Clinical trial NCT03652571: Nortriptyline for the Treatment of Functional Dyspepsia
Official title: Tailored Treatment of Functional Dyspepsia With Nortriptyline: a Multi-center Double-blind Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Functional Dyspepsia
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2018-08-29
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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:

  1. Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months;
  2. 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.

Primary outcomes:
measure: Symptom response
timeFrame: 12 weeks
Secondary outcomes:
measure: Adequate relief
timeFrame: 12 weeks
measure: General quality of life
timeFrame: 12 weeks, 3 & 6 months
measure: Dyspepsia-specific quality of life
timeFrame: 12 weeks, 3 & 6 months
measure: Cost-utility
timeFrame: 12 weeks, 3 & 6 months
measure: Use of rescue medication.
timeFrame: 12 weeks
measure: Number and severity of side effects.
timeFrame: 12 weeks
measure: Responder rates following discontinuation
timeFrame: 6 months
measure: Negative mood - anxiety
timeFrame: 12 weeks, 3 & 6 months
measure: Negative mood - depression
timeFrame: 12 weeks, 3 & 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: VUmc
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch ziekenhuis
city: Ede
country: Netherlands
facility: Gelderse Vallei
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Hilversum
country: Netherlands
facility: Tergooi Hilversum
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Leiden
country: Netherlands
facility: Alrijne ziekenhuis
city: Maastricht
country: Netherlands
facility: Maastrich University Medical Center
city: Uden
country: Netherlands
facility: Bernhoven
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
city: Veldhoven
country: Netherlands
facility: MMC
Study officials:
affiliation: Maastricht University Medical Center
name: Ad A.A.M Masclee, Prof
role: PRINCIPAL_INVESTIGATOR
References: