Nortriptyline for the Treatment of Functional Dyspepsia

NCT ID: NCT03652571

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2024-08-01

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.

Conditions

Functional Dyspepsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nortriptyline

Nortriptyline in an escalating dose regimen:

Week 1-2: 10mg daily Week 3-4: 25mg daily Week 5-12: 50mg daily

Group Type: EXPERIMENTAL

Nortriptyline

Intervention Type: DRUG

Nortriptyline escalating dose regimen:

Week 1-2: 10mg Week 3-4: 25mg Week 5-12: 50mg

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Nortriptyline

Nortriptyline escalating dose regimen:

Week 1-2: 10mg Week 3-4: 25mg Week 5-12: 50mg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ad A.A.M Masclee, Prof

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Jeroen Bosch ziekenhuis

's-Hertogenbosch, , Netherlands

AMC

Amsterdam, , Netherlands

VUmc

Amsterdam, , Netherlands

Rijnstate

Arnhem, , 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, , Netherlands

Countries

Netherlands

Other Identifiers

NL62932.068.17 / METC173051

Identifier Type: OTHER

Identifier Source: secondary_id

2017-003307-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

848016005

Identifier Type: -

Identifier Source: org_study_id