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Trial record 1 of 1 for:    Food Allergy Research and Education (FARE)
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FARE Peanut SLIT and Early Tolerance Induction (FARE/SLIT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Food Allergy Research and Education (FARE)
National Center for Complementary and Integrative Health (NCCIH)
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02304991
First received: November 21, 2014
Last updated: July 24, 2017
Last verified: July 2017
  Purpose

Primary Objective: To determine if 36 months of peanut SLIT as an early intervention in subjects ages 1 to 4 years induces clinical desensitization. The primary outcome of this objective will be a statistically significant difference in challenge scores between the treatment group versus the placebo group during DBPCFC (Double blind placebo controlled food challenge) performed after 36 months of peanut SLIT (desensitization). A secondary outcome of this objective will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance). Challenge scores are measured by the amount of peanut protein participants are able to ingest successfully without symptoms of an allergic reaction. [Time Frame: Baseline, 39 months]

Secondary Objective: To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein: 1) peanut specific IgE, IgG, and IgG4 response, 2) peanut specific basophil activation, 3) mast cell responses through skin prick testing, and 4) specific T-cell cytokine responses and T regulatory cell (TReg) activation. The investigators anticipate that the effect of peanut SLIT will occur by induction of TRegs, conversion of T cells from an allergic (TH2) to a non-allergic (TH1) lymphocyte response (measured by cytokines, antibody levels, and skin prick test size), a change in peanut-specific basophil activation, or through a combination of the above.

[Time Frame: Baseline, 39 months]


Condition Intervention Phase
Peanut Hypersensitivity Food Allergy Food Hypersensitivity Peanut Allergy Drug: Liquid Peanut Extract Drug: Placebo Glycerin SLIT Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Peanut Sublingual Immunotherapy Induction of Clinical Tolerance of Newly Diagnosed Peanut Allergic 12 to 48 Month Old Children

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Percentage of participants desensitized to peanut using peanut SLIT as an early intervention in subjects ages 1 to 4 years [ Time Frame: From baseline to 36 months ]
    The primary outcome is to detect a statistically significant difference in reaction thresholds to peanut between the treatment group versus the placebo group during DBPCFC (Double blind placebo controlled food challenge) performed after 36 months of peanut SLIT (desensitization). A secondary outcome of this objective is to detect a statistically significant difference between reaction thresholds to peanut of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance). Challenge scores are measured by the amount of peanut protein participants are able to ingest successfully without symptoms of an allergic reaction. The difference is measured through utilization of an extreme value hazard function.


Secondary Outcome Measures:
  • The change in peanut specific IgE levels [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

  • The change in peanut specific IgG levels [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

  • The change in peanut specific IgG4 levels [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

  • The change in peanut specific basophil activation [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

  • The change in responses of mast cell as measured by prick skin testing to peanut [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

  • The change in specific T-cell cytokine responses [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.

  • The change in T regulatory cell activation [ Time Frame: From baseline to 36 months ]
    To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein. Detection of statistically significant differences will be measured through a two-sample t-test.


Enrollment: 50
Actual Study Start Date: January 2015
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peanut (liquid peanut extract) SLIT
After the entry DBPCFC, subjects will be randomized 1:1 to active or placebo drug product. Subjects randomized to peanut SLIT therapy will dose for 36 months and undergo a second DBPCFC. The subjects will stop dosing for three months and repeat a DBPCFC at 39 months.
Drug: Liquid Peanut Extract
5000mcg/ml peanut protein
Other Name: SLIT
Placebo Comparator: Placebo Glycerin SLIT
After the entry DBPCFC, subjects will be randomized 1:1 to active or placebo drug product. Subjects randomized to placebo glycerin SLIT will dose for 36 months and undergo a second DBPCFC. The subjects will stop dosing for three months and repeat a DBPCFC at 39 months.
Drug: Placebo Glycerin SLIT
pure glycerinated saline solution with caramel coloring to match color
Other Name: SLIT

Detailed Description:

Peanut allergy is one of the most common food allergies; most children develop this allergy early in life, do not outgrow it and are at risk for severe and life-ending anaphylactic reactions. There is a critical need for a proactive treatment for peanut allergy and the investigators along with others are developing specific types of immunotherapy that will act as disease-modifying therapies.

This SLIT study is a randomized, blinded, placebo-controlled study. The primary outcome of this objective will be a statistically significant difference in challenge scores between the treatment group versus the placebo group during DBPCFC performed after 36 months of peanut SLIT (desensitization). A secondary outcome of this objective will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance).

Upon enrollment into the study, all subjects will undergo a qualifying entry DBPCFC with peanut protein to confirm the diagnosis of peanut allergy and establish a baseline threshold level. Following a positive DBPCFC, each subject will be randomized 1:1 to receive peanut SLIT therapy versus placebo for a duration of 36 months. DBPCFC will be repeated for both active and placebo subjects at 36 months to assess desensitization and at 39 months to assess tolerance.

Outcome variables of interest include peanut specific IgE, IgG, and IgG4, basophil activation, mast cell responses through skin prick testing, and specific T-cell cytokine responses and T regulatory cell (TReg) activation.

  Eligibility

Ages Eligible for Study:   12 Months to 48 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent from participant's parent/guardian.
  • Age 12-48 months of either sex, any race, any ethnicity.
  • A peanut allergy diagnosis with a convincing clinical history of peanut allergy and a serum peanut-specific IgE [UniCAP] > 0.35 kUA/L AND a positive skin prick test to peanut (>3 mm than the negative control) OR are sensitized to peanut (based on a serum IgE [UniCAP] to peanut of > 5 kUA/L) AND a positive skin prick test to peanut (> 3 mm than the negative control) and no known history of ingestion of peanut.
  • A positive DBPCFC to 1000 mg of peanut at enrollment.

Exclusion Criteria:

  • History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or neurologic compromise (cyanosis or SpO2 < 92% at any stage, hypotension, confusion, collapse or loss of consciousness).
  • Participation in any interventional study for the treatment of food allergy in the past 6 months.
  • Known oat, wheat, or glycerin allergy.
  • Eosinophilic or other inflammatory (e.g. celiac) gastrointestinal disease.
  • Severe asthma (2007 NHLBI Criteria Steps 5 or 6 - Appendix 2).
  • Inability to discontinue antihistamines for skin testing and DBPCFCs.
  • Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year.
  • Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers.
  • Significant medical condition (e.g., liver, kidney, gastrointestinal, cardiovascular, hematologic, or pulmonary disease) which would make the subject unsuitable for induction of food reactions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02304991

Locations
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Food Allergy Research and Education (FARE)
National Center for Complementary and Integrative Health (NCCIH)
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Wesley Burks, MD University of North Carolina, Chapel Hill
  More Information

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02304991     History of Changes
Other Study ID Numbers: 14-0648
R01AT004435-07 ( U.S. NIH Grant/Contract )
Study First Received: November 21, 2014
Last Updated: July 24, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of North Carolina, Chapel Hill:
Peanut
Food Allergy

Additional relevant MeSH terms:
Hypersensitivity
Food Hypersensitivity
Peanut Hypersensitivity
Immune System Diseases
Hypersensitivity, Immediate
Glycerol
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2017