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Nortriptyline for the Treatment of Functional Dyspepsia (TENDER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03652571
Recruitment Status : Unknown
Verified August 2018 by Maastricht University Medical Center.
Recruitment status was:  Recruiting
First Posted : August 29, 2018
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Functional Dyspepsia Drug: Nortriptyline Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tailored Treatment of Functional Dyspepsia With Nortriptyline: a Multi-center Double-blind Placebo-controlled Trial
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Indigestion

Arms and Interventions
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Arm Intervention/treatment
Experimental: Nortriptyline

Nortriptyline in an escalating dose regimen:

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

 Drug: Nortriptyline

Nortriptyline escalating dose regimen:

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


Outcome Measures
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Primary Outcome Measures :
  1. Symptom response [ Time Frame: 12 weeks ]
    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.


Secondary Outcome Measures :
  1. Adequate relief [ Time Frame: 12 weeks ]
    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)

  2. General quality of life [ Time Frame: 12 weeks, 3 & 6 months ]
    Assessed with the use of the Euro-Qol-5D (EQ-5D; change from baseline).

  3. Dyspepsia-specific quality of life [ Time Frame: 12 weeks, 3 & 6 months ]
    Dyspepsia-specific quality of life, assessed with the use of the Nepean Dyspepsia Index (NDI; change from baseline).

  4. Cost-utility [ Time Frame: 12 weeks, 3 & 6 months ]
    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].

  5. Use of rescue medication. [ Time Frame: 12 weeks ]
    As reported via digital diary (mobile phone application)

  6. Number and severity of side effects. [ Time Frame: 12 weeks ]
    As reported via digital diary (mobile phone application)

  7. Responder rates following discontinuation [ Time Frame: 6 months ]
    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.

  8. Negative mood - anxiety [ Time Frame: 12 weeks, 3 & 6 months ]
    Assessed with the use of the Generalized Anxiety Disorder-7 (GAD-7; change from baseline)

  9. Negative mood - depression [ Time Frame: 12 weeks, 3 & 6 months ]
    Assessed with the use of the Patient Health Questionnaire-9 (PHQ-9; change from baseline)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652571


Contacts
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Contact: Bram Beckers, MD 0031 43 388 1844 tender-intmed@maastrichtuniversity.nl
Contact: Daniel Keszthelyi, MD, PhD daniel.keszthelyi@maastrichtuniversity.nl

Locations
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Netherlands
AMC Not yet recruiting
Amsterdam, Netherlands
Contact: A.J. Bredenoord         
VUmc Not yet recruiting
Amsterdam, Netherlands
Contact: R.J.F Felt-Bersma         
Rijnstate Not yet recruiting
Arnhem, Netherlands
Contact: D.P. Hirsch         
Jeroen Bosch ziekenhuis Not yet recruiting
Den Bosch, Netherlands
Contact: K van Hee         
Gelderse Vallei Not yet recruiting
Ede, Netherlands
Contact: B.J.M Witteman         
Medisch Spectrum Twente Not yet recruiting
Enschede, Netherlands
Contact: J.J. Kolkman         
Martini Ziekenhuis Not yet recruiting
Groningen, Netherlands
Contact: L.A. van der Waaij         
Tergooi Hilversum Not yet recruiting
Hilversum, Netherlands
Contact: B.D.J. van den Elzen         
Medisch Centrum Leeuwarden Not yet recruiting
Leeuwarden, Netherlands
Contact: H.J.A. Jebbink         
Alrijne ziekenhuis Not yet recruiting
Leiden, Netherlands
Contact: C.H.M. Clemens         
Maastrich University Medical Center Recruiting
Maastricht, Netherlands
Contact: Daniel Keszthelyi         
Bernhoven Not yet recruiting
Uden, Netherlands
Contact: B.J.T. Haarhuis         
Diakonessenhuis Not yet recruiting
Utrecht, Netherlands
Contact: A.H. Oberndorff-Klein Woolthuis         
MMC Not yet recruiting
Veldhoven, Netherlands
Contact: J.W.A. Straathof         
Sponsors and Collaborators
Maastricht University Medical Center
Investigators
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Principal Investigator: Ad A.A.M Masclee, Prof Maastricht University Medical Center
More Information
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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT03652571    
Other Study ID Numbers: 848016005
NL62932.068.17 / METC173051 ( Other Identifier: METC azM/UM )
2017-003307-21 ( EudraCT Number )
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Dyspepsia
Signs and Symptoms, Digestive
Nortriptyline
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Adrenergic Uptake Inhibitors
 Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs