The following is a detailed description of the Real World Bio-Marker Study currently open to private funding.

A Real-World Study Pointing the Way Towards Relief from Severe Food Allergies

By Dr. Xiu-Min Li, Dr. Paul Ehrlich, and Dr. Purvi Parikh

Because there has never been an approved cure for food allergies, there has never been an incentive to measure patient progress during therapy. Instead, patients have managed the problem by avoiding the foods and preparing for emergencies while waiting for nature to take its course; either a patient will outgrow an allergy or not. Allergen-specific IgE levels in the blood may rise and fall without predicting the likelihood of a serious allergic reaction. Food challenges are the truest test, but they are not suitable for periodic use, and are so anxiety provoking that many people don’t try them even after their allergist recommends it. If, however, a reasonably expeditious treatment could be found, tools to show “tolerance in a test tube” would be warranted.

That moment is at hand, and is the premise of a new study we are planning to undertake called, “Practice-Based Bio-Marker Study using Traditional Chinese Medicine to Prove Real Life Effects on Patients with Poly-Allergen Sensitization.” The past several years, have seen great progress in treating food allergies with compounds taken from traditional Chinese medicine (TCM), specifically a botanical drug called FAHF-2 (food allergy herbal formula) and now a refined, much-more-potent version called B-FAHF-2.* The results to date are sufficiently encouraging to treat patients in a practice-based study and to see if we can measure progress by examining changes in the blood chemistry. The first cohort of approximately 10 patients who meet study criteria will be treated through our combined efforts.

We will be looking at several bio-markers—chemical indicators that correspond to changes in immune activity. One is basophil activation. Basophils and mast cells are effector cells. They both contain mediators, such as histamines, that are released when they encounter an allergen. Unlike mast cells, which are lodged in tissue, basophils circulate in the blood and are easily extractable with a minimal blood draw. Exposed to antigens in a laboratory, basophils can be activated, producing, in effect, an allergic response at no risk to the patient. Basophil activation tests (BATs) are used in research, but if this treatment becomes more widespread, they may become more common at the practice level.

Another is DNA methylation by the Th1 and Th2 cells. DNA methylation determines “gene expression”—turning on and off cellular secretion of certain cytokines (small proteins that help regulate the immune response). In a healthy immune system, Th1 cells dominate, helping fight infectious disease. In an allergic individual, Th2 cells, which are normally associated with fighting invasive parasites, are too powerful, and they attack proteins in things like pollens and foods. We are going to study two markers: 1) IFN-γ, the principal Th1 effector cytokine, which plays a crucial role in counteracting and suppressing Th2 responses of allergic diseases. It is deficient in food allergic patients. 2) RANTES (CCL5), which is highly secreted in food allergy patients and plays an important role in recruiting basophils, eosinophils, and T cells into the inflammatory sites.

The Protocol

Although oral food challenge is the gold standard for diagnosis of food allergy, patients with a history of severe reactions and high levels of IgE are understandably reluctant to undergo food challenge at baseline. Thus, there will be no initial challenge as there is in some research.

This is a practice-based study. There will be no placebo controls (everyone will receive TCM treatment). However, there will be an observational control group supplied by an in vitro blood sampling of patients with poly-allergen sensitization who have never received TCM or other treatments beyond that of a medically restricted diet. These untreated samples will undergo the same tests of the treated blood for comparison.

If patients’ immunological responses (IgE levels and basophil activation and T cell epigenetic status) are dramatically improved by treatment compared to baseline, and if the family is interested in introducing certain foods, we will determine clinical tolerability. This will be done using standard allergy protocols, or perhaps using newer tools now in development that are considered highly predictive of the results of a food challenge. The goal is, of course, a broader range of nutritious food, consumed without fear of a reaction.

Unlike other studies, in which subjects usually have a narrow set of allergic conditions at baseline, this one is more like the “real world” of food allergic patients. Those with severe food allergies often have other allergic diseases, and they can take part in this research, where in other studies they might be excluded. This study is also suitable for children with multiple food allergies who have histories of severe reactions. It is patient friendly and cost effective. The data will be important for designing a controlled, prospective study and for NIH funding application in the future. If successful, this protocol can be adopted by other allergists in their practices. Also, because TCM is inherently an individualized approach to medicine, other herbal drugs, as well as acupuncture and acupressure, may be used for different patients depending on their other conditions. This will not compromise the integrity of the bio-marker data.

Who Will Be Eligible?

Patients are required to have:

  • A convincing history of anaphylaxis to peanut and tree nut, plus one of the following categories:
  1. Peanut and/or any tree nut, or seeds specific IgE levels >100 KU/L.
  2. IgE levels >15 KU/L that increased over the last two years
  3. Frequent and potentially severe reactions (>1 reaction per month)
  4. Baseline basophil activation > 60% in response to allergen (peanut and/or tree nut) stimulation

Ages 2-16 years will be recruited

Other aspects to be considered:

  • Normal lab data on CBC and Comprehensive metabolic panel; however, distinct from studies of oral immunotherapy for food allergies (OIT) and other experimental treatments, patients with an elevated percent of blood eosinophils will not be excluded. Patients with elevated peripheral percent of blood eosinophils, and significant co-morbidities such as environmental allergies or eczema are typical of Poly-Allergen Sensitization, and cannot be omitted from a real world study.
  • OIT drop out patients, previous TCM, or other alternative-therapy-treated patients are welcome to participate in this study. A percentage of this population has shown reduction of poly-sensitization symptoms. Because they are poly-sensitized with multiple food allergens, some have successfully passed challenges on some of the foods, but not all. Their best hope is to continue on TCM and introduce more foods. By testing for the degree of basophil sensitization and T cell epigenetic changes, we can use their current IgE levels, basophil sensitization, and T cell epigenetic profile and document those changes to provide a baseline for established patients. The improvement of these bio-markers will be a good indication that future TCM patients may be able to tolerate that particular food.
  • Patients with primary eosinophilic esophagitis (i.e. EoE without IgE-mediated food allergies) will not be included in this study since primary EoE patients do not have highly elevated IgE levels and abnormal basophil activation is not a major concern.
  • Patients must agree to follow the current TCM protocol.

TCM therapy
Patients will receive TCM therapy at an off-site TCM clinic (Ming Qi Natural Health Care Center) from Dr. Li. TCM treatment remedies will include internal and external herbal medications based on Dr. Li’s TCM practice. Acupuncture/acupressure treatment will also be included at TCM visits. Allergy services will be provided at Allergy & Asthma Associates of Murray Hill.

B-FAHF-2 will be used as a baseline remedy, as will acupuncture or acupressure, though frequency may vary. An established protocol will also allow for the use the other herbal remedies, depending on the real life conditions. Specifically: There will be remedy A (B-FAHF-2); Remedy B (herbal cream); Remedy C (digestions tea); Remedy D (IgE tea).

*(The story of this research is told in Henry Ehrlich’s book, Food Allergies: Traditional Chinese Medicine, Western Science, and the Search for a Cure.)


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