The Effect of Extrinsic Factors on Food Allergy
The Effect of Extrinsic Factors on Food Allergy
Sponsors
Lead Sponsor
Collaborators
Source
Cambridge University Hospitals NHS Foundation Trust
Oversight Info
Has Dmc
Yes
Brief 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. 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.
1. 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.
2. 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. 1/100th of the threshold identified at the initial baseline challenge
2. 1/10th of the threshold identified at the initial baseline challenge
3. The threshold dose identified at the control challenge
4. 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.
3. 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.
Overall Status
Unknown status
Start Date
2012-10-01
Completion Date
2015-10-01
Primary Completion Date
2015-09-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
minimum amount of peanut protein in milligrams which causes an objective clinical reaction during peanut challenges |
36 months |
Enrollment
100
Condition
Intervention
Intervention Type
Other
Intervention Name
Description
Double blind placebo controlled peanut challenge. Each challenge given with or without extrinsic factors exercise or sleep restriction.
Arm Group Label
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Other Name
Threshold extrinsic factor challenges
Eligibility
Criteria
Inclusion Criteria:
- 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.
Gender
All
Minimum Age
18 Years
Maximum Age
45 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Andrew T Clark, MB BS MD |
Study Director |
Cambridge University Hospitals NHS Trust |
Overall Contact
Location
Facility |
Status |
Investigator |
Addenbrooke's Hospital Cambridge Cambs CB2 2QQ United Kingdom |
Recruiting |
Last Name: Andrew T Clark, MB BS MD Role: Principal Investigator |
Imperial College London W2 1PG United Kingdom |
Recruiting |
Last Name: Robert Boyle, MB BS PhD |
Location Countries
Country
United Kingdom
Verification Date
2015-01-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
Cambridge University Hospitals NHS Foundation Trust
Investigator Full Name
Dr. Andrew Clark
Investigator Title
Associate Lecturer and Consultant in Paediatric Allergy
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
6
Arm Group
Arm Group Label
Arm 1
Arm Group Type
Experimental
Description
Exercise followed by sleep restriction followed by control challenge
Arm Group Label
Arm 2
Arm Group Type
Experimental
Description
Sleep restriction followed by exercise followed by control challenge
Arm Group Label
Arm 3
Arm Group Type
Experimental
Description
control followed by sleep restriction followed by exercise
Arm Group Label
Arm 4
Arm Group Type
Experimental
Description
control followed by exercise followed by sleep restriction
Arm Group Label
Arm 5
Arm Group Type
Experimental
Description
Sleep Restriction followed by control followed by exercise
Arm Group Label
Arm 6
Arm Group Type
Experimental
Description
Exercise followed by control followed by sleep restriction
Firstreceived Results Date
N/A
Reference
Citation
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.
PMID
14641608
Acronym
Ex-Factor
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Crossover Assignment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study First Submitted
August 31, 2011
Study First Submitted Qc
September 6, 2011
Study First Posted
September 7, 2011
Last Update Submitted
January 13, 2015
Last Update Submitted Qc
January 13, 2015
Last Update Posted
January 14, 2015
Last Known Status
Recruiting
ClinicalTrials.gov processed this data on December 11, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.