Oral Peanut Immunotherapy (PNOIT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Wayne G. Shreffler MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01324401
First received: August 12, 2010
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

Peanut allergy is one of the most serious food allergies because of its life long persistence, and the potential for severe allergic reactions. Effective oral immunotherapy would benefit patients by reducing the likelihood that they will have life-threatening accidental allergic reactions. This research study is being done to develop an effective oral immunotherapy treatment for patients with peanut allergy.


Condition Intervention
Peanut Allergy
Drug: Peanut flour OIT

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Oral Peanut Immunotherapy

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 32
Study Start Date: March 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

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:

  1. Induce desensitization in peanut allergic subjects with peanut OIT and evaluate the safety of the peanut OIT desensitization protocol.
  2. Induce long-standing tolerance in peanut allergic subjects with maintenance peanut OIT and evaluate the efficacy of allergen-specific testing to predict tolerance.
  3. Longitudinally evaluate basophil and mast cell reactivity in subjects receiving peanut OIT and their relationship to the induction of desensitization.
  4. Longitudinally evaluate the allergen-specific B-cell repertoire in subjects receiving peanut OIT and its relationship to the induction of tolerance.
  Eligibility

Ages Eligible for Study:   7 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of peanut allergy by a positive prick skin test to peanut (> 8 mm reaction wheal) or CAP FEIA >10 and a history of objective clinical symptoms within one hour after ingestion of peanuts
  2. Ability to provide informed consent.
  3. Males and females of all ethnic/racial groups between 7 and 21 years who are otherwise healthy.

Exclusion criteria:

  1. Clinical history of a severe anaphylactic reaction known or suspected to be caused by ingestion of peanut that required treatment with 2 or more administrations of epinephrine or hospitalization
  2. Moderate to Severe Asthma as defined using the Impairment or Risk Criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/)
  3. Poorly controlled Asthma as defined using the Control Criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/)
  4. Diagnosis of other severe or complicating medical problems
  5. Autoimmune or chronic immune or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders
  6. Primary Immune Deficiency
  7. Use of beta blockers, angiotension converting enzyme inhibitors, or monoamine oxidase inhibitors
  8. Women of childbearing potential who are pregnant, planning to become pregnant, or breastfeeding
  9. Use within the past year of other systemic immunomodulatory treatment, including allergen immunotherapy, use of biologics with an immune target, including Xolair
  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: NCT01324401

Locations
United States, Massachusetts
Food Allergy Center; Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Wayne G Shreffler, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Wayne G. Shreffler MD, Principal Investigator, Center for Immunology and Inflammatory Diseases; Director, Food Allergy Center, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01324401     History of Changes
Other Study ID Numbers: 2010P000609
Study First Received: August 12, 2010
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Peanut Allergy
Peanut Hypersensitivity

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

ClinicalTrials.gov processed this record on July 31, 2014