Oral Peanut Immunotherapy (PNOIT)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Oral Peanut Immunotherapy|
- Tolerance [ Time Frame: at least 36 months ] [ Designated as safety issue: No ]Tolerance will be defined in this study as a loss of clinical sensitivity to peanut. Subjects will be considered to have achieved tolerance if the post treatment eliciting dose (ED), defined by the double blind placebo controlled food challenge, is five fold increase from the ED of baseline.
- Desensitization [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]A five-fold increase in ED defined by OFC at the conclusion of maintenance therapy
- The frequency of side-effects and their relationship to other variables [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]
- A significantly lower frequency of accidental ingestion reactions compared to controls [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]
- A longitudinal suppression of end-point skin testing by 2 log dilution. [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]
- A longitudinal suppression of peanut-specific basophil activation by 1.5 log dilution [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]
- A longitudinal doubling of peanut-specific IgG4 [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]
- A longitudinal increase of Ara h 2-specific IgG+ B cells by >1.5 SD [ Time Frame: at least 36 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||May 2018|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
No Intervention: Control
The subjects enrolled in the observational control group will have follow-up visits every 6 months. Each visit will involve a medical history and physical examination.
|Experimental: Peanut OIT||
Drug: Peanut flour OIT
Patients will receive daily escalating dosages as determined in the modified rush phase as stated in the protocol. The dosage will be escalated until a daily dose of 4000 mg is reached. A Double-blind, placebo-controlled food challenge will then consist of two challenges performed on the same day. One challenge will consist of 7 doses of peanut given every 10-20 minutes in increasing amounts up to a total of 10 grams of whole peanut (5 grams of peanut protein) masked by inclusion in vehicle food. The other challenge will consist of placebo material given similarly.
Our hypothesis is that chronic antigen exposure during peanut oral immunotherapy (OIT) will induce beneficial changes in the specific immune response, including: 1) anergy of IgE effector immune cells (e.g., mast cells, basophils) resulting in clinical desensitization; 2) induction of de novo, long lived (memory) B cell responses that antagonize specific IgE and confer immune tolerance. The investigators will test this hypothesis in the following specific aims:
- Induce desensitization in peanut allergic subjects with peanut OIT and evaluate the safety of the peanut OIT desensitization protocol.
- Induce long-standing tolerance in peanut allergic subjects with maintenance peanut OIT and evaluate the efficacy of allergen-specific testing to predict tolerance.
- Longitudinally evaluate basophil and mast cell reactivity in subjects receiving peanut OIT and their relationship to the induction of desensitization.
- Longitudinally evaluate the allergen-specific B-cell repertoire in subjects receiving peanut OIT and its relationship to the induction of tolerance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01324401
|United States, Massachusetts|
|Food Allergy Center; Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Wayne G Shreffler, MD, PhD||Massachusetts General Hospital|