Clinical trial NCT01373242: Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance
Official title: Peanut Sublingual Immunotherapy and Induction of Clinical Tolerance in Peanut Allergic Children (SLIT Tolerance TLC) {Sublingual Immunotherapy for Peanut Allergy}
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Peanut Hypersensitivity
Food Hypersensitivity
Food Allergy
Peanut Allergy
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2011-06-14
Enrollment: 54
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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 criteria: Inclusion Criteria:

* Between ages 1 year to 12 years exclusive
* 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

Primary outcomes:
measure: Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population
timeFrame: 48 - 52 months
measure: Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population
timeFrame: 48-52 months
measure: Population Estimate of Time for a Subject's True Sensitivity Threshold to Reduce by Half.
timeFrame: 52 months
measure: Population Estimate of a Subject's True Sensitivity Threshold to Maintain at the Same Dose Level During DBPCFC
timeFrame: 52 months
measure: Population Estimate of a Subject's True Sensitivity Threshold to Decrease by One Dose Level of During the DBPCFC
timeFrame: 52 months
Secondary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events During the Study.
timeFrame: 48 months
measure: Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events.
timeFrame: 48 months
measure: Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
timeFrame: 48 months
measure: Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
timeFrame: 48 months
measure: Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
timeFrame: 48 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Wesley Burks, MD
role: PRINCIPAL_INVESTIGATOR
References: