Tree Nut AllergyPhase 1/2WOITNCT01546753
Walnut Oral Immunotherapy for Tree Nut Allergy
A Phase 1/2 study testing Walnut Protein Powder and Open-label Walnut Protein Powder in people with Tree Nut Allergy, run by University of Arkansas at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 45 years
- Conditions the study is for
- Tree Nut Allergy
- What is being tested?
- Walnut Protein Powder and Open-label Walnut Protein Powder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Apr 2012to 2 Jul 2020
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
United States1 site
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
About this study
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.
Read the 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
- Being tested
- Walnut Protein Powder, Oat Powder (placebo), Open-label Walnut Protein Powder
- Keywords
- Walnut allergy, Tree nut allergy, Oral immunotherapy, Food allergy, Desensitization, Sustained unresponsiveness
- Medical subject headings
- Nut Hypersensitivity, Food Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Walnut Protein PowderDrug
Also called WOIT
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 (placebo)Drug
Also called Oat flour
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 PowderDrug
Also called Open-label treatment
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.
| Study group | Role | What they receive |
|---|---|---|
| Walnut Protein Powder | Experimental | 38 weeks on active walnut powder on blinded treatment phase Receives: Drug: Walnut Protein Powder |
| Oat Powder | Placebo comparator | 38 weeks on placebo (oat) powder during blinded treatment phase Receives: Drug: Oat Powder (placebo) |
| Open-label Walnut Protein Powder | Other | Open-label treatment with walnut protein powder up to week 298 of total treatment Receives: Drug: Open-label Walnut Protein Powder |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: 38 weeks of therapy
Secondary outcomes (6)
Evaluation of Desensitization to Walnut Protein as Measured by Change in Cumulative Tolerated Dose From Baseline to Week 38 Oral Food Challenge
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.
Measured: 38 weeks
Number (Percentage) of Subjects Reaching a Cumulative Tolerated Dose of 2000mg Walnut Protein at Desensitization OFC at Week 38
The percentage of subjects reaching a cumulative protein dose of 2000mg at the desensitization oral food challenge to walnut at week 38
Measured: 38 weeks
Number (Percentage) of Subjects Reaching a Cumulative Tolerated Dose of 2000mg Test Tree Nut Protein at Desensitization OFC at Week 38
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
Measured: 38 weeks
Number (Percentage) of Subjects Attaining Sustained Unresponsiveness to Walnut and Test Tree Nut Proteins at Week 298 Oral Food Challenge
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..
Measured: up to 298 weeks on active treatment
Change in Skin Prick Test Wheal Size From Baseline to Week 142 in Active and Placebo Cross-over Subjects Receiving Active Walnut OIT
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.
Measured: 142 weeks
Serious Adverse Events Related to Walnut OIT Treatment
Incidence of treatment-related serious adverse events during the study
Measured: 298 weeks active treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study start27 Apr 2012
- Primary completion2 Jul 2015
- Study completion2 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Tree Nut AllergyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Subjects will be randomized in a 2:1 ratio to either active treatment (final dose 1500mg walnut protein (WP), n=20) or placebo (n=10). Subjects will do a 1-day desensitization to enable subjects to tolerate 6 mg of WP or placebo (initial day escalation). After the initial escalation day obtaining at least 1.5mg and up to 6mg of WP or placebo, dosing build-up will be every 2 wks thru dose 24 (34 wks). A maintenance dose will be given for 4 wks, then a 5g protein OFC to walnut \& a 5g protein OFC to a 2nd tree nut (\~38 wks), then the study will be unblinded. Placebo subjects that fail the OFC will cross-over to active treatment and escalate to 1500mg target dose. Subjects will be followed for 298 wks (\~6 yrs) total on active treatment including an OFC (both on \& off therapy) to walnut and 2nd tree nut at 142 wk \& end of study. Subjects with reduced serum specific IgE to \<5kU/L to walnut and 2nd tree nut at yearly visits before the end of study at 298 wks are eligible for a tolerance OFC.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stacie M Jones, MD, Principal investigator, University of Arkansas for Medical Sciences / Arkansas Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01546753
- Sponsor's protocol ID
- 113364
- Other IDs
- FARE
- Acronym
- WOIT
- Status last verified
- Apr 2023
- First submitted
- 1 Mar 2012
- Last updated
- 12 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 19577283Hofmann 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.
PubMed 19477496Kulis 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.
PubMed 21093029Varshney 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.
PubMed 21377034