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Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance (SLIT-TLC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Wesley Burks, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01373242
First received: June 12, 2011
Last updated: October 24, 2016
Last verified: October 2016
  Purpose
The goal of this study will be to increase the reaction threshold (desensitization) of peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance).

Condition Intervention Phase
Peanut Hypersensitivity
Food Hypersensitivity
Food Allergy
Peanut Allergy
Drug: Liquid peanut extract (Peanut SLIT)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Peanut Sublingual Immunotherapy and Induction of Clinical Tolerance in Peanut Allergic Children (SLIT Tolerance TLC) {Sublingual Immunotherapy for Peanut Allergy}

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of subjects on peanut SLIT who pass the final double blind, placebo controlled food challenge to assess tolerance after the randomized tolerance period. [ Time Frame: 48 - 52 months ] [ Designated as safety issue: Yes ]
    Subjects are treated for at least 48 months and then given a randomized tolerance period of 1-17 weeks prior to a final DBPCFC to assess tolerance.


Secondary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 [ Time Frame: 52 months ] [ Designated as safety issue: Yes ]
  • Change from baseline in peanut skin prick testing at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in peanut basophil activation at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in peanut-specific IgE at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in peanut-specific IgG4 at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in peanut-specific IgA at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in TH1 cytokine levels (IFN-gamma, TNF-alpha) at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in TH2 cytokine levels (IL-4, IL-5, IL-13, IL-10) at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in regulatory T-cell cytokines (IL-10, TGF-beta) at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Change from baseline in regulatory T-cells at 48 months and at the final avoidance DBPCFC. [ Time Frame: 52 months ] [ Designated as safety issue: No ]
  • Correlation of baseline subject characteristics (age, race, sex, weight, height, baseline peanut skin test, baseline peanut IgE) with successful desensitization as well as with the maintenance of desensitization after treatment avoidance. [ Time Frame: 52 months ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: June 2011
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peanut ( liquid peanut extract) SLIT
All subjects will receive peanut SLIT upon enrollment for at least the first 48 months. After the desensitization DBPCFC after at least 48 months of treatment, subjects will be randomized off treatment from 1 to 17 weeks. Subjects will then undergo another DBPCFC.
Drug: Liquid peanut extract (Peanut SLIT)
Liquid peanut extract will be administered under the tongue
Other Name: Peanut SLIT - active arm

Detailed Description:

Allergy to peanuts and tree nuts affects approximately 1.4% of the population. Allergic reactions to peanut can be severe and life threatening and account for the vast majority of fatalities due to food-induced anaphylaxis. At present, there are no viable treatment options for patients with peanut allergy. The current standard of care is strict dietary elimination and emergency preparedness with an anaphylaxis kit in the event of an accidental reaction.

Our group and others have shown that oral immunotherapy can provide protection from anaphylaxis to a variety of food proteins. In addition, our ongoing research has demonstrated that sublingual immunotherapy to peanut provides a safe, alternative mode of immunotherapy to reduce allergic reaction rates (desensitization) during oral food challenge (OFC) to peanut. The goal of this study will be to desensitize peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance). Children ages 1-11 years will be enrolled following an entry double blind, placebo controlled food challenge (DBPCFC).

After at least 48 months of peanut SLIT study drug, subjects will undergo a second DBPCFC to 5000 mg of peanut protein to assess desensitization.

  • Subjects who are not desensitized are those who are not able to consume more than the MCRT without symptoms, which has been defined as 300 mg of peanut protein. Subjects who consume less than 300 mg of peanut protein without symptoms will stop peanut SLIT and conclude the study. These subjects will not undergo any additional study procedures including the remaining protocol DBPCFCs and will be recommended to resume a strict peanut avoidance diet.
  • Subjects who are able to consume more than 300 mg of peanut protein will be randomized to an interval between 1 and 17 weeks during which all peanut including peanut SLIT study drug will be discontinued. This period of avoidance will be followed by a third DBPCFC to 5000 mg of peanut protein to evaluate for the loss of the desensitization effect. After this final DBPCFC, the study will be completed for these subjects. At the primary investigators clinical discretion, they will be recommended to transition to a daily peanut food equivalent to maintain the desensitized effect.

Outcome variables of interest include response to double blind, placebo controlled food challenges, skin prick testing, peanut specific serum immunoglobin E (IgE), immunoglobin G (IgG), and immunoglobin G4 (IgG4) and salivary immunoglobin A (IgA), T and B cell responses, basophil hyporesponsiveness, quality of life, and adverse events.

  Eligibility

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

Inclusion Criteria:

  • Age 1-11 years
  • Peanut specific IgE > 0.35kU/L or a convincing clinical history of an allergic reaction to peanut within 1 hour of ingestion
  • Positive entry DBPCFC to 1 gram of peanut protein

Exclusion Criteria:

  • History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or neurologic compromise (cyanosis or oxygen saturations < 92% at any stage, hypotension, confusion, collapse, loss of consciousness, or incontinence)
  • 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 National Heart Lung and Blood Institute (NHLBI) guidelines 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: NCT01373242

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
National Center for Complementary and Integrative Health (NCCIH)
Investigators
Principal Investigator: Wesley Burks, MD University of North Carolina
  More Information

Responsible Party: Wesley Burks, MD, Executive Dean, School of Medicine, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01373242     History of Changes
Other Study ID Numbers: 11-2308  5R01AT004435-09 
Study First Received: June 12, 2011
Last Updated: October 24, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Hypersensitivity
Food Hypersensitivity
Peanut Hypersensitivity
Immune System Diseases
Hypersensitivity, Immediate

ClinicalTrials.gov processed this record on December 08, 2016