Walnut Oral Immunotherapy for Tree Nut Allergy (WOIT)

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.

Study Overview

• Status: Withdrawn
• Conditions: Nut Hypersensitivities
• Intervention / Treatment: Drug: Walnut Protein Flour; Drug: Oat flour

Detailed Description

Tree nut

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Walnut protein flour; Walnut protein flour that is ingested in gradually increasing amounts up to a maintenance dose.	Drug: Walnut Protein Flour; Daily ingestion of gradually increasing amounts of walnut protein flour in order to induce desensitization to walnut and an unrelated tree nut.; Other Names: Walnut OIT
Placebo Comparator: Oat flour; Oat flour administered in identical increasing amounts as the active walnut protein flour.	Drug: Oat flour; Oat flour that is administered as a placebo in identical increasing doses as the active walnut flour treatment.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of walnut oral immunotherapy (WOIT) on clinical desensitization to a second tree nut.	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.	38 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects who can tolerate a 5000mg oral food challenge to walnut protein following the desensitization phase of the study	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.	38 weeks
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.	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.	38 weeks
The percentage of subjects who demonstrate clinical tolerance at the end of the study to walnut and the test tree nut.	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.	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in walnut and test tree nut IgG4 over the course of the study.	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.	36 months
Decrease in the walnut and test tree nut specific IgE over the course of the study.	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.	36 months

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Wesley Burks, MD, UNC Chapel Hill; Study Director: Edwin Kim, MD, UNC Chapel Hill

Publications and helpful links

General Publications

• Kulis M, Li Y, Lane H, Pons L, Burks W. Single-tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts. J Allergy Clin Immunol. 2011 Jan;127(1):81-8. doi: 10.1016/j.jaci.2010.09.014. Epub 2010 Nov 18.
• Hofmann AM, Scurlock AM, Jones SM, Palmer KP, Lokhnygina Y, Steele PH, Kamilaris J, Burks AW. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol. 2009 Aug;124(2):286-91, 291.e1-6. doi: 10.1016/j.jaci.2009.03.045. Epub 2009 May 27.
• Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M, Francis JM, Durham S, Vickery BP, Zhong X, Burks AW. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009 Aug;124(2):292-300, 300.e1-97. doi: 10.1016/j.jaci.2009.05.022. Epub 2009 Jul 3.
• Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, Hiegel A, Kamilaris J, Carlisle S, Yue X, Kulis M, Pons L, Vickery B, Burks AW. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011 Mar;127(3):654-60. doi: 10.1016/j.jaci.2010.12.1111.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: April 12, 2013
• First Submitted That Met QC Criteria: April 12, 2013
• First Posted (Estimate): April 17, 2013

Study Record Updates

• Last Update Posted (Estimate): June 17, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Walnut hypersensitivity; Tree nut hypersensitivity
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Nut Hypersensitivity
• Other Study ID Numbers: 13-1289

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No