A Phase II Pilot Study to Assess the Safety and Tolerability of Mast Cell Treatment in Post-tick Bite Illness
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Mast Cell Activation Symptom Score
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Fexofenadine Monotherapy
Participants receive fexofenadine 180 mg orally once daily for 4 months following a 14-day open-label run-in period
干预措施: fexofenadine (Drug)
Mast Cell-Directed Combination Therapy
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.
干预措施: Ketotifen (Drug)
Mast Cell-Directed Combination Therapy
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.
干预措施: Cromolyn Sodium (Drug)
Mast Cell-Directed Combination Therapy
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.
干预措施: fexofenadine (Drug)
结局指标
主要结局
Change in Mast Cell Activation Symptom Score
时间窗: 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.
次要结局
- Change in General Symptoms Questionnaire-30 (GSQ-30) Total Score(Baseline, after 4 months of intervention)