Evaluation of Fluoxetine for Refractory Constipation With Somatic Symptom Disorder Features
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-70
SponsorZhifeng Zhao, PhD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of Functional Constipation (FC): Participants must meet the Rome IV diagnostic criteria for functional constipation.
Low CSBM Frequency: During the 2-week screening period, participants must have Complete Spontaneous Bowel Movements (CSBM) ≤ 2 times per week.
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.
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.
Disqualifiers
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).
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.
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.
Recent Psychotropic Medication Use: Participants who have used any antidepressant, anxiolytic, or antipsychotic medication within 4 weeks prior to screening.
Trial design
Design model
Parallel
Treatments tested in this trial
Fluoxetine
DrugParticipants 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
Placebo
DrugParticipants 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.
Treatment groups
194 Participants
are divided into 2 treatment groupsGroup A: Fluoxetine Treatment GroupExperimental treatment 1 intervention
Group B: Placebo Control GroupPlacebo comparator 1 intervention
Trial outcomes
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 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
1
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-week2
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
Time frame
Baseline to Week-123
Change from Baseline in Weekly CSBM Frequency
The mean change in weekly complete spontaneous bowel movements (CSBM) compared to baseline.
Time frame
Baseline to Week-124
Change in the average straining score for SBM over 12 weeks compared to baseline
0 = no difficulty; 1. = mild difficulty, straining required; 2. = moderate difficulty, straining required; 3. = severe difficulty, intense straining required.
Time frame
Baseline to Week-12Locations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Zhifeng Zhao, PhD
Lead sponsor
Xijing Hospital of Digestive Diseases
Sponsor institution
Source ClinicalTrials.gov
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