Nortriptyline for the Treatment of Functional Dyspepsia

NCT03652571 | Terminated Phase 3 DMC

• 3 other identifiers: 848016005NL62932.068.17 / METC1730512017-003307-21
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 14

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Adequate relief

  12 weeks

• General quality of life

  12 weeks, 3 & 6 months

• Dyspepsia-specific quality of life

  12 weeks, 3 & 6 months

• Cost-utility

  12 weeks, 3 & 6 months

• Use of rescue medication.

  12 weeks

Study Arms (2)

Nortriptyline

EXPERIMENTAL

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

Drug: Nortriptyline

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Nortriptyline DRUG

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

Nortriptyline

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Women in their fertile age (\<55 years old) must use contraception or be postmenopausal for at least two years.

You may not qualify if:

• 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;
• 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:
• Uncomplicated appendectomy, cholecystectomy and hysterectomy allowed unless within the past 6 months;
• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (14)

Jeroen Bosch ziekenhuis

's-Hertogenbosch, Netherlands

Location

AMC

Amsterdam, Netherlands

Location

VUmc

Amsterdam, Netherlands

Location

Rijnstate

Arnhem, Netherlands

Location

Gelderse Vallei

Ede, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Martini Ziekenhuis

Groningen, Netherlands

Location

Tergooi Hilversum

Hilversum, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Alrijne ziekenhuis

Leiden, Netherlands

Location

Maastrich University Medical Center

Maastricht, Netherlands

Location

Bernhoven

Uden, Netherlands

Location

Diakonessenhuis

Utrecht, Netherlands

Location

MMC

Veldhoven, Netherlands

Location

Related Publications (1)

• Bosch DH, Beckers AB, Snijkers JTW, Bosman MH, Winkens B, Muris JWM, de Wit N, Brouwers JR, van Hee K, Clemens CHM, Haarhuis BJT, Witteman BJM, Masclee AAM, Keszthelyi D. Tailored treatment of functional dyspepsia with nortriptyline: a multi-center, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2026 Jan 28:S1542-3565(26)00041-8. doi: 10.1016/j.cgh.2026.01.013. Online ahead of print.

  PMID: 41616902 DERIVED

MeSH Terms

Interventions

Nortriptyline

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Ad A.A.M Masclee, Prof

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2018
• First Posted: August 29, 2018
• Study Start: September 1, 2018
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: July 3, 2025

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (14)