Official Title: “Antidepressant Therapy for Functional Dyspepsia”

We propose to investigate whether antidepressant medications are efficacious in functional dyspepsia. The prescription of antidepressants to treat functional dyspepsia is based on three propositions. First, antidepressants could reduce the severity of co-morbid psychological symptoms, especially anxiety and depression. Second, antidepressants have central analgesic actions. Thirdly, antidepressants have been shown to have local pharmacological actions on the gut, and may specifically alter gastric emptying and fundic relaxation based on preliminary data, but the relevance of such pertubations to treatment outcome is not established.

Study Type: Interventional

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

Study Primary Completion Date: December 2010

In a parallel group, double blind, randomized, placebo-controlled adequately powered three-arm,multi-center trial, the aims of the present study are to:

1. Determine whether antidepressant therapy is more efficacious than placebo in relief of the symptoms of functional dyspepsia, adjusting for psychological and psychiatric co-morbidity. We will also determine if antidepressant therapy reduces disability, improves quality of life and influences clinical response over 6 months after ceasing medication.

2. Determine if gastric emptying (motor dysfunction) and the nutrient drink test (a test that assesses gastric hypersensitivity and/or gastric accommodation) is altered by antidepressant therapy with a tricyclic or SSRI, and whether subgroups with altered physiology are associated with treatment outcome. In a sub-study, we will directly determine if impaired gastric accommodation (by a novel validated non-invasive imaging method using 99mTc-SPECT) and the symptom response to a nutrient drink test is altered by an SSRI or tricyclic antidepressant.

3. Determine if polymorphisms of GNβ3 and the serotonin reuptake transporter predict outcome in functional dyspepsia patients receiving a tricyclic antidepressant or SSRI therapy.

Intervention(s) in this Clinical Trial

• Drug: Amitriptyline
  • 25mg by mouth at bedtime for two weeks, then 50 mg by mouth at bedtime for 10 weeks.
• Drug: escitalopram
  • 10mg by mouth at bedtime for 12 weeks
• Drug: placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • amitriptyline
• Active Comparator: 2
  • escitalopram
• Placebo Comparator: 3

Primary Measures

• Assess whether antidepressant therapy is more efficacious than placebo in relief of the symptoms of functional dyspepsia, adjusting for psychological and psychiatric co-morbidity.
  • Time Frame: end of study
    Safety Issue?: No

Secondary Measures

• Assess whether gastric emptying and the nutrient drink test is altered by therapy with a tricyclic or SSRI antidepressant.
  • Time Frame: end of study
    Safety Issue?: No
• Examine whether polymorphisms of the heterotrimeric G protein and serotonin reuptake transporter predict outcome in functional dyspepsia patients receiving antidepressant therapy.
  • Time Frame: end of study
    Safety Issue?: No

Inclusion Criteria:

• Patients will have had in the prior 5 year, a normal esophagogastroduodenoscopy (EGD) (no esophagitis, Barrett's esophagus, cancer, erosions, or ulcer disease), and will have been diagnosed with functional dyspepsia after specialist consultation.
• Patients will have failed to adequately respond to antisecretory therapy in the past for functional dyspepsia to be suitable; a good response to antisecretory therapy, which remains first line therapy, suggests underlying GERD (8).

Exclusion Criteria:

• Any documented history of endoscopic esophagitis, or predominant heartburn or acid regurgitation, or these symptoms two or more times per week in the prior year, to exclude GERD.
• Those who have had an adequate response to antisecretory therapy according to the physician interview, to exclude patients with disease easy to control with first line therapy or misdiagnosed GERD.
• Any documented peptic ulcer disease.
• Regular use of non-steroidal anti-inflammatory drugs (except long term low dose aspirin).
• Subjects undergoing psychiatric treatment, having a history of drug or alcohol abuse, or currently taking psychotropic medication (psychiatric diagnoses will not be an exclusion, except for psychosis).
• A history of abdominal surgery except appendectomy, cholecystectomy or hysterectomy more than one year previously.
• Subjects with concurrent major physical illness (including cardiac or liver disease, diabetes, inflammatory bowel disease, glaucoma, urinary retention, active thyroid disease, vasculitis, lactose intolerance explaining symptoms), psychotic illness or eating disorder.
• Subjects whose literacy skills are insufficient to complete self report questionnaires.
• Pregnancy, or refusal to apply adequate contraceptive measures during the trial.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Overall Clinical Trial Officials and Contacts

Earnest P Bouras, M.D. Principal Investigator Mayo Clinic  

Overall Contact: Vickie M Silvernail, LPN, CCRP 507-284 silvernail.vickie@mayo.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00248651

Study ID Number: 2021-05

ClinicalTrials.gov Identifier: NCT00248651

Health Authority: United States: Federal Government