Mast Cell Treatment in Post-tick Bite Illness (PTBI)

NCT07526558 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-0990
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II double-blinded study to assess the safety, tolerability, and feasibility of the mast cell stabilizing medications ketotifen and cromolyn compared to participants receiving standard of care treatment with fexofenadine alone in participants who have persistent symptoms of mast cell activation following a documented tick-borne illness (Ehrlichiosis, Rocky Mountain Spotted Fever, Alpha-gal Syndrome).

Conditions

Post-tick Bite Illness; Mast Cell Stabilizer

Keywords

post-tick bite illness; mast cell stabilizer; alpha-gal syndrome

Outcome Measures

Primary Outcomes (1)

• Change in Mast Cell Activation Symptom Score

  Symptoms will be assessed using the mast cell activity symptom scale, which is based on the American Academy of Allergy, Asthma and Immunology scale but with modifications to include neuro/psych symptoms. The construct is a Likert metric with participants ranking symptoms based on categories of frequency, severity and impact to daily life ("bothersome"). Each item is rated on a 4-point scale from 1 ("not at all") to 4 ("extremely") resulting in a range of 63 - 252. Higher scores are correlated with worse symptoms.

  Baseline, after 4 months of intervention

Secondary Outcomes (1)

• Change in General Symptoms Questionnaire-30 (GSQ-30) Total Score

  Baseline, after 4 months of intervention

Study Arms (2)

Fexofenadine Monotherapy

ACTIVE COMPARATOR

Participants receive fexofenadine 180 mg orally once daily for 4 months following a 14-day open-label run-in period

Drug: fexofenadine

Mast Cell-Directed Combination Therapy

EXPERIMENTAL

Participants receive ketotifen plus cromolyn plus fexofenadine for 4 months following a 14-day open-label run-in period. Ketotifen is administered orally at 1 mg twice daily with dose escalation to 2 mg twice daily after 30 days. Cromolyn is administered orally at 200 mg three times daily, and fexofenadine is administered orally at 180 mg once daily.

Drug: Ketotifen; Drug: fexofenadine; Drug: Cromolyn Sodium

Interventions

Cromolyn Sodium DRUG

Cromolyn sodium is a mast cell stabilizer administered orally at a dose of 200 mg three times daily.

Mast Cell-Directed Combination Therapy

Ketotifen DRUG

Ketotifen is a mast cell stabilizer and H1 antihistamine administered orally at 1 mg twice daily, with dose escalation to 2 mg twice daily after 30 days.

Mast Cell-Directed Combination Therapy

fexofenadine DRUG

Fexofenadine is a second-generation H1 antihistamine administered orally at a dose of 180 mg once daily

Also known as: Allegra

Fexofenadine Monotherapy; Mast Cell-Directed Combination Therapy

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Ability to understand and provide informed consent in English (a translator will not be present during screening, consent or follow-up visits)
• Age 21-65 years old and of any gender, race, and ethnicity at the time of the initial visit.
• History of Ehrlichiosis and/or Rocky Mountain Spotted Fever (RMSF) within the last 36 months diagnosed and treated by a healthcare provider more than 6 months previously with current symptoms causing clinically significant distress or impairment in functioning as measured by a mast cell symptom scale score \>88 ± 9
• OR - History of alpha-gal syndrome (AGS) with an alpha-gal Immunoglobulin E (IgE) \>0.1 IU/mL and managed on an appropriate avoidance diet for more than 6 months previously with current symptoms causing clinically significant distress or impairment in functioning as measured by a mast cell symptom scale score \>88 ± 9
• Females of childbearing potential must have a negative pregnancy test prior to study entry
• Ability to refrain from diphenhydramine ("Benadryl") during the study period

You may not qualify if:

• Any individual who meets one or more of the following criteria will be excluded from participation:
• History of allergy, intolerance or hypersensitivity to fexofenadine, cromolyn or ketotifen (as documented by self-report and/or medical chart review)
• History of a prior course of ketotifen and/or cromolyn within 12 months before enrollment
• Inability or unwillingness to give written informed consent or comply with study protocol
• Pregnant (urine testing) or planning to become pregnant during the course of this study
• Use of omalizumab within 6 months of enrollment
• Use of systemic steroids for any reason within 28 days of study entry
• Use of zileuton within 14 days of study entry
• Have past or current medical problems or findings from physical exam or laboratory testing not listed above, which in the opinion of the investigator, may pose additional risks from participation in the study or which may interfere with the ability to comply with study requirements
• Suicidal ideation with intent in the last 6 months or suicidal behavior in the last year as assessed by the Columbia-suicide severity rating scale
• Current serious unstable medical illness
• Ongoing or planned other therapies to address post-tick bite illness (PTBI) symptoms during the course of this study

Sponsors & Collaborators

• Columbia University: collaborator
• University of North Carolina, Chapel Hill: lead

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

red meat allergy

Interventions

Ketotifen; fexofenadine; Cromolyn Sodium

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Scott Commins

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Scott P Commins, MD, PhD

CONTACT

919-537-3306; scommins@email.unc.edu

Julie Vorobiov

CONTACT

alphagalstudy@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: April 13, 2026
• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: beginning 9 and continuing for 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (1)