Evaluation of Fluoxetine for Refractory Constipation With Somatic Symptom Disorder Features

Official title

Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Fluoxetine in Patients With Refractory Constipation Exhibiting Somatic Symptom Disorder Features

Overview

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?

Interventions

• Drug Fluoxetine
  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 pro
• Drug Placebo
  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 g

Primary outcome measures

• Efficacy rate of fluoxetine treatment [Time frame: Baseline (Week -2) through the end of Week 12 (treatment period)]

Secondary outcome measures (12)

• Proportion of Participants Achieving ≥3 CSBM per Week [Time frame: baseline and 12-week]
• Change in the SBM compared to baseline over the 12-week treatment period [Time frame: Baseline to Week-12]
• Change from Baseline in Weekly CSBM Frequency [Time frame: Baseline to Week-12]
• Change in the average straining score for SBM over 12 weeks compared to baseline [Time frame: Baseline to Week-12]
• Change in the abdominal bloating score compared to baseline over the 12-week treatment period [Time frame: Baseline to Week-12]
• Change in the average stool consistency score for SBM over 12 weeks compared to baseline [Time frame: Baseline to Week-12]
• The change in KESS score from baseline to the end of the treatment period [Time frame: Baseline to Week-12]
• Change in PAC-QOL self-assessment scores from baseline [Time frame: Baseline to Week-12]
• The change in GAD-7 score from baseline to the end of the treatment period [Time frame: Baseline to Week-12]
• The change in PHQ-9 score from baseline to the end of the treatment period [Time frame: Baseline to Week-12]
• The change in PHQ-15 score from baseline to the end of the treatment period [Time frame: Baseline to Week-12]
• Incidence of adverse events [Time frame: Weeks-2-12]

Eligibility criteria

Participants in this study were recruited from a real-world outpatient constipation patient registry platform, which provides a comprehensive case database to support evidence-based research. Based on the characteristics of the primary target population identified in previous studies of fluoxetine, participants with refractory constipation were selected from the registry according to the following criteria:

All participants were required to meet the Rome IV diagnostic criteria for functional constipation.Specifically: 1) At least two of the following symptoms must be present during more than 25% of defecations: straining; lumpy or hard stools; sensation of incomplete evacuation; sensation of anorectal obstruction/blockage; manual maneuvers to facilitate defecation; fewer than three spontaneous bowel movements per week; 2) Loose stools are rarely present without the use of laxatives; 3) The criteria for IBS were not met.

Symptoms must have been present for at least six months prior to diagnosis, with the diagnostic criteria fulfilled during the last three months. Participants who met the diagnostic criteria were further assessed against the inclusion and exclusion criteria outlined below. Patients who did not meet any inclusion criteria or met any exclusion criteria were not recruited.

Inclusion criteria

• 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.

4.1. Criterion A: One or more physical symptoms that cause significant discomfort and/or disruption in daily life.

4.2. 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.

4.3. 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.

Exclusion criteria

• 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.
• Allergic Reactions or Contraindications to Psychiatric Medications: Participants with a history of allergy to psychiatric medications, including fluoxetine, or those with liver or kidney dysfunction, or any contraindications for fluoxetine, such as prolonged QT interval on ECG.
• Pregnant or Breastfeeding Women: Pregnant or breastfeeding women.
• Other Malignant or Benign Tumors: Participants with other malignant or benign tumors or autoimmune diseases.
• Chronic Diseases Impacting Life Quality: Participants with cardiovascular diseases, clotting disorders (e.g., those on long-term warfarin or heparin therapy), liver or kidney diseases, organ failure, cognitive disorders, aphasia, or any other chronic diseases requiring long-term medication, which may significantly affect their quality of life and the evaluation of treatment outcomes.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• People's Hospital of Ningxia Hui Autonomous Region — Yinchuan
• Xi'an International Medical Center Hospital — Xi'an

Identifiers

NCT: NCT06506136 · KY20242190

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗