Walnut Oral Immunotherapy for Tree Nut Allergy (WOIT)

This study has been withdrawn prior to enrollment.
(Concern for cross contamination in weighing tree nuts in facility with peanuts)
Sponsor:
Information provided by (Responsible Party):
Wesley Burks, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01834352
First received: April 12, 2013
Last updated: March 21, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to determine if walnut oral immunotherapy can be used in subjects allergic to tree nuts to decrease their tree nut allergy and induce changes in their immune system.


Condition Intervention Phase
Nut Hypersensitivities
Drug: Walnut Protein Flour
Drug: Oat flour
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Walnut Oral Immunotherapy for Tree Nut Allergy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Effectiveness of walnut oral immunotherapy (WOIT) on clinical desensitization to a second tree nut. [ Time Frame: 38 weeks ] [ Designated as safety issue: Yes ]
    The determination of the effectiveness of WOIT in inducing clinical desensitization to a second tree nut to which the subject is allergic when compared to placebo. This will be measured by the change in the amount of tree nut the subject can consume during their food challenge at 38 weeks compared to their consumption during the baseline challenge at study entry.


Secondary Outcome Measures:
  • Percentage of subjects who can tolerate a 5000mg oral food challenge to walnut protein following the desensitization phase of the study [ Time Frame: 38 weeks ] [ Designated as safety issue: Yes ]
    The percentage of subjects who can consume all of the 5000mg of walnut protein without symptoms during the food challenge after the desensitization phase of the study.

  • The percentage of subjects who are able to reach a cumulative protein dose of 2000mg at the desensitization oral food challenge to walnut and the test tree nut. [ Time Frame: 38 weeks ] [ Designated as safety issue: Yes ]
    The percentage of subjects who are able to consume a cumulative protein dose of 2000 mg of walnut and test tree nut without symptoms during the desensitization oral food challenge.

  • The percentage of subjects who demonstrate clinical tolerance at the end of the study to walnut and the test tree nut. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    The percentage of subjects who are able to demonstrate clinical tolerance by consuming all of the walnut and test tree nut without symptoms during the oral food challenge at the end of the study.


Other Outcome Measures:
  • Increase in walnut and test tree nut IgG4 over the course of the study. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    The increase in the walnut and test tree nut specific IgG4 over the course of the study as an indication of the impact of WOIT on the immune system.

  • Decrease in the walnut and test tree nut specific IgE over the course of the study. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    The decrease in the walnut and test tree nut specific IgE over the course of the study as an indication of the impact of WOIT on the immune system.


Enrollment: 0
Study Start Date: November 2013
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Walnut protein flour
Walnut protein flour administered in varying dose amounts which begin at a low dose and are increased every 2 weeks until the maximum dose is achieved.
Drug: Walnut Protein Flour
The initial day escalation begins with a dose of 0.1 mg of walnut protein. The dose is then increased and administered every thirty minutes until a maximum dose of 6 mg is reached or until allergic symptoms develop. After the initial escalation day, subjects begin the build-up phase in which the dose is increased every two weeks to a maximum dose of 1500mg walnut protein at 34 weeks. After 34 weeks of build-up, the subject begins the maintenance phase in which daily dose (1500mg or the highest dose reached by 34 weeks) is taken for 4 weeks followed by a 5 gram protein oral food challenge to walnut and a 5 gram protein oral food challenge to the second tree nut (at 38 weeks). Then the study will be unblinded. Active treatment subjects will continue on the 1500mg walnut protein daily dose for a maximum of 33 months.
Placebo Comparator: Oat flour
Oat flour administered in varying dose amounts which begin at a low dose and are increased every 2 weeks until the maximum dose is achieved.
Drug: Oat flour
The initial day escalation begins with a dose of 0.1 mg of oat flour. The dose is then increased and administered every thirty minutes until a maximum dose of 6 mg is reached or until allergic symptoms develop. After the initial escalation day, subjects begin the build-up phase in which the dose is increased every two weeks to a maximum dose of 1500mg oat flour at 34 weeks. After 34 weeks of build-up, the subject begins the maintenance phase in which daily dose (1500mg or the highest dose reached by 34 weeks) is taken for 4 weeks followed by a 5 gram protein oral food challenge to walnut and a 5 gram protein oral food challenge to the second tree nut (at 38 weeks). Then the study will be unblinded. Placebo subjects that fail the OFC will be crossed over to active treatment beginning with the initial escalation day, build-up and maintenance.

Detailed Description:

Tree nut

  Eligibility

Ages Eligible for Study:   6 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 6 to 45 years, either sex, any race, any ethnicity with a convincing clinical history of walnut or another tree nut allergy and either a positive prick skin test (> 3mm) or serologic evidence of allergic sensitization (defined as specific IgE > 0.35 kU/L) to walnut and at least one other tree nut.
  • A positive 2000 mg oral food challenge at enrollment to walnut and to one other tree nut.
  • Written informed consent from participant and/or parent/guardian
  • Written assent from all subjects as appropriate
  • All females of child bearing age must be using appropriate birth control

Exclusion Criteria:

  • History of severe anaphylaxis to walnut or other tree nuts, defined as symptoms associated with hypoxia, hypotension or neurologic compromise (cyanosis or SpO2 < 92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence).
  • Known allergy to oat
  • Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy or other respiratory or medical conditions deemed by the investigator to put the subject at increased risk of anaphylaxis or poor outcomes from receiving OIT or undergoing food challenge.
  • Poor control or persistent activation of atopic dermatitis
  • Active eosinophilic or other inflammatory (e.g., celiac) gastrointestinal disease in the past 2 years.
  • Participation in any interventional study for food allergy in the past 6 months
  • Participant is on "build-up phase" of immunotherapy (i.e., has not reached maintenance dosing).
  • Severe asthma (2007 NHLBI Criteria Steps 5 or 6, see Appendix 2) or poorly controlled mild or moderate asthma
  • Inability to discontinue antihistamines for initial day escalation, skin testing or OFC
  • 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
  • Pregnancy or lactation
  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: NCT01834352

Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Wesley Burks, MD UNC Chapel Hill
Study Chair: Brian Vickery, MD UNC Chapel Hill
Study Director: Edwin Kim, MD UNC Chapel Hill
  More Information

Publications:
Responsible Party: Wesley Burks, MD, Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01834352     History of Changes
Other Study ID Numbers: 13-1289
Study First Received: April 12, 2013
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
Walnut hypersensitivity
Tree nut hypersensitivity

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

ClinicalTrials.gov processed this record on August 19, 2014