Peanut HypersensitivityPhase 2Ex-FactorNCT01429896
The Effect of Extrinsic Factors on Food Allergy
A Phase 2 study testing Food challenge in people with Peanut Hypersensitivity, run by Cambridge University Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
Food allergy is a common problem, affecting 5-8% of the population. Peanut allergy causes reduced quality of life due to the perceived high risk of severe reactions. Patients rely on accurate labeling of both loose and pre-packed foods, but these are often ambiguous and unhelpful. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Peanut Hypersensitivity
- What is being tested?
- Food challenge
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Oct 2012to Oct 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Male and female subject who are 18-45 years of age at the time of study entry (Visit 1) who have a diagnosis of acute peanut allergy as manifested by urticaria, angioedema or respiratory/gastrointestinal tract symptoms, with acute onset of symptoms after ingestion (up to 2h).
- A positive peanut DBPCFC at baseline (Visit 1). This outcome is defined as the onset of objective allergic events after ingestion of peanut protein but not to the placebo. Eligibility to the DBPCFC requires fulfillment of all other eligibility criteria at visit 1.
- Subjects must be able to comply with the study procedures.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
Addenbrooke's Hospital
Cambridge, Cambs, CB2 2QQ
Andrew T Clark, MB BS MD
- Recruiting
Imperial College
London, London, W2 1PG
Robert Boyle, MB BS PhD
About this study
Food allergy is a common problem, affecting 5-8% of the population. Peanut allergy causes reduced quality of life due to the perceived high risk of severe reactions. Patients rely on accurate labeling of both loose and pre-packed foods, but these are often ambiguous and unhelpful. There is a common conception that labeling is 'over-cautious'. Peanut-allergic consumers face increasingly restricted food choices in complying with this advice due, in part, to the proliferation of advisory labels such as 'may contain peanuts'. This contributes to the reduces quality of life of affected individuals.
For industry to provide more accurate and helpful labeling, certain characteristics of the food-allergic population need to be defined. Firstly, the minimum 'eliciting dose' for the population has been estimated by studying large groups of peanut allergic patients who are challenged with peanut ingestion in increasing amounts. From these, an eliciting dose that provokes a reaction in 10% of the food-allergic population has been estimated at between six and 14mg of peanut protein.
Translation of population eliciting doses (ED) into acceptable levels of allergen contamination for the population requires consideration of a 'safety factor'- to account for individual variability in dose threshold and severity. Data suggest such variability depends in part on extrinsic factors (exercise and sleep restriction). Each factor may have a different effect in scale and direction. The investigators are proposing a cross-over trial with 85 peanut-allergic adults who will each undergoing a baseline peanut challenge followed by repeat challenges with extrinsic factors applied, in random order (repeat baseline, +exercise and +sleep restriction). These data will further define ED for the UK population and a safety factor derived from shift in threshold, to inform industry and protect the allergic population.
Read the detailed description
N=100 subjects will undergo a baseline challenge to peanut without exacerbating extrinsic factors. These initial baseline challenges will be performed when asthma is well controlled (validated by normal spirometry values), the subject is rested and there is no evidence of viral illness (clinical history and examination). A two-day double blind placebo controlled peanut challenge (DBPCPC) will be performed. Subjects receive either all placebo doses or all active doses on one of two days. Each day consists of all eight doses separated by 20 minute intervals (3microg to 1g). The active doses are hidden in a carrier which has been assessed for blinding efficacy. Subjective and objective dose threshold and severity score for challenge outcome will be recorded. Subjects will receive detailed written and verbal advice to avoid peanut until the next challenge. All subjects will be asked to carry oral antihistamines and injectable adrenaline.
All participants who have a clinical reaction during the initial baseline DBPCFC will be randomized to one of 6 balanced cross over intervention sequences from a Latin square design. Each group rotates through three further challenges in a different order: control (no extrinsic factor), exercise and sleep restriction.
- Control challenge Subjects must not have had any accidental reaction to peanut in the previous three months. This challenge will be performed when asthma is well controlled (validated by spirometry normal values), the subjects are rested (sleep diary for preceding week will be examined) and there is no viral illness (clinical history and examination). A peanut challenge will be performed (identically to the initial baseline DBPCFC). Dose threshold and severity score for challenge outcome will be recorded.
- Exercise challenge Subjects undergo a repeat challenge to peanut with exercise as an extrinsic factor, a minimum of three months after the previous challenge. Subjects must not have had any accidental reaction to peanut in the previous three months. This challenge will be performed when asthma is well controlled (validated by spirometry normal values for the individual and clinical history), the subjects are rested, and there is no viral illness.
The challenge will be double blind and placebo controlled. The challenge will take place on two occasions, on one day all four doses will contain placebo only, on the second all four doses will be active (peanut). The subjects will undergo an identical exercise protocol on both days.
On each day the challenge will begin with 15 minutes of exercise using a standardised protocol. Following this the first challenge dose is given. This is followed by 20 minutes of rest (and observation) before a further exercise period followed by ingestion of the second dose and so on.
The active doses will be…
- 1/100th of the threshold identified at the initial baseline challenge
- 1/10th of the threshold identified at the initial baseline challenge
- The threshold dose identified at the control challenge
- One dose increment higher than the dose identified at the control challenge.
Subjective and objective dose thresholds and severity score for challenge outcome will be recorded.
If there is no reaction to any dose on the active day then the active arm will be repeated on a separate day, starting at the lowest available challenge dose (3 micrograms). Dose increments up to at least 1/100th of the threshold identified at the control challenge will follow.
- Sleep restriction
Participants will undergo a repeat double blind placebo controlled challenge to peanut including sleep restriction as an extrinsic factor, a minimum of three months from the last challenge. Subjects must not have had any accidental reaction to peanut in the previous three months. This challenge will be performed when asthma is well controlled (validated by spirometry normal values), and there is no viral illness (clinical history and examination).
Subjects will be admitted to the research ward on the evening prior to the challenge. Overnight, sleep will be restricted to 3 hours (2300-0200). Subjects will undergo a peanut challenge, using the same dosing range and intervals as the initial baseline challenge.
Subjective and objective dose thresholds and severity score for challenge outcome will be recorded on central online data store. The challenge will take place on two occasions, on one day all doses will contain placebo only, on the second all doses will be active (peanut). The subjects will undergo an identical sleep restriction protocol on each day.
- Conditions
- Peanut Hypersensitivity
- Being tested
- Food challenge
- Keywords
- peanut allergy, food allergy, thresholds, anaphylaxis, food labelling, food challenges, peanut challenges
- Medical subject headings
- Peanut Hypersensitivity, Food Hypersensitivity, Anaphylaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Food challengeOther
Also called Threshold extrinsic factor challenges
Double blind placebo controlled peanut challenge. Each challenge given with or without extrinsic factors exercise or sleep restriction.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Exercise followed by sleep restriction followed by control challenge Receives: Other: Food challenge |
| Arm 2 | Experimental | Sleep restriction followed by exercise followed by control challenge Receives: Other: Food challenge |
| Arm 3 | Experimental | control followed by sleep restriction followed by exercise Receives: Other: Food challenge |
| Arm 4 | Experimental | control followed by exercise followed by sleep restriction Receives: Other: Food challenge |
| Arm 5 | Experimental | Sleep Restriction followed by control followed by exercise Receives: Other: Food challenge |
| Arm 6 | Experimental | Exercise followed by control followed by sleep restriction Receives: Other: Food challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
minimum amount of peanut protein in milligrams which causes an objective clinical reaction during peanut challenges
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2011 (estimated)
- Study startOct 2012
- Primary completionSep 2015 (estimated)
- Study completionOct 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Peanut HypersensitivityStudies 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 2
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London, University of Manchester
- Responsible party
- Principal investigator, Dr. Andrew Clark, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Andrew T Clark, MB BS MD, Study director, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01429896
- Sponsor's protocol ID
- 01.31.09.2011
- Acronym
- Ex-Factor
- Status last verified
- Jan 2015
- First submitted
- 31 Aug 2011
- Last updated
- 14 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Avery NJ, King RM, Knight S, Hourihane JO. Assessment of quality of life in children with peanut allergy. Pediatr Allergy Immunol. 2003 Oct;14(5):378-82. doi: 10.1034/j.1399-3038.2003.00072.x.
PubMed 14641608Dua S, Ruiz-Garcia M, Bond S, Durham SR, Kimber I, Mills C, Roberts G, Skypala I, Wason J, Ewan P, Boyle R, Clark A. Effect of sleep deprivation and exercise on reaction threshold in adults with peanut allergy: A randomized controlled study. J Allergy Clin Immunol. 2019 Dec;144(6):1584-1594.e2. doi: 10.1016/j.jaci.2019.06.038. Epub 2019 Jul 15.
PubMed 31319102
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Extrinsic Factors on Food Allergy
- ClinicalTrials.gov ID
- NCT01429896
- Acronym / sponsor ID
- Ex-Factor / 01.31.09.2011
- Conditions
- Peanut Hypersensitivity
- Keywords
- peanut allergy, food allergy, thresholds, anaphylaxis, food labelling, food challenges, peanut challenges
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Imperial College London, University of Manchester
- Study start
- Oct 2012
- Primary completion
- Sep 2015 (estimated)
- Study completion
- Oct 2015 (estimated)
- First posted
- 7 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Food allergy is a common problem, affecting 5-8% of the population. Peanut allergy causes reduced quality of life due to the perceived high risk of severe reactions. Patients rely on accurate labeling of both loose and pre-packed foods, but these are often ambiguous and unhelpful. There is a common conception that labeling is 'over-cautious'. Peanut-allergic consumers face increasingly restricted food choices in complying with this advice due, in part, to the proliferation of advisory labels such as 'may contain peanuts'. This contributes to the reduces quality of life of affected individuals.
For industry to provide more accurate and helpful labeling, certain characteristics of the food-allergic population need to be defined. Firstly, the minimum 'eliciting dose' for the population has been estimated by studying large groups of peanut allergic patients who are challenged with peanut ingestion in increasing amounts. From these, an eliciting dose that provokes a reaction in 10% of the food-allergic population has been estimated at between six and 14mg of peanut protein.
Translation of population eliciting doses (ED) into acceptable levels of allergen contamination for the population requires consideration of a 'safety factor'- to account for individual variability in dose threshold and severity. Data suggest such variability depends in part on extrinsic factors (exercise and sleep restriction). Each factor may have a different effect in scale and direction. The investigators are proposing a cross-over trial with 85 peanut-allergic adults who will each undergoing a baseline peanut challenge followed by repeat challenges with extrinsic factors applied, in random order (repeat baseline, +exercise and +sleep restriction). These data will further define ED for the UK population and a safety factor derived from shift in threshold, to inform industry and protect the allergic population.
Detailed description
N=100 subjects will undergo a baseline challenge to peanut without exacerbating extrinsic factors. These initial baseline challenges will be performed when asthma is well controlled (validated by normal spirometry values), the subject is rested and there is no evidence of viral illness (clinical history and examination). A two-day double blind placebo controlled peanut challenge (DBPCPC) will be performed. Subjects receive either all placebo doses or all active doses on one of two days. Each day consists of all eight doses separated by 20 minute intervals (3microg to 1g). The active doses are hidden in a carrier which has been assessed for blinding efficacy. Subjective and objective dose threshold and severity score for challenge outcome will be recorded. Subjects will receive detailed written and verbal advice to avoid peanut until the next challenge. All subjects will be asked to carry oral antihistamines and injectable adrenaline.
All participants who have a clinical reaction during the initial baseline DBPCFC will be randomized to one of 6 balanced cross over intervention sequences from a Latin square design. Each group rotates through three further challenges in a different order: control (no extrinsic factor), exercise and sleep restriction.
- Control challenge Subjects must not have had any accidental reaction to peanut in the previous three months. This challenge will be performed when asthma is well controlled (validated by spirometry normal values), the subjects are rested (sleep diary for preceding week will be examined) and there is no viral illness (clinical history and examination). A peanut challenge will be performed (identically to the initial baseline DBPCFC). Dose threshold and severity score for challenge outcome will be recorded.
- Exercise challenge Subjects undergo a repeat challenge to peanut with exercise as an extrinsic factor, a minimum of three months after the previous challenge. Subjects must not have had any accidental reaction to peanut in the previous three months. This challenge will be performed when asthma is well controlled (validated by spirometry normal values for the individual and clinical history), the subjects are rested, and there is no viral illness.
The challenge will be double blind and placebo controlled. The challenge will take place on two occasions, on one day all four doses will contain placebo only, on the second all four doses will be active (peanut). The subjects will undergo an identical exercise protocol on both days.
On each day the challenge will begin with 15 minutes of exercise using a standardised protocol. Following this the first challenge dose is given. This is followed by 20 minutes of rest (and observation) before a further exercise period followed by ingestion of the second dose and so on.
The active doses will be…
- 1/100th of the threshold identified at the initial baseline challenge
- 1/10th of the threshold identified at the initial baseline challenge
- The threshold dose identified at the control challenge
- One dose increment higher than the dose identified at the control challenge.
Subjective and objective dose thresholds and severity score for challenge outcome will be recorded.
If there is no reaction to any dose on the active day then the active arm will be repeated on a separate day, starting at the lowest available challenge dose (3 micrograms). Dose increments up to at least 1/100th of the threshold identified at the control challenge will follow.
- Sleep restriction
Participants will undergo a repeat double blind placebo controlled challenge to peanut including sleep restriction as an extrinsic factor, a minimum of three months from the last challenge. Subjects must not have had any accidental reaction to peanut in the previous three months. This challenge will be performed when asthma is well controlled (validated by spirometry normal values), and there is no viral illness (clinical history and examination).
Subjects will be admitted to the research ward on the evening prior to the challenge. Overnight, sleep will be restricted to 3 hours (2300-0200). Subjects will undergo a peanut challenge, using the same dosing range and intervals as the initial baseline challenge.
Subjective and objective dose thresholds and severity score for challenge outcome will be recorded on central online data store. The challenge will take place on two occasions, on one day all doses will contain placebo only, on the second all doses will be active (peanut). The subjects will undergo an identical sleep restriction protocol on each day.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Other: Food challengeExercise followed by sleep restriction followed by control challenge |
| Arm 2 | Experimental | Other: Food challengeSleep restriction followed by exercise followed by control challenge |
| Arm 3 | Experimental | Other: Food challengecontrol followed by sleep restriction followed by exercise |
| Arm 4 | Experimental | Other: Food challengecontrol followed by exercise followed by sleep restriction |
| Arm 5 | Experimental | Other: Food challengeSleep Restriction followed by control followed by exercise |
| Arm 6 | Experimental | Other: Food challengeExercise followed by control followed by sleep restriction |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Written informed consent must be obtained before any assessment is performed.
- Male and female subject who are 18-45 years of age at the time of study entry (Visit 1) who have a diagnosis of acute peanut allergy as manifested by urticaria, angioedema or respiratory/gastrointestinal tract symptoms, with acute onset of symptoms after ingestion (up to 2h).
- A positive peanut DBPCFC at baseline (Visit 1). This outcome is defined as the onset of objective allergic events after ingestion of peanut protein but not to the placebo. Eligibility to the DBPCFC requires fulfillment of all other eligibility criteria at visit 1.
- Subjects must be able to comply with the study procedures.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Food challengeAlso: Threshold extrinsic factor challengesDouble blind placebo controlled peanut challenge. Each challenge given with or without extrinsic factors exercise or sleep restriction. | Other | Arm 1, Arm 2, Arm 3, Arm 4, Arm 5, Arm 6 |
Primary outcome
minimum amount of peanut protein in milligrams which causes an objective clinical reaction during peanut challenges
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2015.
- Background: PubMed 14641608Avery NJ, King RM, Knight S, Hourihane JO. Assessment of quality of life in children with peanut allergy. Pediatr Allergy Immunol. 2003 Oct;14(5):378-82. doi: 10.1034/j.1399-3038.2003.00072.x.
- Derived from this study: PubMed 31319102Dua S, Ruiz-Garcia M, Bond S, Durham SR, Kimber I, Mills C, Roberts G, Skypala I, Wason J, Ewan P, Boyle R, Clark A. Effect of sleep deprivation and exercise on reaction threshold in adults with peanut allergy: A randomized controlled study. J Allergy Clin Immunol. 2019 Dec;144(6):1584-1594.e2. doi: 10.1016/j.jaci.2019.06.038. Epub 2019 Jul 15.
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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.
Andrew T Clark, MB BS MD study director
Cambridge University Hospitals NHS Foundation Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Food challenge in people with Peanut Hypersensitivity, run by Cambridge University Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
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 4 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 14 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrew T Clark, MB BS MD (+44 1223 762603, andrew.clark@addenbrookes.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
minimum amount of peanut protein in milligrams which causes an objective clinical reaction during peanut challenges (time frame: 36 months). 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 NCT01429896, which also lists 2 linked publications.
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 14 Jan 2015.