A Randomized, Double-blind, Placebo-controlled Trial of Lactobacillus Acidophilus L92 on Markers of Allergic Inflammation by Nasal Provocation With Grass Pollen

The overall objective of this study is to establish the benefit of a bacterial product, Lactobacillus acidophilus strain L-92 (CALPIS U.S.A., Inc., Torrance, CA), in patients with allergic rhinitis. This will be done by noting:

• The threshold dose of pollen extract required on nasal challenge needed to elicit nasal obstruction as measured by acoustic rhinometry pre-treatment, and then comparing the nasal response to the same dose at the end of treatment.
• The dose of pollen extract needed (by progressive dose escalation) to elicit nasal obstruction at the end of treatment if significant nasal obstruction is not reached with the pre-treatment dose.
• Changes in the cytokine and chemokine profile obtained by analysis of the nasal secretion specimens pre- and post-treatment.
• Changes in the cytokine profile of cultured peripheral blood mononuclear cells stimulated with PHA pre- and post-treatment.
• PHADIA ImmunoCAP perennial ryegrass pollen titer pre- and post-treatment.
• The threshold concentration of standardized perennial ryegrass extract to elicit a positive skin prick test pre- and post-treatment
• Total serum IgE pre- and post-

The active product to be used is a tablet made from desiccated Lactobacillus acidophilus strain L-92 and fillers. These bacteria are present in the GI tract of most healthy humans. They are non-pathogenic, and have been used in the food industry for preparation of fermented foods for centuries. They lower the pH of their environment by converting sugar to lactic acid, which inhibits the growth of some pathogens. Lactobacilli are the first genus of bacteria suspected to have health benefits. Most Probiotic studies have been done with live cultures, and indeed there is animal model literature to support greater beneficial immunomodulatory effects of live bacteria over killed organisms. However, some beneficial effects of Lactobacilli are proposed to be due to uptake and processing of cell wall components and bacterial DNA, thus interaction with living bacteria may not be required for all the beneficial effects. However, if a tablet form can deliver live bacteria, in terms of ease of consumption by consumers, it would be preferred by many people, as well as allowing easier blinding of the supplement in clinical trials. The study proposed herein will be the first large study of this product using a live, but desiccated tablet preparation of the bacteria. If this product has a beneficial effect, the fact that it is in a tablet form will greatly benefit consistency in manufacturing, as well as ease storage and ultimate use of the product by consumers.

CALPIS has selected a strain of lactobacilli, L. acidophilus (L92), on the basis of an IgE- lowering effect in experimental studies with mice. This product, in a liquid fermented milk form, has been tested in the following clinical studies:

1. Cedar pollen allergy study (2003). Significant improvement in symptom-medication score was detected (ISHIDA et al BIOSCI. BIOTECH. BIOCHEM. 1652-60, 2005). Product: Liquid fermentation L acidophilus L-92 milk, heat-treated at 75°C for 10 minutes in 100 mL volume.
2. Perennial allergic rhinitis (2002/03). Significant improvement in symptom-medication score was observed (ISHIDA et al J. Dairy Sci. 528-33, 2005). Product: 100 mL heat-treated milk fermented by L acidophilus L-92 (about 3x1010 counts/100 mL)
3. Atopic dermatitis (2005). Improvement in symptom-medication score was detected. Unpublished data. Product: 100 mL fermented milk with L acidophilus L-92.