthmatic Allergy Asthma||Dietary Supplement: gamma-tocopherol||Phase 1|
Oxidant stress plays an important role in mucosal inflammation such as seen with asthma. Previous studies have also shown that asthmatic individuals tend to have lower endogenous levels of antioxidant such as vitamins E and C, and that supplementing antioxidants can decrease exacerbations associated with ozone exposure in children. We are interested in future studies to examine the benefits of gamma-tocopherol supplementation for people with allergic asthma. This current study will determine if gamma tocopherol supplementation reduces allergic responses in vitro, providing us information that will allow us to design future masked placebo-controlled studies of this potentially important antioxidant on in vivo allergic responses.
The purpose of this study is to address the question if in vivo gamma-tocopherol supplementation at 1200 mg daily blunts allergen-specific inflammatory responses in vitro. Members of our group have previously shown that administration of 100 mg/kg of gamma tocopherol daily for four days prior to Ova challenge in sensitized allergic brown Norway rats prevented eosinophil infiltration into the airways1. In addition, this dose of gamma tocopherol blunted production of IL-4, IL-5, IL-13, IFN-gamma in the nasal airway; and PGE2, LTB4 and cysteinyl leukotrienes by the pulmonary airway. Mucous cell metaplasia was decreased as well in the gamma Tocopherol treatment group 1. In an in vivo study of gamma tocopherol performed at our center (IRB# 05-CEMALB-1407), we found that daily administration of 2 capsules of a gamma tocopherol rich preparation (each capsule containing 623 mg of gamma tocopherol, 61.1 mg of d-alpha-tocopherol, and 11.1 mg of d-beta tocopherol), was able to increase serum levels of gamma tocopherol to 18.6 + 2.6 uM after 8 days of daily administration; serum levels of alpha tocopherol were 25.2 + 2.4 uM, and delta-tocopherol were 5.1 + 1.1 uM2 . Using the data from the in vivo study, we performed basophil activation tests on dust mite allergic subjects, pretreating blood obtained from venipuncture with pharmacologic doses attained in the vivo study with gT, aT, gCEHC, and aCEHC. We found that gT, gCEHC, and aCEHC blunted basophil activation induced by the allergen D. farinae, as measured by upregulation of CD63 on the cell surface of basophils. As secondary aims, we will also examine the effect of gamma tocopherol supplementation on non-allergic stimuli that have been shown to activate basophils, such as IgG anti-IgE and N-formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe), as well as in vivo allergen-specific responsiveness through epicutaneous skin testing before and after supplementation. Exploratory analyses will include assessing the effect of gamma tocopherol supplementation on monocyte and basophil responsiveness to in vitro endotoxin and lipoteichoic acid challenge.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||In Vitro Basophil Responsiveness to Allergen Challenge After Gamma-tocopherol Supplementation in Allergic Asthmatics|
|Study Start Date :||December 2008|
|Primary Completion Date :||December 2010|
|Study Completion Date :||December 2010|
Dietary Supplement: gamma-tocopherol
oral doses 1,200 mg of gamma tocopherol (2 capsules of the gamma tocopherol enriched vitamin E preparation)
Other Name: Vitamin E
- We intend to examine the effect of once daily oral doses 1,200 mg of gamma tocopherol (2 capsules of the gamma tocopherol enriched vitamin E preparation) on in vitro basophil activation with D. farinae challenge. [ Time Frame: 7 sdays post gamma-tocopherol treatment ]
- Circulating antioxidant levels(tocopherols and metabolites), in-vitro basophil activation to IgG anti-IgE and to N-formyl-methionyl-leucyl-phenylalanine. [ Time Frame: 7 days post gamma-tocopherol treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00836368
|United States, North Carolina|
|Center for Environmental Medicine Asthma and Lung Biology|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||Michelle Hernandez, MD||University of North Carolina, Chapel Hill|