Evaluation of Fluoxetine for Refractory Constipation With Somatic Symptom Disorder Features

Phase 2Not Yet RecruitingNCT06506136

Zhifeng Zhao, PhD194 enrolled

Overview

This single-center, randomized, double-blind, placebo-controlled trial evaluates the efficacy and safety of fluoxetine (40 mg/day) versus placebo in 194 adults with refractory chronic constipation exhibiting Somatic Symptom Disorder (SSD) features diagnosed by SCID-5. After a 2-week screening period, participants are randomized 1:1 to fluoxetine or matching placebo for 12 weeks. The primary endpoint is the proportion of CSBM responders, defined as an increase of ≥1 CSBM per week from baseline in ≥50% of treatment weeks (Weeks 5-12). Key secondary endpoints include weekly SBM/CSBM frequency, Bristol Stool Form Scale, straining score, bloating severity, Patient Global Impression of Change (PGIC, 7-point), and changes in validated PRO scales (SSD-12, PHQ-15, PHQ-9, GAD-7, PAC-QOL, KESS). Mechanistic assessments include resting-state fMRI and high-resolution anorectal manometry (HRAM). Safety is monitored through adverse events, thyroid/liver/renal function tests, and ECG.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

194

Conditions

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

Interventions

FluoxetineDRUG

Participants receive fluoxetine orally after breakfast, starting at 20 mg/day (1 capsule) for the first 7 days. From Day 8, the dose increases to the target of 40 mg/day (2 capsules), maintained through Week 12. If a participant cannot tolerate the 40 mg dose, the dose may be reduced back to 20 mg/day; if 20 mg remains intolerable, the study drug is discontinued and the participant enters safety follow-up. Rescue medications: For participants in both groups who have no bowel movement for 3 consecutive days or experience intolerable symptoms, a two-tier rescue protocol is available: (1) first line: polyethylene glycol 13.7 g orally; (2) second line: glycerin enema if no response to PEG after 24-48 hours. Rescue medication use must be recorded in the bowel movement diary and eCRF (date, time, dose). Rescue medications are distributed at each 4-week visit. Any bowel movement occurring within 24 hours after rescue medication use is classified as non-spontaneous (non-SBM) and excluded from

PlaceboDRUG

Participants in the Placebo Control Group receive placebo tablets that are identical in appearance, taste, and packaging to the fluoxetine tablets. They take one placebo tablet orally once daily after breakfast for 12 weeks, following the same schedule as the treatment group to maintain blinding. Rescue medications: For participants in both groups who have no bowel movement for 3 consecutive days or experience intolerable symptoms, a two-tier rescue protocol is available: (1) first line: polyethylene glycol 13.7 g orally; (2) second line: glycerin enema if no response to PEG after 24-48 hours. Rescue medication use must be recorded in the bowel movement diary and eCRF (date, time, dose). Rescue medications are distributed at each 4-week visit. Any bowel movement occurring within 24 hours after rescue medication use is classified as non-spontaneous (non-SBM) and excluded from the CSBM/SBM endpoint calculation.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Diagnosis of Functional Constipation (FC): Participants must meet the Rome IV diagnostic criteria for functional constipation. 2. Low CSBM Frequency: During the 2-week screening period, participants must have Complete Spontaneous Bowel Movements (CSBM) ≤ 2 times per week. 3. Refractory to Standard Laxatives: Participants must have documented failure of at least 3 classes of conventional laxatives (e.g., osmotic, stimulant, or prosecretory agents), each administered at standard doses for ≥4 weeks. 4. Diagnosis of Somatic Symptom Disorder (SSD): Participants must meet the DSM-5 diagnostic criteria for Somatic Symptom Disorder, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5), conducted by trained professionals. 5. Age Range: Participants must be between 18 and 70 years of age. 6. No Concurrent Trial Participation: Participants must not be enrolled in any other interventional clinical trial during the study period. 7. Informed Consent: Participants must voluntarily provide written informed consent. Exclusion Criteria: 1. Organic or Secondary Causes: Participants with organic gastrointestinal diseases (e.g., colorectal cancer, Crohn's disease, congenital megacolon), endocrine disorders (e.g., hypothyroidism), metabolic diseases (e.g., diabetes), neurological disorders (e.g., Parkinson's disease), or prior major abdominal surgery (e.g., colectomy, cholecystectomy). 2. Medications Affecting Bowel Function: Participants requiring long-term use of medications known to affect gastrointestinal motility or induce constipation (e.g., antiparkinsonian drugs, opioids), except for routine laxatives. 3. Chronic Pain Requiring Opioids: Participants with chronic pain syndromes unrelated to functional gastrointestinal disorders (e.g., fibromyalgia, severe chronic back pain) who require long-term opioid therapy. 4. Recent Psychotropic Medication Use: Participants who have used any antidepressant, anxiolytic, or antipsychotic medication within 4 weeks prior to screening. 5. Severe Psychiatric Conditions: Participants at risk of self-harm or suicide, or with severe major depressive episode, severe anxiety disorder, bipolar disorder, or schizophrenia spectrum disorders, as assessed by a psychiatrist. 6. Contraindications to Fluoxetine: Participants with a history of hypersensitivity to fluoxetine or other SSRIs, hepatic or renal impairment, or ECG evidence of QTc prolongation. 7. Pregnancy, Lactation, or Planned Pregnancy: Women who are pregnant, breastfeeding, or planning to become pregnant during the study period. 8. Malignancy or Autoimmune Disease: Participants with active malignant or benign tumors, or autoimmune diseases. 9. Severe Comorbidities: Participants with cardiovascular diseases, coagulation disorders (requiring long-term anticoagulation), hepatic or renal failure, organ failure, cognitive impairment, or aphasia, where the chronic condition requires long-term medication affecting quality of life and treatment evaluation. 10. Recent Clinical Trial Participation: Participants who have participated in another interventional clinical trial within 3 months prior to screening.

Outcomes

Primary Outcomes

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 last eight weeks (Weeks 5-12), a key indicator of therapeutic response in functional constipation (FC).

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

Secondary Outcomes

Proportion of Participants Achieving ≥3 CSBM per Week

Percentage of participants who achieve at least 3 complete spontaneous bowel movements (CSBM) per week during the 12-week treatment period.

Time frame: baseline and 12-week

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

Refers to a bowel movement occurring within the past 24 hours without the use of rescue medications or any other adjunctive methods (e.g., laxatives, enemas, suppositories, or digital maneuvers), including CSBM