Functional Dyspepsia Treatment Trial

NCT00248651 | Completed Phase 2 Results DMC

• 2 other identifiers: 2021-05 (DK065713)U01DK065713
• Study Type: interventional
• Target: 292
• Locations: 2 countries
• Sites: 8

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.

Conditions

Dyspepsia and Other Specified Disorders of Function of Stomach

Keywords

Bloating; Early Fullness; Nausea; Upper Abdominal Discomfort; dyspepsia; stomach pain; stomach discomfort

Outcome Measures

Primary Outcomes (1)

• Self-Report of Adequate Relief of Dyspepsia (Yes/No) For at Least 50% of Weeks 3 -12 of Treatment

  The first two weeks of treatment were excluded to allow for establishment of steady state drug levels.

  3 weeks through 12 weeks

Secondary Outcomes (3)

• Gastric Emptying Half-Time (T1/2)

  12 weeks

• Maximum Tolerated Volume by Nutrient Drink Test

  12 weeks

• Dyspepsia-Specific Quality of Life

  12 Weeks

Study Arms (3)

Amitriptyline

ACTIVE COMPARATOR

Amitriptyline capsule (50 mg) plus a placebo escitalopram tablet will be taken at night half an hour before bedtime. To maximize patient tolerability, in the first 2 weeks the dose of amitriptyline will be 25 mg and then the dose will be increased to 50 mg, but the 25 mg and 50 mg capsules will be indistinguishable to maintain blinding.

Drug: Amitriptyline

Escitalopram

ACTIVE COMPARATOR

Escitalopram tablet (10 mg) plus a placebo amitriptyline capsule will be taken by mouth at night half an hour before bedtime for 12 weeks.

Drug: Escitalopram

Placebo

PLACEBO COMPARATOR

Placebo escitalopram tablets and placebo amitriptyline capsules will be taken by mouth half an hour before bedtime for 12 weeks.

Drug: Placebo

Interventions

Amitriptyline DRUG

25 mg capsule by mouth at bedtime for two weeks, then 50 mg capsule by mouth at bedtime for 10 weeks. The drug will be provided in blister packs.

Also known as: Elavil

Amitriptyline

Escitalopram DRUG

10 mg tablets by mouth at bedtime for 12 weeks. The drug will be provided in blister packs.

Also known as: Lexapro

Escitalopram

Placebo DRUG

Placebo escitalopram and placebo amitriptyline will be manufactured to ensure all tablets and capsules will be indistinguishable, and provided in blister packs.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (8)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern University Chicago

Chicago, Illinois, 60611, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Louis University School of Medicine

St Louis, Missouri, 63130, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

McMaster University Centre

Hamilton, Ontario, Canada

Location

Related Publications (4)

• 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.

  PMID: 29199141 DERIVED

• 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.

  PMID: 25921377 DERIVED

• 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.

  PMID: 25761431 DERIVED

• 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.

  PMID: 22343090 DERIVED

MeSH Terms

Conditions

Dyspepsia; Nausea; Abdominal Pain

Interventions

Amitriptyline; Escitalopram

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Yuri A. Saito Loftus
• Organization: Mayo Clinic

saito.yuri@mayo.edu

507-266-9094

Study Officials

• Earnest P Bouras, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• John K. DiBaise, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Colin P Howden, M.D.

  Northwestern University Chicago

  PRINCIPAL INVESTIGATOR

• Charlene M Prather, M.D.

  St. Louis University

  PRINCIPAL INVESTIGATOR

• Nicholas J Talley, M.D.,Ph.D.

  Mayo Clinic

  STUDY CHAIR

• Brian E. Lacy, M.D., Ph.D.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• G. R. Locke, III, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Bincy P Abraham, M.D., M.S.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Hashem El-Serag, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Paul Moayyedi, M.D.

  McMaster University Centre, Hamilton, Ontario

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 3, 2005
• First Posted: November 4, 2005
• Study Start: October 1, 2006
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 25, 2014
• Results First Posted: July 25, 2014

Record last verified: 2014-06

Locations

US (7); CA (1)