Nortriptyline for the Treatment of Functional Dyspepsia

Functional Dyspepsia Clinical Trial

— TENDER  

Official title:

Tailored Treatment of Functional Dyspepsia With Nortriptyline: a Multi-center Double-blind Placebo-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03652571
• Other study ID #: 848016005
• Secondary ID: NL62932.068.17 /
• Status: Recruiting
• Phase: Phase 3
• Start date: September 1, 2018
• Est. completion date: September 1, 2021

Study information

• Verified date: August 2018
• Source: Maastricht University Medical Center
• Contact: Bram Beckers, MD
• Phone: 0031 43 388 1844
• Email: tender-intmed[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 154
• Est. completion date: September 1, 2021
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyspepsia
• Functional Dyspepsia
• Gastritis

Intervention

Drug:
• Nortriptyline
Nortriptyline escalating dose regimen: Week 1-2: 10mg Week 3-4: 25mg Week 5-12: 50mg
• Placebo
Placebo

Locations

Country	Name	City	State
Netherlands	AMC	Amsterdam
Netherlands	VUmc	Amsterdam
Netherlands	Rijnstate	Arnhem
Netherlands	Jeroen Bosch ziekenhuis	Den Bosch
Netherlands	Gelderse Vallei	Ede
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Tergooi Hilversum	Hilversum
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Alrijne ziekenhuis	Leiden
Netherlands	Maastrich University Medical Center	Maastricht
Netherlands	Bernhoven	Uden
Netherlands	Diakonessenhuis	Utrecht
Netherlands	MMC	Veldhoven

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Symptom response	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.	12 weeks
Secondary	Adequate relief	Self-reported adequate relief. Adequate relief is defined as a 'yes' response in at least 50% of weeks 3-12 of the treatment. Reported via digital diary (mobile phone application)	12 weeks
Secondary	General quality of life	Assessed with the use of the Euro-Qol-5D (EQ-5D; change from baseline).	12 weeks, 3 & 6 months
Secondary	Dyspepsia-specific quality of life	Dyspepsia-specific quality of life, assessed with the use of the Nepean Dyspepsia Index (NDI; change from baseline).	12 weeks, 3 & 6 months
Secondary	Cost-utility	Cost-utility, as determined by calculations incorporating total treatment costs and changes in EQ-5D-5L (QALYs gained), and results from the Medical Consumption Questionnaire (MCQ) and Productivity Cost Questionnaire (PCQ) [savings from reduced medical resource use and increased work productivity respectively].	12 weeks, 3 & 6 months
Secondary	Use of rescue medication.	As reported via digital diary (mobile phone application)	12 weeks
Secondary	Number and severity of side effects.	As reported via digital diary (mobile phone application)	12 weeks
Secondary	Responder rates following discontinuation	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.	6 months
Secondary	Negative mood - anxiety	Assessed with the use of the Generalized Anxiety Disorder-7 (GAD-7; change from baseline)	12 weeks, 3 & 6 months
Secondary	Negative mood - depression	Assessed with the use of the Patient Health Questionnaire-9 (PHQ-9; change from baseline)	12 weeks, 3 & 6 months