Duloxetine in Inflammatory Bowel Diseases (Duloxetine in)

A Phase II Open-label Study of Duloxetine to Reduce Inflammatory Bowel Disease-Related Disability and Psychological Distress

This open-label, prospective, single-arm pilot study investigates the use of duloxetine, a central neuromodulator, for improving psychological distress and functional impairment in adults with inflammatory bowel disease (IBD). The study focuses on patient-reported outcomes related to anxiety, depression, and IBD-related disability, aiming to assess feasibility, tolerability, and preliminary efficacy in modulating gut-brain axis symptoms and disease-related functional impairments in life

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Drug: Duloxetine

Detailed Description

Subjects will be screened and enrolled once PI confirms eligibility. After patient signs consent:

Duloxetine 30 mg orally daily will be administered for 1 week (age <65 years) or 2 weeks (age ≥65 years), then increased to duloxetine 60 mg orally daily, if tolerated.

Patients may continue duloxetine 30 mg if they do not tolerate duloxetine 60 mg.

Patients will receive 30-60 mg of duloxetine for 6 weeks, followed by a tapering period of 2 weeks at the end of treatment, mailed to their home address. Patients who wish to continue taking duloxetine after the trial may contact their primary care provider to obtain a prescription for duloxetine.

Patient reported outcomes will be completed at set intervals.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chung Tse, MD; Phone Number: 2153498222; Email: Chung.Tse@Pennmedicine.upenn.edu
• Study Contact Backup: Name: Maureen DeMarshall, BSN, RN; Phone Number: 2153498546; Email: demarshm@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults over 24 years old; (younger patients are excluded because antidepressants have been shown to increase the risk of suicidal thinking and behavior in patients ≤ 24 years old.)

• At least one of the following:

  1. elevated psychological distress (Distress Thermometer score > 4),10-12
  2. moderate-to-severe IBD-related disability (IBD-DI score ≥ 356, 7), or
  3. elevated GI-specific anxiety (Visceral Sensitivity Index > 10) -

Exclusion Criteria:

• Concomitant use of antidepressants (including serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, buspirone, and thioridazine).
• Initiation of psychotherapy within 8 weeks.
• Inability or unwillingness to monitor ambulatory blood pressure and receive a blood pressure monitor via postal mail.
• Cirrhosis with clinically evident hepatic insufficiency (Child-Pugh Class B or C) by medical record review.1
• Severe renal impairment (on dialysis; chronic kidney disease stage 4-5; acute kidney injury with glomerular filtration rate <30 mL/minute) by medical record review of labs performed within 18 months.
• Concurrent participation in another clinical trial of an investigational medicinal product.
• Pregnant or lactating either by self-report or medical record review
• Glaucoma
• Gastroparesis
• Use of medications that could lead to serious interactions with the study medication: potent CYP1A2 inhibitors, antidepressants (including serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, buspirone, thioridazine), linezolid, intravenous methylene blue, triptans, lithium, fentanyl, tramadol, meperidine, methadone, tryptophan, amphetamines, and St. John's Wort.
• Bipolar, psychotic, alcohol use disorder, non-alcohol substance-induced disorders, or imminent danger to self or others

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duloxetine; Duloxetine 30-60 mg daily per oral	Drug: Duloxetine; antidepressant; central neuromodulator; Other Names: cymbalta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IBD-related disability	IBD Disability Index scores, range 0-100, higher score indicates more disability	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in psychological distress	Depression Anxiety and Stress Scale (DASS-21), range 0-21, higher scores indicate higher distress Distress Thermometer, range 0-10, higher scores indicate higher distress	6 weeks
Tolerability and safety	Determine the tolerability and safety of duloxetine (30-60 mg daily)	6 weeks
Changes in gastrointestinal-specific anxiety	Visceral Sensitivity Index (VSI), range 0-75, higher scores indicate more gastrointestinal-specific anxiety	6 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Publications and helpful links

General Publications

• Birkinshaw H, Friedrich CM, Cole P, Eccleston C, Serfaty M, Stewart G, White S, Moore RA, Phillippo D, Pincus T. Antidepressants for pain management in adults with chronic pain: a network meta-analysis. Cochrane Database Syst Rev. 2023 May 10;5(5):CD014682. doi: 10.1002/14651858.CD014682.pub2.
• Khasawneh M, Mokhtare M, Moayyedi P, Black CJ, Ford AC. Efficacy of gut-brain neuromodulators in irritable bowel syndrome: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2025 Jun;10(6):537-549. doi: 10.1016/S2468-1253(25)00051-2. Epub 2025 Apr 18.
• Daghaghzadeh H, Naji F, Afshar H, Sharbafchi MR, Feizi A, Maroufi M, Tabatabaeeyan M, Adibi P, Tavakoli H. Efficacy of duloxetine add on in treatment of inflammatory bowel disease patients: A double-blind controlled study. J Res Med Sci. 2015 Jun;20(6):595-601. doi: 10.4103/1735-1995.165969.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: January 21, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiophenes; Duloxetine Hydrochloride
• Other Study ID Numbers: 859508

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes