Post-failure Stepwise Heat-Denaturated Protein Introduction for Tolerance Induction in Cow's Milk Allergy Observational Cohort Study (Post-TEHITI)

Subjects who failed to become tolerant within 12 months after randomization within one of the three arms in the TEHITI study, can participate in the post-TEHITI observational trial to study the natural tolerance induction process.

Study Overview

• Status: Recruiting
• Conditions: Cow's Milk Protein Allergy

Detailed Description

In this observational study the investigators will study the time to complete tolerance in cow's milk allergic children who tolerate 20' heated milk but failed the OFC with unheated milk 12 months after passing the 20' boiled cow's milk OFC. Moreoever, the investigators want to document all clinical reactions and potential cofactors during the tolerance induction process. The investigators anticipate that the whole cohort will become tolerant in a time span shorter than 48 months. Therefore the study period in each participant will be 48 months or the period to achieve complete tolerance (which comes first).

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Marleen Jannis; Phone Number: +32016343801; Email: marleen.jannis@uzleuven.be
• Study Contact Backup: Name: Dominique MA Bullens, Prof, MD; Phone Number: +32016343801; Email: dominique.bullens@uzleuven.be

Study Locations

• Belgium
  • Bonheiden, Belgium
    • Recruiting
    • Imelda Hospital
    • Contact: Katrien Coppens, MD
  • Bruges, Belgium
    • Recruiting
    • AZ Sint Jan
    • Contact: Kate Sauer, MD
  • Ghent, Belgium
    • Recruiting
    • AZ Maria Middelares
    • Contact: Jasmine Leus, MD
  • Hasselt, Belgium
    • Recruiting
    • Jessa Hospital
    • Contact: Sophie Verelst, MD
  • Leuven, Belgium
    • Recruiting
    • UZ Leuven Gasthuisberg
    • Contact: Marleen Jannis; Phone Number: +32016343801; Email: marleen.jannis@uzleuven.be
    • Contact: Dominique MA Bullens, Prof, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Children participating in study s68299 who fail the challenge test with unheated cow's milk 12 months after initiation of the TEHITI trial, can be enrolled in this post-TEHITI study. Upon IC (and assent if appropriate) parents (and children) can participate in the current post-TEHITI observational trial. Upon enrollment in the post-TEHITI trial, specific data will be pseudonymised and collected during the clinical follow-up visits:

• Intake of cow's milk containing food products: amount, recipe, frequency of intake in the period between two follow-up consultations
• Clinical reactions: description and recording of potential cofactors for their presentation
• Medication use to treat the clinical reaction
• Relation to cow's milk intake: certain/doubtful/absent
• Specific IgE to cow's milk proteins in peripheral blood
• Total IgE levels in peripheral blood Individual pseudonymisation will be done by similar code as given in TEHITI trial.

Description

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

• participation in s68299
• failure to challenge test with unheated cow's milk
• passed challenge test with unheated cow's milk but with symptoms developing between challenge and termination visit related to cow's milk intake at home

Exclusion Criteria:

Participants eligible for this study must not meet any of the following criteria:

• Subjects not priorly enrolled in s68299
• Subjects enrolled in s68299 who passed the challenge test and have no complaints upon regular cow's milk consumption at termination visit
• Subjects who refuse to consent/assent with the study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants that acquire tolerance for cow's milk after initially failing a cow's milk provocation test	The number of participants that spontaneously acquire tolerance for cow's milk after initially failing a cow's milk provocation test will be counted.	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse clinical reactions to cow's milk protein intake during observational period	Nature and condition of clinical reactions in relation to different heated and/or unheated forms of cow's milk protein intake during observational period	48 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Jessa Hospital; Imelda Hospital, Bonheiden; AZ Sint-Jan AV; Algemeen Ziekenhuis Maria Middelares
• Investigators: Principal Investigator: Jasmine Leus, MD, Maria Middelares Hospital, Gent; Principal Investigator: Katrien Coppens, MD, Imelda Hospital, Bonheiden; Principal Investigator: Kate Sauer, MD, AZ Sint-Jan AV; Principal Investigator: Sophie Verelst, MD, Jessa Hospital, Hasselt and KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2025
• Primary Completion (Estimated): October 24, 2030
• Study Completion (Estimated): October 24, 2030

Study Registration Dates

• First Submitted: November 29, 2024
• First Submitted That Met QC Criteria: February 28, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 28, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: S68469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No