Walnut Oral Immunotherapy for Tree Nut Allergy

Phase 1

Completed

Conditions: Tree Nut Allergy

Interventions: Drug: Oat Powder (placebo)
Drug: Walnut Protein Powder
Drug: Open-label Walnut Protein Powder

Registration Number: NCT01546753

Lead Sponsor: University of Arkansas

Brief Summary: The purpose of this study is to determine if walnut oral immunotherapy can be used in participants allergic to tree nuts to reduce tree nut allergy and induce changes in the participant's immune system.

Detailed Description: Randomized, placebo controlled, Phase 1-2 study conducted at Arkansas Children's Hospital Research Institute (ACHRI) in tree nut allergic participants, ages 6-45 years with randomization following a 2:1 (active:placebo) format. The overall objectives were to evaluate the efficacy of walnut oral immunotherapy (WOIT) for induction of desensitization to walnut (secondary outcome) and a test tree nut (primary outcome) when compared to placebo after 38 weeks of treatment as assessed by double-blind, placebo-controlled food challenges (DBPCFC) to walnut and a test tree nut in tree nut allergic participants (defined by allergic reaction to \</= 2 grams of walnut and test tree nut proteins during DBPCFC at study entry). Placebo participants were crossed-over to active therapy after unblinding at week 38. Participants were followed long-term (up to 6 years) on open-label WOIT treatment and assessed at yearly intervals based on pre-specified criteria for clinical outcomes of desensitization to walnut and a test tree nut (defined as safely consuming 5 grams of walnut and test tree nut protein during DBPCFC while on daily WOIT) and sustained unresponsiveness to walnut and a test tree nut (defined as safely consuming 5 grams of walnut and test tree nut protein during DBPCFC and 10 grams during an open feeding while off therapy for 4-6 weeks). Secondary outcomes were evaluated including safety and immune mechanistic parameters.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Oat Powder	Oat Powder (placebo)	38 weeks on placebo (oat) powder during blinded treatment phase
Walnut Protein Powder	Walnut Protein Powder	38 weeks on active walnut powder on blinded treatment phase
Open-label Walnut Protein Powder	Open-label Walnut Protein Powder	Open-label treatment with walnut protein powder up to week 298 of total treatment

Primary Outcome Measures

Name	Time	Method
Effectiveness of Walnut OIT on Clinical Desensitization to Test Tree Nut as Measured by Change in Cumulative Tolerated Dose From Baseline to Week 38 at Oral Food Challenge	38 weeks of therapy	Determine in tree nut allergic subjects the effectiveness of walnut oral immunotherapy on clinical desensitization to a second tree nut ("test tree nut") causing allergy when compared to placebo treatment, as measured by the change in cumulative dose from baseline oral food challenge (OFC) to the OFC to the test tree nut at approximately 38 weeks on therapy.

Secondary Outcome Measures

Name	Time	Method
Evaluation of Desensitization to Walnut Protein as Measured by Change in Cumulative Tolerated Dose From Baseline to Week 38 Oral Food Challenge	38 weeks	Determine in tree nut allergic subjects the effectiveness of walnut oral immunotherapy on clinical desensitization to walnut causing allergy when compared to placebo treatment, as measured by the change in cumulative dose from baseline oral food challenge (OFC) to the OFC to the walnut at approximately 38 weeks on therapy.
Number (Percentage) of Subjects Reaching a Cumulative Tolerated Dose of 2000mg Walnut Protein at Desensitization OFC at Week 38	38 weeks	The percentage of subjects reaching a cumulative protein dose of 2000mg at the desensitization oral food challenge to walnut at week 38
Number (Percentage) of Subjects Reaching a Cumulative Tolerated Dose of 2000mg Test Tree Nut Protein at Desensitization OFC at Week 38	38 weeks	Comparison of the number and percentage of subjects in each treatment arm reaching a cumulative protein dose of 2000mg at the week 38 (desensitization) oral food challenge to test tree nut
Number (Percentage) of Subjects Attaining Sustained Unresponsiveness to Walnut and Test Tree Nut Proteins at Week 298 Oral Food Challenge	up to 298 weeks on active treatment	The percentage of subjects demonstrating sustained unresponsiveness to walnut and to the test tree nut by end of study. Analysis group combines both active and placebo-crossover participants during open-label extension arm through the end of study at week 298. Subjects were able to exit the study at assessment timepoints earlier than week 298 if they are able to pass the sustained unresponsiveness oral food challenge, thus the analysis included all subjects through week 298..
Change in Skin Prick Test Wheal Size From Baseline to Week 142 in Active and Placebo Cross-over Subjects Receiving Active Walnut OIT	142 weeks	Evaluation of walnut OIT on the mast cell responses as measured through change in skin prick testing to walnut in participants who were treated with walnut OIT to week 142. Analysis group combines both active and placebo-crossover participants from baseline through open-label treatment phase until the end of study.
Serious Adverse Events Related to Walnut OIT Treatment	298 weeks active treatment	Incidence of treatment-related serious adverse events during the study

Trial Locations

Locations (1): Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States