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Functional DyspepsiaPhase 3TENDERNCT03652571

Nortriptyline for the Treatment of Functional Dyspepsia

A Phase 3 study testing Nortriptyline in people with Functional Dyspepsia, run by Maastricht University Medical Center at 14 sites in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Functional Dyspepsia
What is being tested?
Nortriptyline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
96 participants
Where
14 sitesNetherlands
Study dates
1 Sep 2018to 1 Aug 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 14Show fewer
  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Netherlands14 sites

  • Jeroen Bosch ziekenhuis

    's-Hertogenbosch

  • AMC

    Amsterdam

  • VUmc

    Amsterdam

  • Rijnstate

    Arnhem

  • Gelderse Vallei

    Ede

  • Medisch Spectrum Twente

    Enschede

  • Martini Ziekenhuis

    Groningen

  • Tergooi Hilversum

    Hilversum

  • Medisch Centrum Leeuwarden

    Leeuwarden

  • Alrijne ziekenhuis

    Leiden

  • Maastrich University Medical Center

    Maastricht

  • Bernhoven

    Uden

  • Diakonessenhuis

    Utrecht

  • MMC

    Veldhoven

Other trials in Netherlands

About this study

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

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.

Being tested
Nortriptyline, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NortriptylineDrug

    Nortriptyline escalating dose regimen:

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

  • PlaceboDrug

    Placebo

Study groups in NCT03652571
Study groupRoleWhat they receive
NortriptylineExperimentalNortriptyline in an escalating dose regimen: Week 1-2: 10mg daily Week 3-4: 25mg daily Week 5-12: 50mg daily
Receives: Drug: Nortriptyline
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 weeks

Secondary outcomes (9)

  1. 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)

    Measured: 12 weeks

  2. General quality of life

    Assessed with the use of the Euro-Qol-5D (EQ-5D; change from baseline).

    Measured: 12 weeks, 3 & 6 months

  3. Dyspepsia-specific quality of life

    Dyspepsia-specific quality of life, assessed with the use of the Nepean Dyspepsia Index (NDI; change from baseline).

    Measured: 12 weeks, 3 & 6 months

  4. 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].

    Measured: 12 weeks, 3 & 6 months

  5. Use of rescue medication.

    As reported via digital diary (mobile phone application)

    Measured: 12 weeks

  6. Number and severity of side effects.

    As reported via digital diary (mobile phone application)

    Measured: 12 weeks

  7. 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.

    Measured: 6 months

  8. Negative mood - anxiety

    Assessed with the use of the Generalized Anxiety Disorder-7 (GAD-7; change from baseline)

    Measured: 12 weeks, 3 & 6 months

  9. Negative mood - depression

    Assessed with the use of the Patient Health Questionnaire-9 (PHQ-9; change from baseline)

    Measured: 12 weeks, 3 & 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2018
  2. Study start1 Sep 2018
  3. Primary completion1 Aug 2024
  4. Study completion1 Aug 2024

Why it stopped: The inclusion of participants went more difficult than initially thought. Preliminary analysis showed that the difference between the groups was great enough to draw conclusions from it, so the trial is terminated prematurely.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03652571
Sponsor's protocol ID
848016005
Other IDs
NL62932.068.17 / METC173051, 2017-003307-21, 2017
Acronym
TENDER
Status last verified
Aug 2018
First submitted
17 Aug 2018
Last updated
3 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bosch DHCA, Essers BAB, Beckers AB, Snijkers JTW, Winkens B, Masclee AAM, Keszthelyi D. Characterising the Economic Burden of Functional Dyspepsia: A Cost-of-Illness Study of Direct and Indirect Costs. United European Gastroenterol J. 2026 Sep;14(7):e70257. doi: 10.1002/ueg2.70257.

    PubMed 42530136

  • Bosch DHCA, Beckers AB, Snijkers JTW, Bosman MHMA, Winkens B, Muris JWM, de Wit N, Brouwers JRBJ, van Hee K, Clemens CHM, Haarhuis BJT, Witteman BJM, Masclee AAM, Keszthelyi D. Tailored Treatment of Functional Dyspepsia With Nortriptyline: A Multicenter, Double-Blind, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2026 Aug;24(8):2273-2285. doi: 10.1016/j.cgh.2026.01.013. Epub 2026 Jan 29.

    PubMed 41616902

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nortriptyline in people with Functional Dyspepsia, run by Maastricht University Medical Center at 14 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The inclusion of participants went more difficult than initially thought. Preliminary analysis showed that the difference between the groups was great enough to draw conclusions from it, so the trial is terminated prematurely.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Symptom response (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03652571, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.

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