Effects of Plant Stanols on Immune Function in Asthma Patients
Condition: Asthma; Allergy
MeSH terms: Asthma
Study type: Interventional

Summary: 
      Rationale: Plant stanols are well known for their effects on lowering intestinal cholesterol
      absorption ultimately resulting in 10-15% reduced serum LDL cholesterol concentrations in
      humans. In addition we have also shown that serum triacylglycerol (TG) concentrations may be
      lowered in subjects with elevated baseline concentrations. Till now, there is little evidence
      for plant stanol effects other than improving lipid profiles. However, we have very recently
      found strong indications in ex vivo models using isolated human peripheral mononuclear blood
      cells (PBMCs) from healthy volunteers that plant stanols have the capacity to improve immune
      function. More into detail, plant stanols shifted the differentiation of naive T-cells into
      the Th1 direction by activating a specific receptor present on the Antigen presenting cells
      (APCs) and T-cells. This effect might ultimately be helpful in situations in which the
      Th1/Th2 cell balance is disturbed into a Th2 over-responsiveness. By activating the Th1
      response, the disturbed balance may be restored. This is for example a possibility in the
      treatment or prevention of asthma, food allergies or HIV in susceptible subjects. In
      addition, very recently (MEC 08-3-051) in a pilot study we also showed these ex vivo Th1
      stimulating effects of plant stanols specifically in PBMCs isolated from asthma patients, as
      said, a condition characterized by a Th2 dominant immune response.

      Objective: The major research objective is to prove that the consumption of plant stanol
      ester enriched yogurts can improve immune function in vivo in asthma patients.

      Study design: A double-blind randomized placebo-controlled human intervention study in which
      90 patients with clinically proven asthma will participate: 45 in the intervention group
      receiving plant stanol yoghurt and 45 in the control group receiving a control yoghurt
      without added plant stanols. At the end of the run-in period as well as at the end of the
      experimental period blood will be sampled to isolate PBMCs. These cells are used to evaluate
      effects on cytokine production, phagocytic capacity of neutrophils, and the activity of NK
      cells. In addition, the golden standard to show improvements in immune function is by showing
      an elevated Immunoglobulin response to a vaccine. Therefore, during the experimental period
      all subjects receive a vaccination against Hepatitis A Virus. After 1, 2, 3, and 4 weeks
      blood will be sampled to monitor specific immunoglobulin titers to HAV.

      Study population: 90 people with clinically proven asthma, who are not carrier of hepatitis
      A, B or C and have not been vaccinated against hepatitis A in the past. Also, these
      participants do not have any other immune-related pathology Main study parameters/endpoints:
      primary: Specific anti-HAV antibody titers after vaccination; secondary: Phagocytic capacity
      of neutrophils; NK-cell activity; Th1 and Th2 cytokine production profiles by PHA stimulated
      PMBCs.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: During the study, 9 blood samples (each 20 or 50 mL) will be taken. Total time
      investment for the subjects will be 160 min. Occasionally, a heamatoma or bruise can occur
      during venipuncture. After the vaccination a heamatoma or a sore arm can occur. These side
      effects should disappear within 4-5 days. Other common side effects related to the
      vaccination are headache, loss of appetite, and fatigue, which usually will disappear within
      24 hours.

      The results of this study will show whether consumption of plant stanol enriched yogurts is
      able to restore the disturbed th1/Th2 balance in asthma patients. Ultimately, this is
      expected to reduce asthmatic exacerbations, as the Th2 dominant immune response seems causal
      to asthmatic symptoms, however these clinical improvements are not verified in this
      relatively short term intervention study.
    


Intervention name(s): Plant stanol enriched soy-based yoghurt; Soy-based yoghurt without added plant stanols
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Plant stanol enriched soy-based yoghurt; Soy-based yoghurt without added plant stanols
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: asthma; allergy; sitostanol; cytokines; Th1; Treg; antibodies; IgE; vaccination