Post-tick Bite IllnessPhase 2NCT07526558
Mast Cell Treatment in Post-tick Bite Illness (PTBI)
A Phase 2 study testing Ketotifen, fexofenadine and Cromolyn Sodium in people with Post-tick Bite Illness and Mast Cell Stabilizer, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Post-tick Bite Illness, Mast Cell Stabilizer
- What is being tested?
- Ketotifen, fexofenadine and Cromolyn Sodium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2026to Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Julie Vorobiov contact
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27514
Study Coordinator, 800-594-8624, alphagalstudy@med.unc.edu
About this study
Official title: A Phase II Pilot Study to Assess the Safety and Tolerability of Mast Cell Treatment in Post-tick Bite Illness
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).
Read the detailed description
This Phase II study is designed as a randomized, double-blind study to assess the safety, tolerability, and feasibility of mast cell-directed therapy using ketotifen, cromolyn and fexofenadine vs fexofenadine alone in participants who have post-tick bite illness. The study is a 2 arm, 4-month trial preceded by a 14 day run-in period of fexofenadine for all screened and consented participants. At the end of 14 days, participants will be re-administered the mast cell activation symptom screening questionnaire and those who have a greater than 20% increase in symptom improvement score during 14 days of fexofenadine will be considered meaningfully better and not be randomized due to not needing further treatment. Randomized participants (n=50) will be assigned 2:1 by study pharmacy to receive either fexofenadine 180mg daily or ketotifen 1 mg twice daily (starting dose) + cromolyn 200mg three times daily + fexofenadine 180 mg daily. After 30 days, ketotifen will be increased to 2 mg twice daily and remain at that dose until trial completion.
- Conditions
- Post-tick Bite Illness, Mast Cell Stabilizer
- Being tested
- Ketotifen, fexofenadine, Cromolyn Sodium
- Keywords
- post-tick bite illness, mast cell stabilizer, alpha-gal syndrome
- Medical subject headings
- red meat allergy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetotifenDrug
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.
fexofenadineDrug
Also called Allegra
Fexofenadine is a second-generation H1 antihistamine administered orally at a dose of 180 mg once daily
Cromolyn SodiumDrug
Cromolyn sodium is a mast cell stabilizer administered orally at a dose of 200 mg three times daily.
| Study group | Role | What they receive |
|---|---|---|
| Fexofenadine Monotherapy | Active comparator | Participants receive fexofenadine 180 mg orally once daily for 4 months following a 14-day open-label run-in period Receives: 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. Receives: Drug: Ketotifen; Drug: fexofenadine; Drug: Cromolyn Sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, after 4 months of intervention
Secondary outcomes (1)
Change in General Symptoms Questionnaire-30 (GSQ-30) Total Score
The General Symptoms Questionnaire-30 (GSQ-30) is a 30-item patient-reported outcome measure designed to assess multi-system symptom burden. Each item is rated on a 5-point Likert scale from 0 ("not at all") to 4 ("very much"), resulting in a total score ranging from 0 to 120. Higher scores indicate greater symptom burden.
Measured: Baseline, after 4 months of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2026
- Study start30 Apr 2026 (estimated)
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-tick Bite IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Columbia University
- Responsible party
- Sponsor
- Investigators
- Scott Commins, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07526558
- Sponsor's protocol ID
- 24-0990
- Status last verified
- Apr 2026
- First submitted
- 6 Apr 2026
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Pilot Study to Assess the Safety and Tolerability of Mast Cell Treatment in Post-tick Bite Illness
- ClinicalTrials.gov ID
- NCT07526558
- Acronym / sponsor ID
- 24-0990
- Conditions
- Post-tick Bite Illness, Mast Cell Stabilizer
- Keywords
- post-tick bite illness, mast cell stabilizer, alpha-gal syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Columbia University
- Study start
- 30 Apr 2026 (estimated)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 13 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This Phase II study is designed as a randomized, double-blind study to assess the safety, tolerability, and feasibility of mast cell-directed therapy using ketotifen, cromolyn and fexofenadine vs fexofenadine alone in participants who have post-tick bite illness. The study is a 2 arm, 4-month trial preceded by a 14 day run-in period of fexofenadine for all screened and consented participants. At the end of 14 days, participants will be re-administered the mast cell activation symptom screening questionnaire and those who have a greater than 20% increase in symptom improvement score during 14 days of fexofenadine will be considered meaningfully better and not be randomized due to not needing further treatment. Randomized participants (n=50) will be assigned 2:1 by study pharmacy to receive either fexofenadine 180mg daily or ketotifen 1 mg twice daily (starting dose) + cromolyn 200mg three times daily + fexofenadine 180 mg daily. After 30 days, ketotifen will be increased to 2 mg twice daily and remain at that dose until trial completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fexofenadine Monotherapy | Active comparator | Drug: fexofenadineParticipants receive fexofenadine 180 mg orally once daily for 4 months following a 14-day open-label run-in period |
| Mast Cell-Directed Combination Therapy | Experimental | Drug: Ketotifen, Drug: fexofenadine, Drug: Cromolyn SodiumParticipants 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. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- 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
Key exclusion criteria (12 listed)
- Any individual who meets one or more of the following criteria will be excluded from participation:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetotifenKetotifen 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. | Drug | Mast Cell-Directed Combination Therapy |
| fexofenadineAlso: AllegraFexofenadine is a second-generation H1 antihistamine administered orally at a dose of 180 mg once daily | Drug | Fexofenadine Monotherapy, Mast Cell-Directed Combination Therapy |
| Cromolyn SodiumCromolyn sodium is a mast cell stabilizer administered orally at a dose of 200 mg three times daily. | Drug | Mast Cell-Directed Combination Therapy |
Primary outcome
Change in Mast Cell Activation Symptom Score
Time frame: Baseline, after 4 months of intervention
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.
1 secondary outcome
Change in General Symptoms Questionnaire-30 (GSQ-30) Total Score
Time frame: Baseline, after 4 months of intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Individual participant dataSharing planned: Yes. Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Julie Vorobiov contact
Scott Commins principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketotifen, fexofenadine and Cromolyn Sodium in people with Post-tick Bite Illness and Mast Cell Stabilizer, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Scott P Commins, MD, PhD (919-537-3306, scommins@email.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mast Cell Activation Symptom Score (time frame: Baseline, after 4 months of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.