Double-blind, Placebo-controlled, Cross-over Trial of Ketotifen in Children and Adolescents With Functional Dyspepsia in Association With Duodenal Eosinophilia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Respiratory Rate
研究概览
简要总结
Acid reduction remains the most common treatment prescribed empirically by pediatric gastroenterologists for children with functional dyspepsia (FD). When acid reduction therapy fails to provide patients with a therapeutic effect, ketotifen and cromolyn, mast cell stabilizers, represent an attractive potential therapy given data implicating mast cells in the generation of dyspeptic symptoms. Although there have been no adult or pediatric studies on the use of mast cell stabilizers in patients with FD, benefit has been demonstrated in adults with IBS and children with eosinophilic gastroenteritis. Additionally, previous studies show mucosal eosinophilia is highly correlated with functional dyspepsia. Our usual current treatment pathway for functional dyspepsia in association with duodenal mucosal eosinophilia is as follows: acid-reducing medication/montelukast → addition of H1 antagonist → addition of budesonide → addition of oral cromolyn. If ketotifen is effective, it offers the advantage of being able to replace both the H1 antagonist and the oral cromolyn at a substantially reduced cost (approximately 10% of the cost of cromolyn alone). This study aims to introduce ketotifen earlier in the treatment pathway to examine its efficacy on children with functional dyspepsia in association with duodenal eosinophilia.
详细描述
This study is a double-blind, placebo-controlled, cross-over trial of ketotifen in children ages 8 through 17 inclusive that have a diagnosis of functional dyspepsia and have had continued abdominal pain despite acid reduction therapy in combination with montelukast. The primary aim is to assess the symptomatic response to ketotifen as compared to placebo in children with functional dyspepsia in association with duodenal eosinophilia who have previously had worsening, no clinical change, or only a partial response to acid-reduction therapy in combination with montelukast.
The study lasts 147 days for subjects responsive to ketotifen and 63 days for those who are not. For those who respond to ketotifen, there are 4 clinic visits and 3 phone interviews. Clinic visits include a physical, blood draws, questionnaires, review of medical history and medications; phone interviews involve answering a few questions. For those who do not respond to ketotifen, there are 3 clinic and 2 phone visits. Subjects who enroll in the study are randomly assigned to Group A or Group B. The subject, subject's parents, and study staff will not know to which group the subject is assigned. Group A will be given a placebo, an inactive pill with no medication in it, for days 1-28, and switched to ketotifen for days 36-63. Group B will be given ketotifen for days 1-28 and switched to placebo for days 36-63. The group assignment will be unblinded at day 63, at which point initial ketotifen responders will undergo an open-label twelve week trial of ketotifen to assess sustainability.
Secondary aims include: 1) assessing the impact of ketotifen as compared to placebo on quality of life; 2) assessing the sustainability of response to ketotifen in initial responders, and 3) assessing the pharmacokinetics of ketotifen in this patient population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •between the ages of 8 and 17 years, inclusive
- •abdominal pain of at least 8 weeks duration and fulfilling symptom-based criteria for functional dyspepsia(5);
- •previous endoscopy with biopsies demonstrating >20 eosinophils/high powered field on duodenal mucosal biopsies;
- •previous treatment with acid-reduction therapy and montelukast with a level 3 (as defined below)or lesser response;
- •evidence of written parental permission (consent) and subject assent;
- •Negative pregnancy screening for females of child bearing potential.
排除标准
- •previous treatment with ketotifen;
- •treatment with oral corticosteroids or oral cromolyn sodium in the 6 months prior to enrollment;
- •any prior history of diabetes mellitus, cancer, chronic cardiac disease, respiratory disease, or renal disease requiring routine medical care;
- •Pregnant/planning to become pregnant;
- •Post-menarche females unwilling to use highly-efficacious contraception to prevent pregnancy;
- •Epilepsy or history of seizures;
- •Liver disease or elevation of liver enzymes;
- •Use of oral hypoglycemic medications, antipsychotics, benzodiazepines, tricyclic antidepressants, barbiturates, or opioids;
- •Allergy to ketotifen or other products in capsule
- •Refusal of Urine pregnancy test in post-menarchal females.
研究组 & 干预措施
cross-over of Ketotifen
Patients will begin the active ketotifen treatment first and cross over to placebo.
干预措施: Ketotifen (Drug)
cross-over of Placebo
Patients will begin the placebo treatment first and cross over to the active ketotifen.
干预措施: Placebo (Drug)
结局指标
主要结局
Respiratory Rate
时间窗: day 0, day 28, day 63, and day 147
A trained professional will measure respiratory rate to ensure value is within normal range and patient safety. Change is assessed from each time period.
Blood pressure
时间窗: day 0, day 28, day 63, and day 147
A trained professional will measure blood pressure to ensure value is within normal range and ensure safety of patient. Change is assessed from each time period.
Heart Rate
时间窗: day 0, day 28, day 63, and day 147
A trained professional will measure heart rate to ensure value is within normal range and patient safety. Change is assessed from each time period.
Complete Physical
时间窗: day 0, day 28, day 63, and day 147
The study physician will check all systems and ask questions about pain and symptoms. This is a comprehensive system check to ensure safety. Change is assessed from each time period.
Liver Functioning Test (a test ran from a blood sample to check a patients liver functioning)
时间窗: day 0, day 28, day 63, and day 147
A blood sample is collected and tested by a certified laboratory for liver function. This will be completed and verified to be within normal ranges by the study physician to ensure patient safety. Change is assessed from each time period.
State-Trait Inventory for Cognitive and Somatic Anxiety - Child Version
时间窗: day 0, day 28, day 63, and day 147
Anxiety score testing assessed with questionnaires. Anxiety scores are correlated with pain. Change is assessed from each time period.
Pediatric Quality of Life Inventory
时间窗: day 0, day 28, day 63, and day 147
Quality of life survey for pediatrics to ensures maintenance of quality of life throughout study. Change is assessed from each time period.
次要结局
- Pharmacokinetic Sampling (Area under the plasma concentration versus time curve - AUC)(day 0, day 28, day 63, and day 147)
- Pharmacokinetics Sampling (Peak Plasma Concentration - Cmax)(day 0, day 28, day 63, and day 147)
研究者
Craig A. Friesen, MD
Division Chief Gastroenterologist
Children's Mercy Hospital Kansas City