Tailored Treatment of Functional Dyspepsia With Nortriptyline: a Multi-center Double-blind Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 96
- 试验地点
- 14
- 主要终点
- Symptom response
研究概览
简要总结
Functional dyspepsia (FD) is a common functional gastrointestinal disorder characterized by upper abdominal discomfort/pain and/or symptoms of meal-related fullness/satiety. There is currently no definitive therapy that is beneficial for all FD patients. Accumulating evidence suggests efficacy of tricyclic antidepressants (TCAs) in FD. However, no firm conclusion can be drawn currently due to the relatively small amount of studies and large heterogeneity between studies. In addition, TCAs are often associated with side effects, which occur early after initiation of therapy preceding the therapeutic effect and often result in discontinuation of the therapy. These side effects are related to drug metabolism, which depend on polymorphisms of the cytochrome P (CYP) enzyme system. It is therefore hypothesized that pre-treatment assessment of CYP genotype and subsequent exclusion of abnormal metabolizers limits the occurrence of side-effects and as such improves compliance and efficacy.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years;
- •A diagnosis of FD according to the Rome IV criteria;
- •Predicted CYP2D6 extensive metabolizer phenotype on the basis of CYP genotyping
- •Insufficient effect of first line treatment with proton pump inhibitors (twice daily) or prokinetics;
- •In the presence of alarm symptoms, patients are required to have undergone an upper gastrointestinal endoscopy (without evidence of organic disease), and have tested negative for Helicobacter pylori 2 years prior to inclusion;
- •Women in their fertile age (<55 years old) must use contraception or be postmenopausal for at least two years.
排除标准
- •Predicted CYP2D6 poor, intermediate or ultrarapid metabolizer phenotype on the basis of CYP genotyping
- •Evidence of current anxiety and/or depression disorder as defined by a score ≥ 10 on the GAD-7 and/or PHQ-9 questionnaire;
- •Current use or any previous use of psychotropic medication in the last 3 months prior to inclusion;
- •Inability to discontinue prokinetics, NSAIDs or opioids;
- •Using drugs of abuse;
- •Using more than 2 or 3 units of alcohol per day (females and males respectively)
- •Previous major abdominal surgery or radiotherapy interfering with gastrointestinal function:
- •Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months;
- •Other surgery upon judgment of the principle investigator;
- •History of gastric ulcer;
- •History of liver disease, cholangitis, achlorhydria, gallstones or other diseases of the gallbladder/biliary system;
- •History of epilepsy
- •History of glaucoma
- •Pregnancy or lactation.
研究组 & 干预措施
Nortriptyline
Nortriptyline in an escalating dose regimen:
Week 1-2: 10mg daily Week 3-4: 25mg daily Week 5-12: 50mg daily
干预措施: Nortriptyline (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Symptom response
时间窗: 12 weeks
Response to therapy, as defined by a 30% reduction from baseline (i.e. the run-in period) in the weekly average of daily symptom scores, during at least 50% of weeks 3-12 of treatment. Symptoms will be assessed daily using a digital diary (mobile phone application). Recorded symptoms include the five core symptoms of FD: epigastric pain, epigastric burning, postprandial fullness, early satiety and upper abdominal bloating.
次要结局
- Adequate relief(12 weeks)
- General quality of life(12 weeks, 3 & 6 months)
- Dyspepsia-specific quality of life(12 weeks, 3 & 6 months)
- Cost-utility(12 weeks, 3 & 6 months)
- Use of rescue medication.(12 weeks)
- Number and severity of side effects.(12 weeks)
- Responder rates following discontinuation(6 months)
- Negative mood - anxiety(12 weeks, 3 & 6 months)
- Negative mood - depression(12 weeks, 3 & 6 months)