Evaluation of Fluoxetine for Refractory Constipation With Somatic Symptom Disorder Features

NCT06506136 | Not Yet Recruiting Phase 1

• 1 other identifier: KY20242190
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this randomized, double-blind, placebo-controlled trial is to determine whether fluoxetine is effective and safe for adults with refractory constipation that exhibits Somatic Symptom Disorder (SSD) features-namely, persistent preoccupation with bowel function, heightened perception of defecatory discomfort, and clinically significant somatic symptom burden (PHQ-15 ≥ 10) in the absence of IBS-C abdominal pain criteria. The study will address three primary questions: Efficacy-Bowel Function:

• Does 12 weeks of fluoxetine increase Complete Spontaneous Bowel Movements (CSBM) and overall bowel-movement frequency compared with placebo? Efficacy-Somatic Symptom Burden:
• Does fluoxetine reduce SSD severity, as measured by the Patient Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Scale-8 (SSS-8)? Safety and Tolerability:
• What adverse events occur during fluoxetine treatment, and how do their incidence and intensity compare with placebo?

Conditions

Refractory Constipation; Somatic Symptom Disorder (DSM-5); Functional Constipation (FC)

Keywords

refractory constipation; fluoxetine; somatic symptom disorder; functional constipation

Outcome Measures

Primary Outcomes (1)

• Efficacy rate of fluoxetine treatment

  The primary efficacy endpoint is the proportion (%) of participants who achieve an increase of ≥ 1 complete spontaneous bowel movement (CSBM) per week relative to baseline in at least four of the twelve treatment weeks, a key indicator of therapeutic response in functional constipation (FC).

  Baseline (Week -2) through the end of Week 12 (treatment period)

Secondary Outcomes (12)

• Proportion of Participants Achieving ≥3 CSBM per Week

  baseline and 12-week

• Change in the SBM compared to baseline over the 12-week treatment period

  Baseline to Week-12

• Change from Baseline in Weekly CSBM Frequency

  Baseline to Week-12

• Change in the average straining score for SBM over 12 weeks compared to baseline

  Baseline to Week-12

• Change in the abdominal bloating score compared to baseline over the 12-week treatment period

  Baseline to Week-12

Study Arms (2)

Fluoxetine Treatment Group

EXPERIMENTAL

Drug: Fluoxetine

Placebo Control Group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Fluoxetine DRUG

Participants will receive fluoxetine tablets, 40 mg once daily, administered 30 minutes after breakfast for 12 weeks. Emergency Rescue Medications: For participants in both groups who cannot have a bowel movement for three consecutive days or have intolerable symptoms, the following rescue medications will be provided: polyethylene glycol：13.7 g enema Use of rescue medications must be recorded in the bowel movement diary and CRF, including date, time, and dosage. Rescue medications will be provided throughout the study but are not allowed within 48 hours before and after the first treatment. Distributed every two weeks, any bowel movements within 24 hours after rescue medication use will not count as CSBM.

Fluoxetine Treatment Group

Placebo DRUG

Participants in the Placebo Control Group will receive placebo tablets that are identical in appearance and taste to the fluoxetine tablets. They will take one placebo tablet orally twice a day for 12 weeks, following the same schedule as the treatment group to maintain blinding. Emergency Rescue Medications: For participants in both groups who cannot have a bowel movement for three consecutive days or have intolerable symptoms, the following rescue medications will be provided: polyethylene glycol：13.7 g enema Use of rescue medications must be recorded in the bowel movement diary and CRF, including date, time, and dosage. Rescue medications will be provided throughout the study but are not allowed within 48 hours before and after the first treatment. Distributed every two weeks, any bowel movements within 24 hours after rescue medication use will not count as CSBM.

Placebo Control Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• Diagnosis of Functional Constipation (FC): Participants must meet the diagnostic criteria for functional constipation according to Rome IV criteria.
• Low CSBM Frequency: During the 2-week screening period, participants must experience Complete Spontaneous Bowel Movements (CSBM) ≤ 2 times per week.
• Unsatisfactory Previous Treatments: Participants must have been dissatisfied with previous treatments for functional constipation, having undergone at least 3 months of treatment, including laxatives or other prokinetic agents.
• Diagnosis of Somatic Symptom Disorder (SSD): Participants must meet the diagnostic criteria for Somatic Symptom Disorder (SSD) according to DSM-5. All participants will undergo a semi-structured clinical interview based on DSM-5 criteria, conducted by professionals trained in SSD diagnosis.
• Criterion A: One or more physical symptoms that cause significant discomfort and/or disruption in daily life.
• Criterion B: At least one of the following: 1) Excessive and persistent thoughts about the severity of symptoms. 2) Persistent high anxiety about health or symptoms. 3) Excessive time and energy spent on health concerns or symptoms.
• Criterion C: The symptoms have persisted for at least 6 months.
• Age Range: Participants must be between the ages of 18 and 60 years.
• Not Participating in Other Ongoing Trials: Participants must not be involved in any other clinical trials during the study period.
• Informed Consent: Participants must voluntarily agree to participate in the study and sign an informed consent form.
• Organic Diseases: Participants with organic diseases (e.g., tuberculosis, Crohn's disease, tumors, congenital megacolon), endocrine disorders (e.g., hypothyroidism), metabolic diseases (e.g., diabetes, thyroid dysfunction), or neurological disorders (e.g., Parkinson's disease).
• Use of Medications Affecting Bowel Function: Participants who require long-term use of medications that may affect bowel function or induce constipation, such as Parkinson's medications, except for routine laxatives, antidiarrheal agents, and intestinal stimulants. Note: During the trial, participants are only allowed to use the specified emergency medications, and all medication use must be carefully recorded.
• Chronic Pain or Substance Abuse: Participants with a history of chronic pain lasting more than 6 months or with a pain score ≥4 (based on the visual analog scale), or a history of substance abuse.
• Mental Health Disorders: Participants diagnosed with psychiatric disorders before the study and continuously using psychiatric medications for more than 3 months, or those with a history of using psychiatric medications and/or corticosteroids for more than 3 months before the study.
• Self-harm or Suicide Risk: Participants with a risk of self-harm or suicide, as assessed by a psychologist, or those requiring psychophysical interventions.

Sponsors & Collaborators

• Zhifeng Zhao, PhD: lead

Study Sites (2)

People's Hospital of Ningxia Hui Autonomous Region

Yinchuan, Ningxia, 750021, China

Location

Xi'an International Medical Center Hospital

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Constipation

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Qingchuan Zhao, Prof.

  Xijing Hospital of Digestive Diseases

  STUDY CHAIR

Central Study Contacts

Qingchuan Zhao, Prof.

CONTACT

13809153899; zhaoqc@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Model Details: This study uses a randomized, double-blind, placebo-controlled "Parallel Assignment" design with two arms: Experimental Arm - Fluoxetine 20 mg qd Control Arm - Matching Placebo qd Participants are assigned in a 1 : 1 ratio by a central interactive web-response system, using permuted blocks stratified by study center and baseline CSBM frequency. Each participant receives only one intervention for the entire 12-week treatment period (plus taper/follow-up), with no crossover between arms.

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 17, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): May 30, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: For more information or to submit a request, please contact zhaozhifeng@outlook.com.

Locations

CN (2)