Walnut Oral Immunotherapy for Tree Nut Allergy

NCT ID: NCT01546753

Last Updated: 2023-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-27
• Study Completion Date: 2020-07-02

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.

Conditions

Tree Nut Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Walnut Protein Powder

38 weeks on active walnut powder on blinded treatment phase

Group Type: EXPERIMENTAL

Walnut Protein Powder

Intervention Type: DRUG

Blinded study product dosing begins with a 1-day oral desensitization protocol to walnut for subjects in the active arm. Starting at 0.1 mg protein and increasing to a maximum of 6 mg or until allergic symptoms develop. Subjects continue daily dosing of blinded OIT (walnut) with build-up every 2 weeks to a maximum daily dose of 1500mg at week 34, followed by 4 weeks of daily maintenance dosing. OFC to walnut and second tree nut occurs at week 38 then treatment is unblinded and open-label maintenance dosing occurs.

Oat Powder

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

Group Type: PLACEBO_COMPARATOR

Oat Powder (placebo)

Intervention Type: DRUG

Blinded study product dosing begins with a one-day oral desensitization protocol with placebo (oat) powder. Subjects in the placebo group will undergo the same protocol as those in the active group with placebo OIT dosing. Unblinding to treatment assignment will occur after the 38 week oral food challenge. Placebo subjects will cross-over to active, open-label treatment with walnut powder after the 38 week oral food challenge. beginning with initial escalation day, through build-up and maintenance dosing per the same protocol sequence as noted for active, walnut powder. Subjects will complete an oral food challenge to walnut and the second tree nut at week 38 then will continue on long-term, open-label maintenance dosing until the end of study using same protocol design.

Open-label Walnut Protein Powder

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

Group Type: OTHER

Open-label Walnut Protein Powder

Intervention Type: DRUG

Open-label treatment phase begins after the 38 week oral food challenge with unblinding of treatment assignment. For those on active treatment, daily maintenance dosing occurs for up to a total of 298 weeks. For those on placebo treatment, cross-over to active, open-label treatment occurs using the same active treatment protocol. Placebo-crossover subjects will complete an oral food challenge to walnut and the second tree nut at week 38 of active therapy then continue on long-term, open-label maintenance dosing until the end of study using same protocol design. All subjects may reach a qualifying IgE to walnut/second tree nut early and will undergo an OFCs on and 4 weeks off OIT. All subjects will have OFCs on and 4 weeks off OIT at week 142 and at week 298, unless both walnut/second tree nut OFCs are passed at previous OFC prompting addition of these foods into the diet.

Interventions

Walnut Protein Powder

Blinded study product dosing begins with a 1-day oral desensitization protocol to walnut for subjects in the active arm. Starting at 0.1 mg protein and increasing to a maximum of 6 mg or until allergic symptoms develop. Subjects continue daily dosing of blinded OIT (walnut) with build-up every 2 weeks to a maximum daily dose of 1500mg at week 34, followed by 4 weeks of daily maintenance dosing. OFC to walnut and second tree nut occurs at week 38 then treatment is unblinded and open-label maintenance dosing occurs.

Intervention Type: DRUG

Oat Powder (placebo)

Blinded study product dosing begins with a one-day oral desensitization protocol with placebo (oat) powder. Subjects in the placebo group will undergo the same protocol as those in the active group with placebo OIT dosing. Unblinding to treatment assignment will occur after the 38 week oral food challenge. Placebo subjects will cross-over to active, open-label treatment with walnut powder after the 38 week oral food challenge. beginning with initial escalation day, through build-up and maintenance dosing per the same protocol sequence as noted for active, walnut powder. Subjects will complete an oral food challenge to walnut and the second tree nut at week 38 then will continue on long-term, open-label maintenance dosing until the end of study using same protocol design.

Intervention Type: DRUG

Open-label Walnut Protein Powder

Open-label treatment phase begins after the 38 week oral food challenge with unblinding of treatment assignment. For those on active treatment, daily maintenance dosing occurs for up to a total of 298 weeks. For those on placebo treatment, cross-over to active, open-label treatment occurs using the same active treatment protocol. Placebo-crossover subjects will complete an oral food challenge to walnut and the second tree nut at week 38 of active therapy then continue on long-term, open-label maintenance dosing until the end of study using same protocol design. All subjects may reach a qualifying IgE to walnut/second tree nut early and will undergo an OFCs on and 4 weeks off OIT. All subjects will have OFCs on and 4 weeks off OIT at week 142 and at week 298, unless both walnut/second tree nut OFCs are passed at previous OFC prompting addition of these foods into the diet.

Intervention Type: DRUG

Other Intervention Names

WOIT; Oat flour; Open-label treatment

Eligibility 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Arkansas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stacie M Jones, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas for Medical Sciences / Arkansas Children's Hospital

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19577283 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19477496 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21093029 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21377034 (View on PubMed)

Other Identifiers

FARE

Identifier Type: OTHER

Identifier Source: secondary_id

113364

Identifier Type: -

Identifier Source: org_study_id