Functional dyspepsia (FD)
Conditions
Interventions
Trade Name: Nortrilen
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Trade Name: Nortrilen
Pharmaceutical Form: Capsule
Phar
Sponsors
Maastricht University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with functional dyspepsia (FD), diagnosed according to the Rome IV criteria - Age 18-65 years - Predicted CYP2D6 extensive metabolizer phenotype on the basis of CYP genotyping - In the presence of alarm symptoms, patients are required to have undergone a upper gastrointestinal endoscopy (without evidence of organic disease), and have tested negative for Helicobacter pylori 2 years prior to inclusion. - Insufficient effect of first line treatment with proton pump inhibitors or prokinetics. - Women in their fertile age (=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - History of gastric ulcer; - Evidence of current anxiety and/or depression disorder as defined by a score = 10 on the GAD-7 and/or PHQ-9 questionnaire, supported by a detailed interview by the investigator (i.e. the investigator is required to confirm suspicion of anxiety or depressive disorder); - Predicted CYP2D6 poor, intermediate or ultrarapid metabolizer phenotype on the basis of CYP genotyping - Current use or any previous use of psychotropic medication in the last 3 months prior to inclusion; - Inability to discontinue prokinetics*, NSAIDs or opioids; - Excessive alcohol consumption, defined as > 2 of 3 units per day (females and males respectively) - Using drugs of abuse; - Previous major abdominal surgery or radiotherapy interfering with gastrointestinal function: a. Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months; b. Other surgery upon judgment of the principle investigator; - History of liver disease, cholangitis, achlorhydria, gallstones or other diseases of the gallbladder/biliary system; - Pregnancy or lactation. - History of epilepsy - History of glaucoma * Patients still using prokinetics at the time of inclusion will be asked to discontinue treatment. A wash-out period of 2 weeks before the run-in period is required. Patients that cannot discontinue prokinetic therapy will be excluded. Patients on proton pump inhibitors should continue these without altering dosage, given that rebound symptoms can occur with discontinuation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of an escalating dose regimen of nortriptyline as compared to placebo in FD patients without evidence of significant psychiatric disease, that have been identified as extensive metabolizers based on their CYP2D6 genotype;Secondary Objective: 1. To evaluate the effect of treatment on quality of life, as compared to placebo. 2. To evaluate the cost-effectiveness of treatment, as compared to placebo. 3. To evaluate the effect of treatment after discontinuation, as compared to placebo. 4. To evaluate side-effects of nortriptyline as compared to placebo;Primary end point(s): 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. This is in line with the FDA guidelines on IBS treatment studies. Recorded symptoms include the five core symptoms of FD: epigastric pain, epigastric burning, postprandial fullness, early satiety and upper abdominal bloating. Weeks 1 and 2 are excluded in order to allow for establishment of steady-state drug levels;Timepoint(s) of evaluation of this end point: Weekly evaluation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Self-reported weekly global adequate relief of symptoms (defined as a "yes" in at least 50% of weeks 3-12 of the treatment), collected electronically. Weeks 1 and 2 are excluded in order to allow for establishment of steady-state drug levels - Quality of life, assessed with the use of the EQ-5D-5L (change from baseline). - Dyspepsia-specific quality of life, assessed with the use of the Nepean Dyspepsia Index (change from baseline). - Cost-utility, as determined by calculations incorporating total treatment costs and changes in EQ-5D-5L (QALYs gained) and MCQ/PCQ results (savings from reduced medical resource use and increased work productivity respectively). - Use of rescue medication. - Number and severity of side effects - Responder rates following discontinuation of treatment at 6 months follow-up, as defined by a “Yes” to the query regarding adequate relief from baseline symptoms. - Worst-case-analysis: imputing a non-response day for each day on which the electronic diary entry was missing (due to non-reporting of the patient) in patients assigned to nortriptyline; in patients assigned to placebo, a response day will be imputed for each day the electronic diary entry was missing. - (Negative) mood; assessed with the use of the PHQ-9 and GAD-7 (change from baseline).;Timepoint(s) of evaluation of this end point: 1 - Daily symptom evaluation (symptom diary) with calculation of symptom average at the end of treatment 2 Prior to initiation of the treatment period, at 12 weeks and at 3 and 6 months follow-up 3 Prior to initiation of the treatment period, at 4, 8, 12 weeks and at 3 and 6 months follow-up 4 for MCQ: Prior to initiation of the treatment period, at 12 weeks and at 3 and 6 months follow-up 4 for PCQ: Prior to initiation of the treatment period, at 4, 8, 12 weeks and at 3 and 6 months follow-up 5 + 6 - daily evaluation 7 - at follow-up 8 - end of treatment 9 - Prior to initiation of the treatment period, at 12 weeks of treatment | — |
Countries
Netherlands
Contacts
Public ContactApplicant
Maastricht University Medical Center
Outcome results
None listed