Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02365168 |
| Other study ID # |
2013/757(REK) |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
August 19, 2014 |
| Last updated |
December 14, 2015 |
| Start date |
September 2014 |
| Est. completion date |
September 2015 |
Study information
| Verified date |
December 2015 |
| Source |
University Hospital of North Norway |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Norway:National Committee for Medical and Health Research EthicsNorway: Directorate of HealthNorway: Ministry of Health and Care Services |
| Study type |
Interventional
|
Clinical Trial Summary
Study hypothesis:
Some children and adolescents with fish allergy can tolerate eating some species of fish
Purpose of the study:
The purpose of this study is to determine to which degree fish allergic children and
adolescents can tolerate some species of fish and find the minimal eliciting allergen dose
to which only 10% of participants get allergic reaction.
Participants:
Participants are 40 patients recruited from children and adolescents outpatient clinics at
the University Hospital of North Norway with a history of fish allergy and sensibilisation
of one or more fish species with either positive specific IgE in serum or skin prick test.
Patients with sensibilisation to one or more fish species that never have eaten fish are
also recruited.
Method:
- All participants undergo a clinical examination including lung function test with
spirometry before inclusion in the study.
- All participants are tested for allergic sensibilisation with measure of specific IgE
against common food and inhalation allergens in addition to 10 different fish species.
- All participants are challenged with cod, salmon, mackerel and placebo, disguised in a
chocolate mousse. The challenges are performed in randomized order with Double Blind
Placebo Controlled Food Challenge (DBPCFC) on 4 different challenge days with minimum 6
weeks in between each challenge day.
- Participant with allergy to pollen will not be challenged during pollen season.
- Test food is developed especially to this study in cooperation with The National
Institute of Food Research in Norway and The University of Manchester. The National
Institute of Food Research in Norway have produced a dried powder of cod, salmon and
mackerel. The "Molecular Allergology group at Manchester Institute of Biotechnology,
the University of Manchester, have produced test kits based on chocolate mousse
containing low and high doses of the fish powders. The National Institute of Food
Research have measured protein content and microbiology in the fish powders. The
Molecular Allergology group have provided quality measurements of the final product and
tested the disguise in a sensoric test panel.
- Participants with no allergic reaction to one or more of the blinded challenges undergo
open food challenge with larger doses of cooked fish than used in the DBPCFC, after the
randomization has been broken.
Description:
Introduction:
Fish have an important role in human food providing a valuable source of highly assimilated
proteins and consumption of fish is increasing all over the world. Fish allergy is one of
the most common food allergies together with milk, egg, nuts, peanuts, fruits, wheat, soy
and seafood. It is more common in coastal countries and countries with traditions in fish
industry and where fish plays an important role in food traditions. This is the situation in
Northern Norway where fishing and fish industry have been the most important way to make a
living and fish an important part of the food. Allergy to fish is particularly common in
children and young adults. The symptoms related to fish allergy vary from mild symptoms to
anaphylaxis. Most patients with fish allergy avoid all species of fish and health care
workers often advice them to do so. The major allergen in fish is a muscle parvalbumin
resistant to heat, chemical denaturation and proteolytic enzymes. Due to homology in the
amino acid sequence in parvalbumins in different fish species, cross-reactivity exists.
However, clinical experience, studies on sensibilisation, and some open food challenge
studies indicates that some patients with fish allergy can tolerate some species of fish.
The main purpose of this study is to find to which degree fish allergic children and
adolescents can tolerate some species of fish, using DBPCFC as the gold standard in
diagnosis of food allergy, and thereby avoid unnecessary food restrictions in their diet.
The food industry often label their products with "main contain allergen" because they lack
information about threshold doses for allergic reactions. Unnecessary labeling of food
results in less variation in the diet for food allergic patients. Another purpose of this
study is to find the Minimal Eliciting Dose to which 10% of the participants get allergic
reaction, and thereby contribute to a more precise labeling of food.
Method:
DBPCFC is the gold standard in the diagnosis of food allergy. To disguise the taste and
smell from fish in a standardized test food with good taste and texture is difficult. It is
especially difficult with children, who are less likely to eat food with bad taste and where
the volume of test food they can manage is limited.
In cooperation with The National Institute of Food Research in Norway we have produced dried
fish powders from cod, salmon and mackerel. Frozen filets have been cooked, dried and made
into powders. The powders have been checked for microbiologic content and protein content.
The procedure involves removing as much fat as possible. The powders are stored in a freezer
with a temperature of -20°C. The volume is decreased with about 80% compared with cooked
fish.
In cooperation with Professor Clare Mills in the Molecular Allergology group, Manchester
Institute of Biotechnology, The University of Manchester, the fish powders is put into a
chocolate dessert based on a recipe used in a EuroPrevall study on food allergy. The
production of chocolate desserts is performed at the University of Manchester together with
quality check regarding allergen content, content of parvalbumin, microbiology and
speciation of the fish. The disguise of taste and smell are tested in a sensoric test panel.
Recruitment of participants:
Patients aged 5-20 yr, with a history of fish allergy and sensibilisation to fish who had
visited one of the outpatient clinics for children and adolescents at the university
hospital of Northern Norway, are invited to participate. Patients with sensibilisation to
fish that never have eaten fish are also invited. In addition, patients registered with
sensibilisation against cod at the allergology lab, University Hospital of Northern Norway
since 2008 , that not already had been picked up from an outpatient clinic is invited to
participate. The laboratory is the only allergology laboratory in the region the
participants are recruited from.
Examination before inclusion:
All patients that give their consent to participate undergo clinical examination, including
spirometry, before inclusion to ensure eligibility. The clinical examination contains
measurements of weight and height, heart and lung auscultation, examination of skin,
conjunctiva, nose and oral cavity.
Special attention is given to uncontrolled asthma and eczema and to ensure optimized
treatment before inclusion. Pollen allergic patients will not undergo food challenges during
pollen season.
Measurement of specific Immunoglobulin E (IgE) in serum:
In all participants, specific IgE in serum against the following allergens are measured:
1. Fx5 (Egg, milk, cod, wheat, soy, peanut)
2. Inhalation panel 6 (Birch, timothy, mugwort, alternaria, cladosporium)
3. Inhalation panel 7(Cat, horse, dog, house dust mite, rabbit)
4. Gad c1, f426 (Parvalbumin from cod)
5. Cyp c1, f355 (Parvalbumin from carp)
6. Salmon, f41
7. Mackerel, f206
8. Halibut, f303
9. Pollock, f413
10. Haddock, f42
11. Herring, f205
12. Plaice,4254
13. Tuna, f40
14. Shrimp,f24
15. f351 (recombinant shrimp tropomyosin)
Questionnaire:
Parents answer a questionnaire for research in allergy. The questionnaire is translated to
Norwegian and an electronic survey is used. The parents answer the questionnaire during the
first challenge day. The questionnaire is extended with questions regarding fish allergy.
Double Blind Placebo Controlled Food Challenge with cod, salmon, mackerel and placebo:
All participants undergo DBPCFC with cod, salmon, mackerel and placebo in randomized order,
disguised in a chocolate dessert on 4 separate challenge days with minimum 6 weeks between
each challenge day. Participants that have experienced anaphylaxis, verified and treated in
hospital , are not challenged with the species that have given anaphylaxis. Symptoms are
recorded on a clinical manifestations record sheet based on a protocol from the University
Hospital of South Manchester with grading of the symptoms and defined stop criteria. The
protein doses are based on the experience of a EuroPrevall study with DBPCFC with cod:
3µg, 600µg, 12mg, 120mg and1g for DBPCFC
Open challenges with cod and/or salmon and mackerel:
Participants that have no allergic reactions after DBPCFC with either cod, salmon and
mackerel, undergo open challenge(s) with 2 g, 6 g and 12 g of protein , served as cooked
fish, with the species that gave negative DBPCFC. The open challenges are done on separate
days after the randomization code has been broken.
Ceasing of medication before DBPCFC and open challenges:
Systemic corticosteroid therapy are ceased at least one week before challenges.
Antihistamine treatment are ceased at least 72 hours before the challenges. Short acting β-2
agonists are ceased at least 6 hours before the challenges and Long acting β-2 agonists at
least 24 hours before the challenges. Participants are allowed to continue inhalant
corticosteroids and leukotriene receptor antagonists.
Postponing of DBPCFC and open challenges:
The challenges are postponed if the participants have ongoing infections, ongoing allergic
reactions, uncontrolled eczema or uncontrolled asthma. Participants with pollen allergy are
not challenged during pollen season.
Observation and treatment of allergic reactions:
All fish challenges are performed at the research unit at the University Hospital of North
Norway in the period of September 2014 - February 2015. Two participants are challenged each
challenge day and all participants are observed by one blinded research nurse. Unblinded
staff prepare the test meals every morning. One blinded doctor examines the participants
before, during and after the challenges and decides whether challenges are positive or
negative. The challenges are stopped if participants develop objective signs of allergic
reactions. Stop criteria are predefined. Participants are observed in the hospital at least
two hours after the challenges have been stopped. Allergic and anaphylactic reactions are
treated according to European Academy of Allergology and Clinical Immunology position paper
of Anaphylaxis. Participants are contacted by blinded research nurse by phone next day to
record late reactions after discharge.
