The Role of Uric Acid Metabolism in Anaphylaxis: the Effect of Allopurinol on Allergic Reactions to Peanut in Peanut Allergic Adults.

Phase 1

• Conditions: Determination of the Lowest Observed Adverse Event level dose (LOAEL)of peanut in individual suffering with peanut allergy, after treatment with allopurinol.; MedDRA version: 20.0 Level: LLT Classification code 10001738 Term: Allergy System Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.0 Level: PT Classification code 10016946 Term: Food allergy System Organ Class: 10021428 - Immune system disorders; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2017-005060-18-GB
• Lead Sponsor: Manchester University NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-09
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

All of the below must apply:
1.Males and females 18-55 years
2.Capable of giving informed consent
3.Previous medical history of allergic reaction to peanut
4.Doctor’s diagnosis of peanut allergy (either reported in the previous medical history or diagnosis of peanut allergy at the screening visit -V1- by a physician other than the study doctor, as described in the trial Case Report Forms).
5.Reaction history should not be solely indicative of oral allergy syndrome (that is, only localised symptoms in and/or around the oral cavity)
6.Positive skin prick test result to peanut > 3mm and/or specific IgE to peanut =0.4kUa/L (ImmunoCAP Phadia)
7.Participant able to swallow capsules
8.Baseline systolic blood pressure of equal or over 100mmHg
9.Participant should be able to receive the following rescue medication, if needed (They should not have a contraindication to the use of this medication, as per study doctor’s judgement).
-Inhaled and IV salbutamol;
-inhaled and IM adrenaline;
-oral and IV antihistamines;
-Inhaled, oral or other systemic (e.g parenteral) corticosteroids.
10.Negative HLA-B*5801 status
11.Positive result on the peanut day of the DBPCFC (visits two and three), and the positive result to be on any dose up to and including the 100mg dose of peanut protein.
12.Negative challenge result on the placebo day of the DBPCFC (visits two and three).

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Any of the below excludes someone from participating:
1.Females must be non-pregnant with no intention of becoming pregnant during the study.
Women of childbearing potential (<1 year post-menopausal) must agree to use (or are already on) one of the following acceptable birth control methods whilst they are enrolled in the trial:
-True complete abstinence when this is in line with the preferred and usual lifestyle of the participant;
-surgical sterilisation of either the female participant in the study or of her male partner, if he is the sole partner of the participant;
-established hormonal contraception (implantable, patch, oral or intramuscular [IM]) administered for at least one month prior to study medication administration;
-intrauterine device (IUD) or intrauterine system (IUS) with a failure rate of less than 1% per year inserted by a qualified physician, at least one month prior to study medication administration;
-double barrier method: condom and occlusive cap (diaphragm) with spermicidal foam/gel/film/cream/suppository

2.Serum pregnancy test will be conducted at screening, and urine pregnancy tests (sticks) will be conducted at all other visits apart from the two follow-up visits. In the event of a positive test, the participant will be withdrawn from the trial and the pregnancy will be reported to the Sponsor.

3.Females must be non-lactating.
Reports indicate that allopurinol and oxypurinol are excreted in human breast milk. Concentrations of 1.4 mg/litre allopurinol and 53.7 mg/litre oxypurinol have been demonstrated in breast milk from a woman taking allopurinol 300 mg/day. There is no data regarding the effects of allopurinol or its metabolites on the breastfed baby.

4.The participants should not be on medication that is contraindicated for the IMP or for the procedures of the trial:
These are:
-(due to interactions with allopurinol): Salicylates (e.g Aspirin), Uricosuric agents (e.g. febuxostat, probenecid), Phenytoin, Theophylline, Ampicillin, amoxicillin (e.g co-amoxiclav), Coumarin Anticoagulants (e.g. warfarin), Immunosuppressant and immunomodulatory drugs (e.g 6-mercaptopurine, azathioprine, cyclophosphamide, cyclosporin), doxorubicin, bleomycin, procarbazine, mechlorethamine, Antiretroviral drugs (e.g Didanosine), diuretics, Chlorpropamide, Captopril, Vidarabine (adenine arabinoside), ACE inhibitors.
-(due to interference with the study design): Beta-blocking agents, ACE inhibitors, Oral or other systemic corticosteroids, anti-IgE (omalizumab), SSRI antidepressant medication.

Also, the participant should not be on allopurinol.

5.Participants should not have participated in other clinical trials involving the use of an Investigational Medicinal Product (IMP) within the past 3 months.
6.There should be no previous history of a severe allergic reaction to peanut with confirmed lower respiratory symptoms or documented hypotension.
7.FEV1 should be no less than 70% predicted for age, gender and height
8.Participants should not be unable or unlikely to follow the trials procedures due to any issue (including communication issues such as language barrier).
9.The participant s

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified