A Study of Sublingual Immunotherapy in Peanut-allergic Children (SLB)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Wesley Burks, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00597727
First received: January 7, 2008
Last updated: October 10, 2015
Last verified: October 2015
  Purpose
The specific aim of this study is to determine if peanut allergen-specific SLIT will cause clinical desensitization and tolerance to develop in peanut-allergic young children.

Condition Intervention
Food Hypersensitivity
Drug: Peanut SLIT
Drug: Placebo SLIT

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blinded, Placebo-controlled Study of Peanut Sublingual Immunotherapy in Children - DBPC Peanut SLIT

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determine if peanut-specific SLIT will cause clinical desensitization to develop in peanut-allergic young children. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine the percentage of subjects who can tolerate the 5 gram peanut challenge after undergoing the 12 month peanut SLIT desensitization portion of the protocol.


Secondary Outcome Measures:
  • Determine if peanut-specific SLIT will cause tolerance to develop in peanut-allergic young children. [ Time Frame: baseline and at least annually up to 68 months ] [ Designated as safety issue: Yes ]
    To determine the percentage of subjects who can tolerate 10 grams of peanut flour, 2 - 4 weeks after discontinuing peanut SLIT.

  • Determine if the development of the desensitized state and tolerance to peanut is associated with the down-regulation of mast cells and basophils. [ Time Frame: baseline and at least annually up to 68 months ] [ Designated as safety issue: No ]
    To determine the percentage of CD63+ basophils at baseline and throughout the study.

  • Determine the effect of peanut-specific mucosal and systemic humoral immune responses on oral tolerance and peanut SLIT. [ Time Frame: baseline and at least annually up to 68 months ] [ Designated as safety issue: No ]
    Determine the allergen-specific endpoint titer for each antibody class of interest (serum IgA, IgG, IgG4, IgE, IgM; also salivary IgA) at baseline and throughout the study.

  • Delineate the mechanism of the T-cell response to allergen-specific T-cells during peanut SLIT - (regulatory T cells). [ Time Frame: baseline and at least annually up to 68 months ] [ Designated as safety issue: No ]
    Determine the change in T-reg gene expression of peanut antigen-stimulated T-cells at baseline and throughout the study.

  • Delineate the mechanism of the T-cell response to allergen-specific T-cells during peanut SLIT - (TH2/TH1 cytokines). [ Time Frame: baseline and at least annually up to 68 months ] [ Designated as safety issue: No ]
    Determine if the persistence of clinical peanut allergy is associated with the maintenance of a peanut-specific, Th2-skewed T-cell phenotype vs a Th1-skewed phenotype by measuring IL-4, IL-10, and IL-13 expression by quantitative real time PCR and by ELISA and GATA-3 and T-bet expression as measured by quantitative real time PCR.

  • Delineate the mechanism of the T-cell response to allergen-specific T-cells during peanut SLIT - (oligonucleotide microarrays). [ Time Frame: baseline and at least annually up to 68 months ] [ Designated as safety issue: No ]
    Determine if changes in T-cell transcription patterns reflect postulated decreased Th2 responses in subjects who have undergone successful peanut SLIT (developed clinical tolerance).


Enrollment: 33
Study Start Date: January 2008
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Peanut SLIT
Subjects who receive the protein (peanut sublingual drops) at the beginning of the study.
Drug: Peanut SLIT
Liquid peanut protein drops diluted in glycerin which are dosed under the tongue.
Other Name: Sublingual peanut protein drops
Placebo Comparator: Placebo SLIT
Subjects who receive placebo (glycerin sublingual drops) at the beginning of the study.
Drug: Placebo SLIT
Liquid glycerin without peanut which are dosed under the tongue.
Other Name: Sublingual glycerin saline drops

Detailed Description:

In spite of increased recognition and understanding of food allergies, food-induced anaphylaxis remains the single most common cause of anaphylaxis seen in hospital emergency departments, accounting for about one third of anaphylaxis cases seen. It is estimated that about 30,000 food-induced anaphylactic events are seen in U.S. emergency departments each year and that about 200 fatal cases occur in the U.S. each year. Either peanuts or tree nuts cause more than 80% of these reactions. No treatments are available and avoidance is the only approved intervention.

The goal of this study is to investigate peanut sublingual immunotherapy (SLIT) as a treatment for children with peanut allergy. This study is designed to evaluate the efficacy and safety of peanut SLIT compared to placebo after 12 months. Mechanistic studies will be completed concurrently to understand changes in the allergic immune response related to peanut SLIT. The remainder of the study is designed to evaluate the efficacy of peanut SLIT in inducing lasting tolerance after discontinuation of the peanut SLIT.

  Eligibility

Ages Eligible for Study:   1 Year to 11 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Peanut IgE > 7kU/L (> 2kU/L for children aged 2 years and under) AND
  • History of significant clinical symptoms within 60 minutes after the ingestion of peanuts.

Exclusion Criteria:

  • History of severe life-threatening anaphylaxis to peanut, OR
  • Medical history that would prevent a DBPCFC to peanut, OR
  • Subjects with wheat or oat allergy (which are used in the placebo), OR
  • Unable to cooperate with challenge procedures, OR
  • Unable to be reached by telephone for follow-up
  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: NCT00597727

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Wesley Burks, MD University of North Carolina
  More Information

Publications:
Responsible Party: Wesley Burks, MD, Chairman, Department of Pediatrics, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00597727     History of Changes
Other Study ID Numbers: 11-2296 
Study First Received: January 7, 2008
Last Updated: October 10, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 25, 2016