Peanut AllergyPhase 1/2PNOIT2NCT01750879
Tolerance Following Peanut Oral Immunotherapy
A Phase 1/2 study testing Peanut Flour and Oat Flour in people with Peanut Allergy, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The unifying objective of this project is to determine whether peanut oral immunotherapy (PN OIT) induced clinical tolerance in the context of food allergy is significantly associated with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is thought to be inducible in the… Read more about this study
- Who is it for?
- Ages 7 to 55 years
- Conditions the study is for
- Peanut Allergy
- What is being tested?
- Peanut Flour and Oat Flour
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to 11 Jul 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 7 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of peanut allergy by a positive skin prick test to peanut (reaction wheal at least 5 mm larger than saline control) and by medical history or Serum peanut-specific IgE >5 kU/L at screening visit.
- Ara h 2 specific IgE >0.35 kU/L at screening visit
- Ability to provide informed consent.
- Males and females of all ethnic/racial groups aged 7-55 years old who are otherwise healthy.
- React to less than 443 mg of peanut protein during DBPCFC1
Who cannot join
- History of severe anaphylaxis as defined by hypoxia (cyanosis or SpO2 <92% during reaction), documented hypotension (documented systolic BP >30% below predicted normal for sex, height, weight or from known baseline), neurological compromise (confusion, loss of consciousness), or incontinence.
- Severe or Moderate asthma as defined using the severity criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/).
- Poorly-controlled asthma as defined by FEV1 <80% or any of the following symptoms: nighttime awakening >2 days/week or rescue medication use >2 days / week.
- Diagnosis of other severe or complicating medical problems, including autoimmune or chronic immune inflammatory conditions or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders
- Inability to cooperate with and/or perform oral food challenge procedures.
- Primary Immune Deficiency
Show all 12Show fewer
- Allergy to oat confirmed by skin prick testing and history
- Current use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine oxidase inhibitors
- Women of childbearing potential who are pregnant, planning to become pregnant, or breastfeeding
- Hemoglobin level less than 12.5 gm/dL at screening. Weight <23 kg
- Use within the past 6 months of other systemic immunomodulatory treatments including allergen immunotherapy, or use of biologics with an immune target, including omalizumab.
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study may also exclude a participant from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Clinical Desensitization and Tolerance Following Peanut Oral Immunotherapy and Subsequent Allergen Avoidance
The unifying objective of this project is to determine whether peanut oral immunotherapy (PN OIT) induced clinical tolerance in the context of food allergy is significantly associated with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is thought to be inducible in the gut-associated lymphoid compartment and associated with immunological tolerance.
The hypothesis of the study is that the induction of Treg cells will be associated with clinical tolerance.
The investigators will measure the change from baseline of induced Treg cells as a frequency of total CD4 T cells during active treatment and compare that between participants who achieve significant clinical tolerance (Tolerance and Partial Tolerance Groups as defined below) and those who do not (Treatment Failure Group).
Read the detailed description
Clinical Objectives:
- To evaluate whether PN OIT induces increased tolerance, defined as a statistically significant increase in the median eliciting dose (ED) from a double-blind placebo-controlled food challenge (DBPCFC) before and after treatment with PN OIT and after subsequent allergen avoidance.
- To evaluate whether PN OIT induces clinical desensitization, defined as 1) a median 10-fold or greater increase in ED at DBPCFC before and after PN OIT treatment period 2) a statistically significant higher median ED at DBPCFC following treatment period between active and control treatment; and 3) a significantly lower frequency of accidental ingestion reactions in active versus control treatment.
- To evaluate the safety of PN OIT.
Mechanistic Objectives:
- To determine whether PN OIT induces a statistically significant increase in the TCR clonal diversity of Treg populations during active treatment among participants who achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined in clinical endpoints) versus the Treatment Failure Group.
- To determine whether PN OIT suppresses mast cells by inducing a significant suppression of the median ED on end-point dilution skin testing in actively treated participants by the end of maintenance therapy.
- To determine whether PN OIT suppresses basophils as defined by a 10-fold suppression of peanut-specific basophil ED in actively treated participants by end of a maintenance period.
- To determine whether either mast cell or basophil suppression at the end of maintenance therapy is significantly associated with clinical outcomes following avoidance.
Exploratory Objectives:
- To describe the gene expression profiles and clonal diversity of regulatory and effector T cell subsets before and after OIT to better understand the phenotype and ontogeny of these subsets and potentially discover new therapeutic pathways.
- To engineer human MHC class II tetramers on common HLA backgrounds and map T cell epitopes of the dominant peanut allergens for use in validating earlier findings and for future studies of peanut-specific immune responses in humans.
- Conditions
- Peanut Allergy
- Being tested
- Peanut Flour, Oat Flour
- Keywords
- peanut, allergy, food, immunotherapy, tolerance, desensitization
- Medical subject headings
- Peanut Hypersensitivity, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peanut FlourDrug
Peanut Flour
Oat FlourDrug
Oat Flour
| Study group | Role | What they receive |
|---|---|---|
| Peanut Flour | Active comparator | Oral Immunotherapy with peanut flour. Receives: Drug: Peanut Flour |
| Oat Flour | Placebo comparator | Oral Immunotherapy with oat flour. Receives: Drug: Oat Flour |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerance, Partial Tolerance, or Treatment Failure
- Tolerance: Ingestion of 4430 mg of peanut protein at DBPCFC3 without symptoms.
- Partial Tolerance: ED at DBPCFC3 <4430 mg but =>430 mg AND >10-fold more than at DBPCFC1.
- Treatment Failure - non desensitized: Failure to achieve the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED <1443 mg at DBPCFC2, or ED at DBPCFC3 <443 mg OR <10-fold more than at DBPCFC1.
- Treatment Failure - withdrawal
Measured: Average 515 days from DBPCFC1 to DBPCFC3
Secondary outcomes (8)
Clinical: Tolerance
The change in median eliciting dose (ED) from DBPCFC1 to DBPCFC3. (note: ED right censored to maximum dose for those without any clinical reactivity)
Measured: 630 days
Clinical: Desensitization
- The change in median eliciting dose (ED) from DBPCFC1 to DBPCFC2.
Measured: 518 days
Clinical: Safety
- The rate of reported adverse advents due to accidental ingestions in the active versus placebo groups.
Measured: 630 days
Mechanistic: TCR Clonal Diversity
The change in the TCR clonal diversity of in vitro allergen-expanded Treg cells and induced Treg cells measured by TCRB CDR3 sequence clonotyping of sorted cells during active treatment among participants who achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined in clinical endpoints) versus the Treatment Failure Group.
We conducted a nested case-control analysis of a subset of actively treated (by treatment outcome) versus placebo treated patients. Genomic DNA was used to amplify and sequence the complementarity-determining region 3 (CDR3) regions (immunoSEQ assay; Adaptive Biotechnologies).
Enriched clonotypes in the CD154+ fraction (doi: https://doi.org/10.1101/2020.05.11.088286) were analyzed for differences by Rank Abundance Curve analysis (R package alakazam; Chao A, et al. Ecology. 2015 96, 11891201) to determine differences in clonal diversity.
Measured: 630 days
Mechanistic: Change Eliciting Dose of End-point Dilution.
The change in eliciting dose of end-point dilution skin testing between actively treated and placebo treated participants following maintenance therapy and the change in ED of end-point dilution skin testing among actively treated participants following maintenance therapy and avoidance between clinical outcome groups.
Measured: 518 days
Mechanistic: Change in Basophil Eliciting Dose.
The change in peanut-specific basophil ED in actively treated participants at the end of maintenance and the end of avoidance between clinical outcome groups.
Measured: 630 days
Mechanistic: Change in Peanut Allergen-specific IgG4
The change in peanut allergen-specific IgG4 in actively treated participants by the end of maintenance between clinical outcome groups.
Measured: 518 days
Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations
Statistically significant gene expression changes (as number of genes) by transcriptional profiling of regulatory and effector T cell populations before and after OIT between clinical outcome groups.
Total RNA from CD154+ and CD154-CD69- T cells was used for cDNA synthesis and amplification. Libraries were prepared and sequenced to a read depth of approximately 30 million reads per sample (Illumina HiSeq) and aligned to the hg19 human reference genome with the ensemble version 75 annotation using STAR version 2.5.3a,(Dobin et al. Bioinformatics 2013) and gene expression was summarized using RSEM version 1.3.0 (Li et al. BMC Bioinform 2013). Differential expression analysis was performed using DESeq2 v 1.30.1 (R v 4.04). Significance level was set at an unadjusted P value less than .001.
Measured: 630 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study startAug 2013
- Primary completion11 Jul 2017
- Study completion11 Jul 2017
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 (1)Papers the sponsor has linked to this study.
- Other trials for Peanut AllergyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wayne G. Shreffler, MD, PhD, Massachusetts General Hospital
- Investigators
- Wayne G Shreffler, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01750879
- Sponsor's protocol ID
- 2012P002153
- Other IDs
- 5U19AI095261-02
- Acronym
- PNOIT2
- Status last verified
- Jul 2021
- First submitted
- 13 Dec 2012
- Last updated
- 28 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: de-identified data exported from REDCap
Publications
Monian B, Tu AA, Ruiter B, Morgan DM, Petrossian PM, Smith NP, Gierahn TM, Ginder JH, Shreffler WG, Love JC. Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells. J Clin Invest. 2022 Jan 18;132(2):e150634. doi: 10.1172/JCI150634.
PubMed 34813505
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Desensitization and Tolerance Following Peanut Oral Immunotherapy and Subsequent Allergen Avoidance
- ClinicalTrials.gov ID
- NCT01750879
- Acronym / sponsor ID
- PNOIT2 / 2012P002153
- Conditions
- Peanut Allergy
- Keywords
- peanut, allergy, food, immunotherapy, tolerance, desensitization
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Aug 2013
- Primary completion
- 11 Jul 2017 (actual)
- Study completion
- 11 Jul 2017 (actual)
- First posted
- 17 Dec 2012 (estimated)
- Results
- Posted 28 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The unifying objective of this project is to determine whether peanut oral immunotherapy (PN OIT) induced clinical tolerance in the context of food allergy is significantly associated with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is thought to be inducible in the gut-associated lymphoid compartment and associated with immunological tolerance.
The hypothesis of the study is that the induction of Treg cells will be associated with clinical tolerance.
The investigators will measure the change from baseline of induced Treg cells as a frequency of total CD4 T cells during active treatment and compare that between participants who achieve significant clinical tolerance (Tolerance and Partial Tolerance Groups as defined below) and those who do not (Treatment Failure Group).
Detailed description
Clinical Objectives:
- To evaluate whether PN OIT induces increased tolerance, defined as a statistically significant increase in the median eliciting dose (ED) from a double-blind placebo-controlled food challenge (DBPCFC) before and after treatment with PN OIT and after subsequent allergen avoidance.
- To evaluate whether PN OIT induces clinical desensitization, defined as 1) a median 10-fold or greater increase in ED at DBPCFC before and after PN OIT treatment period 2) a statistically significant higher median ED at DBPCFC following treatment period between active and control treatment; and 3) a significantly lower frequency of accidental ingestion reactions in active versus control treatment.
- To evaluate the safety of PN OIT.
Mechanistic Objectives:
- To determine whether PN OIT induces a statistically significant increase in the TCR clonal diversity of Treg populations during active treatment among participants who achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined in clinical endpoints) versus the Treatment Failure Group.
- To determine whether PN OIT suppresses mast cells by inducing a significant suppression of the median ED on end-point dilution skin testing in actively treated participants by the end of maintenance therapy.
- To determine whether PN OIT suppresses basophils as defined by a 10-fold suppression of peanut-specific basophil ED in actively treated participants by end of a maintenance period.
- To determine whether either mast cell or basophil suppression at the end of maintenance therapy is significantly associated with clinical outcomes following avoidance.
Exploratory Objectives:
- To describe the gene expression profiles and clonal diversity of regulatory and effector T cell subsets before and after OIT to better understand the phenotype and ontogeny of these subsets and potentially discover new therapeutic pathways.
- To engineer human MHC class II tetramers on common HLA backgrounds and map T cell epitopes of the dominant peanut allergens for use in validating earlier findings and for future studies of peanut-specific immune responses in humans.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Peanut Flour | Active comparator | Drug: Peanut FlourOral Immunotherapy with peanut flour. |
| Oat Flour | Placebo comparator | Drug: Oat FlourOral Immunotherapy with oat flour. |
Who may qualify
- Ages
- 7 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Diagnosis of peanut allergy by a positive skin prick test to peanut (reaction wheal at least 5 mm larger than saline control) and by medical history or Serum peanut-specific IgE >5 kU/L at screening visit.
- Ara h 2 specific IgE >0.35 kU/L at screening visit
- Ability to provide informed consent.
- Males and females of all ethnic/racial groups aged 7-55 years old who are otherwise healthy.
- React to less than 443 mg of peanut protein during DBPCFC1
Key exclusion criteria (12 listed)
- History of severe anaphylaxis as defined by hypoxia (cyanosis or SpO2 <92% during reaction), documented hypotension (documented systolic BP >30% below predicted normal for sex, height, weight or from known baseline), neurological compromise (confusion, loss of consciousness), or incontinence.
- Severe or Moderate asthma as defined using the severity criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/).
- Poorly-controlled asthma as defined by FEV1 <80% or any of the following symptoms: nighttime awakening >2 days/week or rescue medication use >2 days / week.
- Diagnosis of other severe or complicating medical problems, including autoimmune or chronic immune inflammatory conditions or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders
- Inability to cooperate with and/or perform oral food challenge procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Peanut FlourPeanut Flour | Drug | Peanut Flour |
| Oat FlourOat Flour | Drug | Oat Flour |
Primary outcome
Tolerance, Partial Tolerance, or Treatment Failure
Time frame: Average 515 days from DBPCFC1 to DBPCFC3
1. Tolerance: Ingestion of 4430 mg of peanut protein at DBPCFC3 without symptoms. 2. Partial Tolerance: ED at DBPCFC3 <4430 mg but =>430 mg AND >10-fold more than at DBPCFC1. 3. Treatment Failure - non desensitized: Failure to achieve the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED <1443 mg at DBPCFC2, or ED at DBPCFC3 <443 mg OR <10-fold more than at DBPCFC1. 4. Treatment Failure - withdrawal
8 secondary outcomes
Clinical: Tolerance
Time frame: 630 days
Clinical: Desensitization
Time frame: 518 days
Clinical: Safety
Time frame: 630 days
Mechanistic: TCR Clonal Diversity
Time frame: 630 days
Mechanistic: Change Eliciting Dose of End-point Dilution.
Time frame: 518 days
Mechanistic: Change in Basophil Eliciting Dose.
Time frame: 630 days
Mechanistic: Change in Peanut Allergen-specific IgG4
Time frame: 518 days
Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations
Time frame: 630 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34813505Monian B, Tu AA, Ruiter B, Morgan DM, Petrossian PM, Smith NP, Gierahn TM, Ginder JH, Shreffler WG, Love JC. Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells. J Clin Invest. 2022 Jan 18;132(2):e150634. doi: 10.1172/JCI150634.
- Individual participant dataSharing planned: Yes. de-identified data exported from REDCap
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wayne G Shreffler, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Peanut Flour and Oat Flour in people with Peanut Allergy, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerance, Partial Tolerance, or Treatment Failure (time frame: Average 515 days from DBPCFC1 to DBPCFC3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01750879, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2021.