Hayfever Clinical Trial
Official title:
A Randomized, Double-blind, Placebo-controlled Trial of Lactobacillus Acidophilus L92 on Markers of Allergic Inflammation by Nasal Provocation With Grass Pollen
This is a placebo controlled double-blind single center study initiated and sponsored by
CALPIS, Inc., Japan, and CALPIS U.S.A., Inc., Torrance, CA.
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.
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.
An initial study using a desiccated form in tablets has been performed:
4. Artificial pollen allergy study (2005). Improvement in quality of life was noted.
Product: desiccated bacteria and fillers in tablets. 20 mg, 60 mg and 180 mg were
studied. 180 mg/day was most effective. Unpublished data.
METHODS
PHASE 1
In the first phase, subjects with a history of grass pollinosis, with positive skin tests to
grass, will be studied out of season and will be randomized to placebo and active treatment
for 4 months. Randomization will be based upon a retrospective Rhinitis Quality of Life
Questionnaire regarding their recollection of the worst week of the last pollen season. The
intent is to randomize subjects such that the distribution of those with severe versus mild
allergy symptoms is equal in both groups. The subjects will be evaluated for their nasal
function (patency by acoustic rhinometry) and undergo a nasal provocation test and
collection of nasal secretions at the beginning and end of the study. Blood will be drawn
and skin tests will be performed at the beginning and end of the study.
Primary Objective:
To assess the efficacy of L-92 versus placebo by comparing the change in nasal obstruction
using acoustic rhinometry from the baseline, upon nasal provocation with the same dose of
grass pollen extract found to elicit obstruction at enrollment.
Secondary objectives:
1. To compare the change in threshold dose for nasal specific provocation (NPT) test with
grass pollen required to elicit nasal obstruction.
2. To compare the change of serum IgE levels to grass pollen (performed by PHADIA
ImmunoCAP) and total IgE.
3. To compare the change of cytokines IFN-gamma, IL-2, IL-4, IL-5, IL-9 and IL-13, and the
chemokine, eotaxin, in nasal secretion fluid using the same dose of pollen that
elicited nasal obstruction at baseline.
4. To compare the change of cytokines IFN-gamma, IL-2, IL-4, IL-5, IL-9 and IL-13 in the
supernatant from peripheral blood mononuclear cells (PBMCs) stimulated with PHA pre and
post-treatment.
PHASE 2
In the second phase:
Subjects will be given the option to participate for Phase 2 of the study. In this phase,
subjects will continue on either placebo or active product throughout the next pollen
season, starting in January 2008, and fill out Rhinitis Quality of Life Questionnaires when
they pick up the study tablets at the beginning of April, May and June. They will be asked
to fill out daily medication/symptom diaries during the first two weeks of May (exact dates
subject to change depending on climatic factors). The peak grass pollen season is April
through June. Blood will be drawn at a last visit in late June 2008 for specific and total
IgE by ImmunoCAP.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00232518 -
Randomised Controlled Clinical Trials of the Effect of Therapeutic Hookworm Infection in Allergic Rhinoconjunctivitis
|
N/A | |
| Completed |
NCT03755557 -
Demonstration of Equivalence and Early Onset of a Novel Anti-allergic Nasal Spray Compared to Marketed Nasal Spray
|
Phase 3 | |
| Completed |
NCT00854360 -
Study to Assess the Efficacy and Safety of BDP HFA Nasal Aerosol in Patients 12 Years and Older With SAR
|
Phase 2 | |
| Completed |
NCT00150514 -
Effects of Sublingual Immunotherapy on Grasspollen Allergy
|
Phase 4 | |
| Completed |
NCT00290368 -
Repeat Nasal Allergen Challenge
|
Phase 2 | |
| Completed |
NCT00115622 -
Study In Adults And Adolescents With Seasonal Allergic Rhinitis
|
Phase 3 |