Functional Dyspepsia Treatment Trial

Condition(s) targeted: Functional Dyspepsia

Intervention: Amitriptyline (Drug); escitalopram (Drug); placebo (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Earnest P Bouras, M.D., Principal Investigator, Affiliation: Mayo Clinic
John K. DiBaise, M.D., Principal Investigator, Affiliation: Mayo Clinic Scottsdale
Michael P Jones, M.D., Principal Investigator, Affiliation: Northwestern Memorial Hospital
Charlene M Prather, M.D., Principal Investigator, Affiliation: St. Louis University
Nicholas J Talley, M.D.,Ph.D., Principal Investigator, Affiliation: Mayo Clinic
Brian E. Lacy, M.D., Ph.D., Principal Investigator, Affiliation: Dartmouth-Hitchcock Medical Center
G. R. Locke, III, M.D., Principal Investigator, Affiliation: Mayo Clinic
Bincy P Abraham, M.D., M.S., Principal Investigator, Affiliation: Baylor College of Medicine

Overall contact:
Vickie M Silvernail, LPN, CCRP, Phone: 507-284, Ext: 2812, Email: silvernail.vickie@mayo.edu

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.

Official title: Antidepressant Therapy for Functional Dyspepsia

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

Primary outcome: Assess whether antidepressant therapy is more efficacious than placebo in relief of the symptoms of functional dyspepsia, adjusting for psychological and psychiatric co-morbidity.

Secondary outcome:

Assess whether gastric emptying and the nutrient drink test is altered by therapy with a tricyclic or SSRI antidepressant.

Examine whether polymorphisms of the heterotrimeric G protein and serotonin reuptake transporter predict outcome in functional dyspepsia patients receiving antidepressant therapy.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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.

Vickie M Silvernail, LPN, CCRP, Phone: 507-284, Ext: 2812, Email: silvernail.vickie@mayo.edu

Mayo Clinic, Scottsdale, Arizona 85259, United States; Recruiting
Machiko (Tina) H. Anderson, Phone: 480-301-8000, Ext: 2-7056, Email: anderson.machiko@mayo.edu
John K. Dibaise, M.D., Principal Investigator
Michael D. Crowell, Ph.D., Sub-Investigator

Mayo Clinic Jacksonville, Jacksonville, Florida 32224, United States; Recruiting
Verna Skinner, Phone: 904-953-2000, Ext: 3-2255, Email: skinner.verna@mayo.edu
Earnest P Bouras, M.D., Principal Investigator

Northwestern University, Chicago, Illinois 60611, United States; Recruiting
Michael P. Jones, M.D., Phone: 312-695-4054
Jason R Bratten, Phone: 312-695-2742, Email: j-bratten@northwestern.edu
Michael P Jones, M.D., Principal Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Vickie M Silvernail, L.P.N., Phone: 507-284-2511, Ext: 2812, Email: silvernail.vickie@mayo.edu
Linda M Herrick, Ph.D., Phone: 507-284-2511, Email: herrick.linda@mayo.edu
Nicholas J Talley, M.D.,Ph.D., Principal Investigator
G. R. Locke, III, M.D., Sub-Investigator

Saint Louis University School od Medicine, Saint Louis, Missouri 63130, United States; Recruiting
Charlene M. Prather, M.D., Phone: 314-577-8764, Email: pratherc@slu.edu
Debra King, R.N., Phone: 314-977-9320, Email: kingdl@slu.edu
Charlene M Prather, M.D., Principal Investigator

Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Recruiting
Brian E. Lacy, M.D., Ph.D., Phone: 603-650-5215
Carol A. Moriarty, R.N., Phone: 603-653-3665, Email: carol.a.moriarty@hitchcock.org
Brian E. Lacy, M.D., Principal Investigator

Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Bincy P Abraham, M.D., M.S., Phone: 713-798-0950, Email: bincya@bcm.tmc.edu
Sara A. Raymon, BA/CCRP, Phone: 713-798-7616, Email: raymon@bcm.tmc.edu
Bincy P. Abraham, M.D., M.S., Principal Investigator

Starting date: October 2006
Ending date: December 2011
Last updated: September 22, 2009