Pilot Study to Evaluate the Effect of Ketotifen on the Adverse Events Associated With Peanut Desensitization

A Prospective, Randomized, Case Controlled, Pilot Study to Evaluate the Effect of Ketotifen on the Adverse Events Associated With Peanut Desensitization in Children With Peanut Allergies.

The primary objective of this study is to evaluate, compared to non-treatment, the impact of a titrated dose (1 mg once a day, then 1 mg twice a day and finally a full 2 mg twice a day) of ketotifen on the adverse event profile emerging from a rapid peanut desensitization protocol, in children with established peanut allergy.

Study Overview

• Status: Unknown
• Conditions: Peanut Allergies in Children
• Intervention / Treatment: Drug: Ketotifen

Detailed Description

The development of a safe oral peanut challenge procedure permits patients that do not have severe life threatening allergic reactions, to be safely desensitized with the ability to maintain peanut tolerance . The peanut desensitization procedure is however associated with unpleasant allergic side effects mainly gastrointestinal and cutaneous manifestations. The use of premedication drugs may lessen these side effects and facilitate the peanut desensitization procedure. Ketotifen is a fast acting, noncompetitive, H1-receptor blocker (antihistamine/inverse agonist) that also inhibits the release of mediators from mast cells involved in hypersensitivity reactions.

The study will enroll 6 (4 in the peanut treatment group, 2 in the control group) children with a known history of peanut allergies. The treated subjects will be randomized in a 2:1 ratio into either a pre-treatment group (final dose of 2 mg bid ketotifen) or a control group. All subjects will undergo a one-day peanut desensitization protocol designed to enable the subject to tolerate 50 mg of peanut flour (initial escalation phase). After the initial escalation day achieving up to 50 mg of peanut flour, the dosing build-up will occur every two weeks through 44 weeks. Subjects will ingest the 50mg and increased doses of peanut flour at home (every day for 2 weeks) between each dose escalation. The target dose is 8000 mg of peanut flour. A maintenance dose will be given for 4 weeks following the last (highest dose) visit.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4V 1R2
      • GSCRI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 8 years, all of either sex, any race, any ethnicity at the time of the initial visit
• The presence of IgE specific to peanuts (a positive skin prick test to peanuts (diameter of wheal >3.0 mm) and a positive in vitro IgE [CAP-FEIA] > 7 kUA/L
• A history of significant clinical symptoms occurring within 60 minutes after ingesting peanuts
• Provide signed informed consent.

Exclusion Criteria:

1. History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise (Cyanosis or SpO2 < 92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence)
2. Currently participating in a study using an investigational new drug
3. Participation in any interventional study for the treatment of food allergy in the past 12 months
4. Subjects with a known oat or wheat (because of potential cross contamination with oat) food allergy will be excluded
5. Poor control or persistent activation of atopic dermatitis
6. Moderate to severe persistent asthma
7. Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the NHLBI guidelines
8. Inability to discontinue antihistamines for skin testing
9. History of epilepsy or seizures
10. Diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Case control; Routine therapy during peanut desensitization
Experimental: ketotifen; rising doses of ketotifen	Drug: Ketotifen; titrated dose: 1 mg once a day, then 1 mg twice a day then 2 mg twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event leading to discontinuation	Treatment with peanut flour causes ADRs that lead to treatment discontinuation.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Assessment	Investigator's assessment of treatment impact on moderating adverse reactions associated with desensitization.	12 months

Collaborators and Investigators

• Sponsor: Gordon Sussman Clinical Research
• Collaborators: Mast Cell Pharmaceuticals Inc.
• Investigators: Principal Investigator: Gordon L Sussman, MD

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Anticipated): September 1, 2012

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (Estimate): June 21, 2012

Study Record Updates

• Last Update Posted (Estimate): June 21, 2012
• Last Update Submitted That Met QC Criteria: June 20, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: peanut allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Ketotifen
• Other Study ID Numbers: MCP-001