Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance (SLIT2)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
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: March 21, 2014
Last verified: March 2014
  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)
Drug: Placebo Glycerin SLIT
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Peanut Sublingual Immunotherapy and Induction of Clinical Tolerance in Peanut Allergic Children

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of subjects on placebo vs peanut SLIT who pass the 54 month double blind, placebo controlled food challenge to assess tolerance. [ Time Frame: 54 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of subjects who demonstrate clinical desensitization by passing the 48 month double-blind, placebo-controlled food challenge. [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Induction of clinical tolerance after 48months vs 60 months of peanut SLIT. [ Time Frame: 66 months ] [ Designated as safety issue: Yes ]
  • The change in immune parameters over time associated with the induction of tolerance. [ Time Frame: 66 months ] [ Designated as safety issue: No ]
  • The change of immune function of those who achieve tolerance versus those who do not achieve tolerance. [ Time Frame: 66 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2011
Estimated Study Completion Date: June 2021
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 the first 48 months. After the desensitization DBPCFC at 48 months, subjects will be randomized 2:1 to placebo or continued peanut SLIT. The SLIT group will complete 60 months of SLIT prior to undergoing a final DBPCFC at 66 months to assess clinical tolerance.
Drug: Liquid peanut extract (Peanut SLIT)
Liquid peanut extract will be administered under the tongue
Other Name: Peanut SLIT - active arm
Placebo Comparator: Placebo Glycerin SLIT
All subjects will receive peanut SLIT for 48 months upon enrollment. After the desensitization DBPCFC at 48 months, subjects will be randomized 2:1 to placebo or continued peanut SLIT for 6 months and then undergo a DBPCFC to assess clinical tolerance. The placebo subjects will either demonstrate tolerance or be eligible to restart SLIT for the remainder of the study if they fail to achieve tolerance.
Drug: Placebo Glycerin SLIT
Liquid glycerin extract will be administered under the tongue
Other Name: Placebo Glycerin SLIT

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). All children will receive peanut sublingual immunotherapy (SLIT) for 48 months and before undergoing a second DBPCFC. Subjects who demonstrate desensitization at this food challenge will be randomized to placebo or continued peanut SLIT for 6 months prior to undergoing a third DBPCFC to assess clinical tolerance. Subjects randomized to continued peanut SLIT will complete 6 additional months of the study drug. At that point, they will discontinue SLIT for 6 months and have a final DBPCFC to assess tolerance at the end of study (66 months). 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
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
Investigators
Principal Investigator: Wesley Burks, MD University of North Carolina
  More Information

No publications provided

Responsible Party: Wesley Burks, MD, Chairman, Department of Pediatrics, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01373242     History of Changes
Other Study ID Numbers: 00029390, 1R01AT004435-01
Study First Received: June 12, 2011
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on July 31, 2014