Nortriptyline for the Treatment of Functional Dyspepsia (TENDER)

Maastricht University Medical Centre (MUMC)

Status and phase: Terminated; Phase 3

Conditions: Functional Dyspepsia

Treatments: Drug: Nortriptyline; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03652571

848016005

NL62932.068.17 / METC173051 (Other Identifier)

2017-003307-21 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 96 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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96 participants in 2 patient groups, including a placebo group

Nortriptyline

Experimental group

Description:

Nortriptyline in an escalating dose regimen: Week 1-2: 10mg daily Week 3-4: 25mg daily Week 5-12: 50mg daily

Treatment:

Drug: Nortriptyline

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo