The Efficacy of Imipramine in Treatment of Refractory Functional Dyspepsia

NCT ID: NCT00164775

Last Updated: 2016-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2010-08-31

Brief Summary

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

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.

Conditions

Functional Gastrointestinal Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Imipramine

Imipramine 25mg nocte for first 2 weeks then Imipramine 50 mg nocte for 10 weeks

Group Type: ACTIVE_COMPARATOR

Imipramine

Intervention Type: DRUG

25mg nocte for first 2 weeks then 50 mg nocte for 10 weeks

Placebo

Placebo 1 tablet for first 2 weeks then Placebo 2 tablets for 10 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One tab nocte for first 2 weeks then 2 tabs for 10 weeks

Interventions

Imipramine

25mg nocte for first 2 weeks then 50 mg nocte for 10 weeks

Intervention Type: DRUG

Placebo

One tab nocte for first 2 weeks then 2 tabs for 10 weeks

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Justin Che-Yuen Wu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Justin CY Wu, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Countries

Hong Kong

References

Cheong PK, Ford AC, Cheung CKY, Ching JYL, Chan Y, Sung JJY, Chan FKL, Wu JCY. Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2018 Dec;3(12):837-844. doi: 10.1016/S2468-1253(18)30303-0. Epub 2018 Oct 22.

Reference Type: DERIVED

PMID: 30361080 (View on PubMed)

Other Identifiers

DA Study

Identifier Type: -

Identifier Source: org_study_id