In Vitro Basophil Responsiveness to Allergen Challenge After Gamma-tocopherol Supplementation in Allergic Asthmatics
Condition: Allergic; Asthmatic; Allergy; Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): gamma-tocopherol
Intervention type(s): Dietary Supplement
Intervention description(s): oral doses 1,200 mg of gamma tocopherol (2 capsules of the gamma tocopherol enriched vitamin E preparation)
Other intervention name(s): Vitamin E
Intervention MeSH terms: Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; gamma-Tocopherol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Asthma; Asthmatic; Allergy; Allergic; Gamma-tocopherol; Vitamin; Vitamin E