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

Condition(s) targeted: Dyspepsia

Intervention: Imipramine (Drug); placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Chinese University of Hong Kong

Official(s) and/or principal investigator(s):
Justin C Wu, MD, Principal Investigator, Affiliation: Chinese University of Hong Kong

Overall contact:
Justin C Wu, MD, Phone: 85226323024, Email: justinwu@cuhk.edu.hk

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.

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Primary Outcome: Overall satisfactory relief (GSA) at 12 weeks

Secondary outcome: Individual dyspepsia symptom scores Days of sleep disturbance SODA score Response in different subtypes of dyspepsia

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients fulfill the diagnostic criteria of functional dyspepsia as defined by Rome II

criteria.

- Age >18

- Failure of treatment response to PPI, H2 receptor antagonist, 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

Justin C Wu, MD, Phone: 85226323024, Email: justinwu@cuhk.edu.hk

Endoscopy Center, Prince of Wales Hospital, Hong Kong, China; Recruiting
Justin C Wu, MD, Phone: 85226323024, Email: justinwu@cuhk.edu.hk
Jessica P Cheong, Dip, Phone: 85226323855, Email: jessicacheong@cuhk.edu.hk
Justin C Wu, MD, Principal Investigator

Starting date: June 2005
Last updated: March 21, 2008