The Efficacy of Imipramine in Treatment of Refractory Functional Dyspepsia

Study Overview
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Brief Summary
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The aim of this study is evaluate the efficacy of Imipramine, a tricyclic antidepressant, in treatment of functional dyspepsia. This is a double blind randomised placebo controlled trial in which consecutive patients with diagnosis of functional dyspepsia will be studied. After exclusion of organic cause of dyspepsia by endoscopy, these patients will be randomly assigned to either imipramine or placebo. All the patients will enter an additional 4 weeks of drug withdrawal phase after the initial 12 weeks of study drug treatment. They will be evaluated for treatment response, which is defined as satisfactory relief of dyspeptic symptoms at the end of 12-week treatment.

Detailed Description
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Functional dyspepsia is a heterogeneous disorder that consists of a variety of upper gastrointestinal symptoms such as postprandial fullness, early satiety, pain, bloating, belching, or nausea. The pathophysiology of functional dyspepsia is not fully understood and the correlation of those proposed mechanisms with the clinical characteristics and treatment response is poor. Owing to the poor understanding on the mechanism, treatment of functional dyspepsia has been far from satisfactory. There are numerous modalities of medical treatment that has been reported to be effective but the results are conflicting. Large and well-controlled studies in functional dyspepsia have shown that proton pump inhibitor had a therapeutic gain of about 10%-15% better than placebo in patients with functional dyspepsia. However, this positive effect was restricted to patients with reflux-like dyspepsia, a subgroup that actually is no longer considered to belong to functional dyspepsia. Prokinetic agent is another class of drug that has been widely used in functional dyspepsia. Although recent reviews suggest that prokinetics are more effective than placebo, most trials were flawed with significant heterogeneity among studies. Tricyclic antidepressant (TCA) is another important class of drug that is commonly used in various functional gastrointestinal disorders (FGID) and chronic pain disorders. The effectiveness of TCA in FGID has been supported by a meta-analysis, which reported that improvement in global GI symptoms against placebo was highly significant. The mechanism of TCA in treatment of FGID is poorly understood but the therapeutic effect is evident even in low dose, suggesting that it is independent of its anti-depressive action. To date, clinical trial of TCA in treatment of FD with sufficient sample size and well-defined clinical endpoint is still lacking. So the objective of this study is to evaluate the efficacy of imipramine, a tricyclic antidepressant, in treatment of functional dyspepsia.

Official Title
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The Efficacy of Imipramine in Treatment of Functional Dyspepsia: A Double Blind Randomized Placebo Controlled Trial

Conditions
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Functional Gastrointestinal Disorder

Intervention / Treatment
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* Drug: Imipramine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fulfill the diagnostic criteria of functional dyspepsia as defined by Rome II criteria Age > 18 years old Failure of treatment response to PPI, H2 receptor antagonist fo 8 weeks and domperidone for 4 weeks Exclusion Criteria: Organic pathology detected by endoscopy GERD or IBS as dominant compliant Presence of any alarm symptom: anemia, recurrent vomiting, weight loss Concomitant Helicobacter pylori infection Concomitant use of neuroleptic or antidepressant, NSAID Previous gastrointestinal surgery Cardiac arrhythmia, untreated glaucoma or benign prostate hypertrophy Pregnancy Known hypersensitivity or contraindication for tricyclic antidepressant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imipramine<br>Imipramine 25mg nocte for first 2 weeks then Imipramine 50 mg nocte for 10 weeks | Drug: Imipramine<br>* 25mg nocte for first 2 weeks then 50 mg nocte for 10 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo 1 tablet for first 2 weeks then Placebo 2 tablets for 10 weeks | Drug: Placebo<br>* One tab nocte for first 2 weeks then 2 tabs for 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall satisfactory relief (Global Symptom Assessment) at 12 weeks | It is defined as a response of Yes to the question: Do you experience overall satisfactory relief of dyspeptic symptom with the current treatment? by global symptom assessment. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual dyspeptic symptom scores | 8-item dyspepsia symptom score questionnaire assessing epigastric pain, epigastric burning, postprandial fullness, early satiety, belching, bloating, nausea, and vomiting on a scale of 0-3 over the last 7 days | 12 weeks | 
| Days of sleep disturbance | Effect on sleep will be assessed by asking patients if they had insomnia on ≥1 day per week | 12 weeks | 
| Mood assessment | Effect on mood will be assessed using the hospital anxiety and depression scale (HADS) | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional dyspepsia, refractory, antidepressant