Clinical trial NCT00248651: Functional Dyspepsia Treatment Trial
Official title: Antidepressant Therapy for Functional Dyspepsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dyspepsia and Other Specified Disorders of Function of Stomach
Keywords: Bloating
Early Fullness
Nausea
Upper Abdominal Discomfort
dyspepsia
stomach pain
stomach discomfort
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2005-11-04
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Functional dyspepsia is a common gastrointestinal disorder. Symptoms can include stomach pain or discomfort, bloating, fullness after eating meals, and nausea. These symptoms often interfere with school and work, and weight loss may occur due to dietary restrictions.

The hypothesis of this study was that antidepressant therapy is more effective than placebo in relief of the symptoms of functional dyspepsia, adjusting for psychological and psychiatric co-morbidity. The study also examined if antidepressant therapy reduces disability and improves quality of life in functional dyspepsia.

Detailed description: The aims of this study were 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. The investigators also planned to 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 selective serotonin re-uptake inhibitors (SSRI), and whether subgroups with altered physiology are associated with treatment outcome.

Eligibility criteria: Inclusion Criteria:

* Normal esophagogastroduodenoscopy (EGD) (no esophagitis, Barrett's esophagus, cancer, erosions, or ulcer disease) within the past 5 years
* Diagnosis of functional dyspepsia
* Patients may 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 gastroesophageal reflux disease (GERD).

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 ≤ 325 mg / day)
* Subjects undergoing psychiatric treatment, having a current history of drug or alcohol abuse, or currently taking psychotropic medication for depression or psychosis, or eating disorders
* A history of abdominal surgery except appendectomy, cholecystectomy or hysterectomy, tubal ligations, bladder slings, and vasectomies
* 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)
* Subjects whose literacy skills are insufficient to complete self report questionnaires.
* Pregnancy, or refusal to apply adequate contraceptive measures during the trial
* Subjects currently on antidepressant therapy will be excluded.
* Patients who score 11 or greater on the 7 questions related to depression of the Hospital Anxiety Depression Scale will be excluded. These patients will be encouraged to get follow up for depression.
* All eligible patients over age 50 will have an EKG before randomization. Those found to have significant arrhythmias, conduction defects or a previous myocardial infarction on EKG will be excluded. Anyone with QT prolongation will be excluded.

The following concomitant medications will be prohibited during the trial:

* Systemically acting cholinergics and anticholinergics (atropine, didinium bromide, propantheline)
* Prokinetics (e.g., metoclopramide, tegaserod)
* Macrolide antibiotics (e.g., erythromycin, azithromycin)
* Aspirin (\> 325 mg/day)
* Spasmolytics (e.g., dicyclomine)
* Antidepressants other than study medications
* Serotonin enhancing drugs: monamine oxidase inhibitors, anticonvulsants, dextromethorphan.

Participants will be instructed to avoid grapefruit/grapefruit juice during the trial.

Primary outcomes:
measure: Self-Report of Adequate Relief of Dyspepsia (Yes/No) For at Least 50% of Weeks 3 -12 of Treatment
timeFrame: 3 weeks through 12 weeks
Secondary outcomes:
measure: Gastric Emptying Half-Time (T1/2)
timeFrame: 12 weeks
measure: Maximum Tolerated Volume by Nutrient Drink Test
timeFrame: 12 weeks
measure: Dyspepsia-Specific Quality of Life
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern University Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Hamilton
country: Canada
facility: McMaster University Centre
state: Ontario
Study officials:
affiliation: Mayo Clinic
name: Earnest P Bouras, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: John K. DiBaise, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University Chicago
name: Colin P Howden, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Louis University
name: Charlene M Prather, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Nicholas J Talley, M.D.,Ph.D.
role: STUDY_CHAIR
affiliation: Dartmouth-Hitchcock Medical Center
name: Brian E. Lacy, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: G. R. Locke, III, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Bincy P Abraham, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Hashem El-Serag, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University Centre, Hamilton, Ontario
name: Paul Moayyedi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herrick LM, Camilleri M, Schleck CD, Zinsmeister AR, Saito YA, Talley NJ. Effects of Amitriptyline and Escitalopram on Sleep and Mood in Patients With Functional Dyspepsia. Clin Gastroenterol Hepatol. 2018 Mar;16(3):401-406.e2. doi: 10.1016/j.cgh.2017.10.021. Epub 2017 Dec 1.
citation: Talley NJ, Locke GR, Saito YA, Almazar AE, Bouras EP, Howden CW, Lacy BE, DiBaise JK, Prather CM, Abraham BP, El-Serag HB, Moayyedi P, Herrick LM, Szarka LA, Camilleri M, Hamilton FA, Schleck CD, Tilkes KE, Zinsmeister AR. Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study. Gastroenterology. 2015 Aug;149(2):340-9.e2. doi: 10.1053/j.gastro.2015.04.020. Epub 2015 Apr 25.
citation: Herrick LM, Locke GR 3rd, Schleck CD, Zinsmeister AR, Treder V, Talley NJ. Dyspepsia in the community: value of a community-based mailed survey to identify potential participants for a randomized clinical trial. Scand J Gastroenterol. 2015 Aug;50(8):959-64. doi: 10.3109/00365521.2014.980317. Epub 2015 Mar 11.
citation: Talley NJ, Locke GR 3rd, Herrick LM, Silvernail VM, Prather CM, Lacy BE, DiBaise JK, Howden CW, Brenner DM, Bouras EP, El-Serag HB, Abraham BP, Moayyedi P, Zinsmeister AR. Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics. Contemp Clin Trials. 2012 May;33(3):523-33. doi: 10.1016/j.cct.2012.02.002. Epub 2012 Feb 10.