Functional Dyspepsia Treatment Trial

Study Overview
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Brief Summary
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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
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The aims of this study were to: 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. 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.

Official Title
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Antidepressant Therapy for Functional Dyspepsia

Conditions
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Dyspepsia and Other Specified Disorders of Function of Stomach

Intervention / Treatment
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* Drug: Amitriptyline
* Drug: Escitalopram
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amitriptyline<br>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<br>* 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.<br>* Other names: Elavil;|
| Active Comparator: Escitalopram<br>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<br>* 10 mg tablets by mouth at bedtime for 12 weeks. The drug will be provided in blister packs.<br>* Other names: Lexapro;|
| Placebo Comparator: Placebo<br>Placebo escitalopram tablets and placebo amitriptyline capsules will be taken by mouth half an hour before bedtime for 12 weeks. | Drug: Placebo<br>* Placebo escitalopram and placebo amitriptyline will be manufactured to ensure all tablets and capsules will be indistinguishable, and provided in blister packs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric Emptying Half-Time (T1/2) | The time for half of the ingested solids or liquids to leave the stomach. | 12 weeks | 
| Maximum Tolerated Volume by Nutrient Drink Test | The nutrient drink test for meal-induced satiety had subjects drink 120 ml of ENSURE every four minutes. Satiety scores were measured on a scale graded 0-5 (1, no symptoms; 5, maximum satiety). When a score of 5 was reached, the maximum tolerated volume intake was measured. Abnormal satiety was defined as inability to consume > 800 ml of Ensure. | 12 weeks | 
| Dyspepsia-Specific Quality of Life | The Nepean Dyspepsia Index (NDI) assessed quality of life. NDI scores are summarized into overall quality of life and 5 subscales: Interference, Knowledge/Control, Eating/Drinking, Sleep Disturbance, Work/Study. The scale consists of 25 items, yielding 5 sub-scales. Range 0-100, higher numbers indicate a greater quality of life. | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bloating, Early Fullness, Nausea, Upper Abdominal Discomfort, dyspepsia, stomach pain, stomach discomfort