Five CTSAs Enable NIH-Funded Research on Innovative Allergy Therapy

Peanuts are one of the most common and deadly food allergies, affecting about three in every 500 people across the nation and causing more than half of all deaths from food-related allergic reactions. Finding a new way to treat and possibly prevent the severest of these reactions — and those related to a number of other common foods — could improve the lives of millions. Scientists have discovered a new way of treating food allergy by placing a small amount of the allergen in liquid form under the tongue. Already widely used and approved in Europe to treat environmental allergies, this method, called sublingual immunotherapy, shows real potential for therapeutic development in the United States. But much work remains before that goal can be achieved, including testing the therapy in people.

A record of successful clinical trials makes innovative treatment methods like this one more attractive to pharmaceutical companies, which can develop the therapy into a product for delivery to patients. By sharing part of the risk involved in developing and testing new interventions, especially those to treat life-threatening conditions, NCATS aims to "de-risk" innovative approaches and methods, enabling more efficient translation of basic scientific knowledge into useful treatments.

In the case of peanut allergy, a consortium of scientists at five institutions that receive NIH funding — including through NCATS' Clinical and Translational Science Awards (CTSA) program — took up the challenge of finding a viable treatment approach. Led by Hugh A. Sampson, M.D., director of the Institutes for Translational Sciences at Mount Sinai Hospital's Icahn School of Medicine in New York City, the consortium is working with CTSA program experts in multisite clinical trials to build evidence for sublingual immunotherapy as an effective and much needed treatment.

Food allergies can be dangerous and sometimes lead to death. Even accidental exposure to tiny trace amounts of peanut allergen may cause severe reactions. Of the more than 3 million Americans with peanut or tree nut allergies, only about 20 percent will "outgrow" them and spontaneously stop reacting. Because no treatment is available, Sampson explained, "All we can do is tell them to avoid exposure to foods that trigger the reaction and treat any resulting symptoms."

Collaborations to Improve Translational Research

For nearly a decade, a group of food allergy experts supported by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) has worked to make life safer for people who suffer from food allergies. Known as the Consortium of Food Allergy Research (CoFAR), the group uses NCATS-supported CTSA program resources to conduct clinical trials.

"The CTSA program supports a collaborative interaction that makes studies of this kind possible," said Marshall Plaut, M.D., CoFAR scientific and medical officer and chief of NIAID’s Food Allergy, Atopic Dermatitis and Allergic Mechanisms Section. "The dedicated clinical resources provided by the CTSA sites make it feasible for studies like ours to advance, reducing the difficulties and delays common to multisite trials." The CTSAs also accelerated the research by speeding institutional review board approval, according to David M. Fleischer, M.D., co-leader of the peanut allergy study and associate professor in the Department of Pediatrics at National Jewish Health, a member of the University of Colorado Denver CTSA. "They helped us with the budget and with the protocol submission," he said.

Hugh Sampson, M.D. (left), Steven Woo (center) and Wayne Shreffler, M.D., Ph.D.

Hugh Sampson, M.D. (left), dean for translational biomedical research and the Kurt Hirschhorn Professor of Pediatrics at Mount Sinai School of Medicine, discusses the results of an experiment investigating the cellular mechanisms of peanut allergy with Steven Woo (center), a student, and Wayne Shreffler, M.D., Ph.D. (right), former assistant professor of pediatrics at Mount Sinai School of Medicine. (Matthew Septimus Photo)

CoFAR’s work is a textbook example of how CTSA-provided expertise helps investigators conduct complex, multisite clinical trials. To determine if a therapy is effective, all sites must carry out the study protocol to the letter. That requires each site to have a well-trained staff of research coordinators, nurses and — in a food allergy trial — dietitians to direct food preparation. Considering the real potential for a severe, even deadly reaction to the peanut allergen, the research staff also must understand patients’ needs and be prepared for emergency intervention. Such research, in other words, is time and labor intensive, and the staff must be highly skilled. The food allergen is taken every day, so the risk is always present. "In this trial, the CTSAs provided nursing staff, food preparation, equipment and medications, across all sites," Sampson said.

To help overcome the obstacles often encountered in translational research, about 60 CTSA-funded medical research institutions across the country work together to address translational science problems that no one organization can solve alone. In addition to Mount Sinai Hospital and National Jewish Health, three other CTSA-funded sites participated in this trial: Johns Hopkins Institute for Clinical and Translational Research, Baltimore; the Translational Research Institute at the University of Arkansas for Medical Sciences, Little Rock; and the North Carolina Translational & Clinical Sciences Institute at the University of North Carolina at Chapel Hill.

Testing a New Treatment for Peanut Allergy

CoFAR broke new ground with its publication of the first multicenter, randomized clinical test of sublingual immunotherapy for peanut allergy in the Journal of Allergy and Clinical Immunology in January 2013.

The consortium also has studied oral immunotherapy — in which patients swallow small quantities of the food that causes an allergic response — as a treatment for food allergies. "The sublingual therapy has fewer side effects," Fleischer explained. "It uses a much smaller dose, so it is safer for peanut allergy. What we don’t know is if sublingual immunotherapy will be as effective."

The researchers studied sublingual therapy in 40 people with peanut allergies, divided randomly into two groups. One group of participants received tiny amounts of diluted peanut protein daily, placed under the tongue, and the other group received a placebo. After 44 weeks, 14 of 20 of the people in the group receiving the peanut preparation could tolerate more than 10 times as much peanut powder as they could at the beginning of the study. In other words, many became partially desensitized to peanuts, although this does not necessarily mean they can safely eat them. Even though the results are promising, the amounts of peanut that the subjects can eat currently may not fully protect them from allergic reactions. Further results will determine whether longer duration of therapy will fully desensitize.

"Parents of a child with a peanut allergy — or any food allergy — may be happy just to have the child desensitized so they don’t have to worry about accidental exposure," Fleischer explained. Because avoiding trace amounts of peanuts is quite difficult, even a small level of desensitization could make life much easier for those who do not outgrow the allergy.

Sampson added that CoFAR members explore all aspects of food allergy. The research team continues to collect data from this trial and is recruiting participants for two new trials that will test other therapies. He is excited about the results of the trial so far. "We think this technique can be applied in the United States to other food allergies," Sampson said. "The CTSA provided clinical trial expertise and resources have been critical to our ability to speed this work and get these trials under way, for the benefit of patients."

November 2016 Update: Promising Results for New Peanut Allergy Therapy

In October 2016, CoFAR members published one-year outcomes from an ongoing clinical trial testing a new peanut allergy treatment called epicutaneous immunotherapy (EPIT). The therapy is delivered via a wearable patch that transfers small amounts of peanut protein through the skin. The patch shows promise for treating children and young adults with peanut allergy, with greater benefits for younger children. EPIT was shown to be safe and well tolerated, and nearly all participants used the skin patch daily as directed.

“The high adherence to the daily peanut patch regimen suggests that the patch is easy to use, convenient and safe,” Plaut said. “The results of this study support further investigation of epicutaneous immunotherapy as a novel approach for peanut allergy treatment.”

The CoFAR study team continues to assess the long-term safety and effectiveness of EPIT. The one-year outcomes were published online on Oct. 26, 2016, in the Journal of Allergy and Clinical Immunology.

Posted October 2013