Walnut Oral Immunotherapy for Tree Nut Allergy (WOIT)

University of Arkansas

Status and phase: Completed; Phase 2; Phase 1

Conditions: Tree Nut Allergy

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01546753

FARE (Other Identifier)

113364

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 6 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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22 participants in 3 patient groups, including a placebo group

Walnut Protein Powder

Experimental group

Description:

38 weeks on active walnut powder on blinded treatment phase

Treatment:

Drug: Walnut Protein Powder

Oat Powder

Placebo Comparator group

Description:

38 weeks on placebo (oat) powder during blinded treatment phase

Treatment:

Drug: Oat Powder (placebo)

Open-label Walnut Protein Powder

Other group

Description:

Open-label treatment with walnut protein powder up to week 298 of total treatment

Treatment:

Drug: Open-label Walnut Protein Powder