Clinical trial NCT06506136: Evaluation of Fluoxetine in Refractory Constipation With Comorbid Anxiety and Depression Treatment
Official title: Evaluation of the Efficacy of Fluoxetine in the Treatment of Refractory Constipation With Comorbid Anxiety and Depression: a Multicenter, Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Refractory Constipation
Keywords: refractory constipation
fluoxetine
Lead sponsor: Xijing Hospital of Digestive Diseases
Sponsor class: OTHER
First posted: 2024-07-17
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, placebo-controlled study to evaluate the efficacy and safety of fluoxetine in treating patients with refractory constipation and comorbid anxiety and depression.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to determine if fluoxetine is effective in treating refractory constipation and comorbid anxiety and depression . It will also assess the safety profile of fluoxetine when used for this condition. The main questions it aims to answer are:

Does fluoxetine improve bowel movement frequency and Complete Spontaneous Bowel Movements (CSBM) in participants with refractory constipation comorbid anxiety and depression? What adverse effects do participants experience while taking fluoxetine? Researchers will compare fluoxetine to a placebo (a look-alike substance that contains no active drug) to evaluate its efficacy and safety in treating chronic constipation.

Participants will:

Take fluoxetine or a placebo daily for 12 weeks Maintain a diary of their CSBM, Spontaneous Bowel Movements (SBM), bowel movements, stool consistency, and any side effects experienced


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

1. Meeting the Rome IV diagnostic criteria for functional constipation.
2. ≤2 CSBMs per week during the 2-week screening period.
3. Dissatisfaction with previous treatments of at least 3 months' duration, which included at least one class of promotility agents such as laxatives.
4. A score of ≥7 on either the Hamilton's Rating Scale for Anxiety (HAMA) or the Hamilton's Rating Scale for Depression (HAMD).
5. Age between 18 and 60 years.
6. Not participating in any other ongoing clinical trials.
7. Participants who voluntarily signed informed consent.

Exclusion criteria

1. Presence of organic diseases (e.g., tuberculosis, polyps, 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).
2. Requirement for long-term use of other medications that may affect bowel function or induce constipation, such as antiparkinsonian drugs (excluding routine laxatives, antidiarrheals, and bowel stimulants; during the trial, participants were permitted to use only designated rescue medications, and medication use was to be meticulously recorded).
3. Chronic pain lasting more than 6 months or a Visual Analogue Scale (VAS) pain score ≥4.
4. Diagnosis of psychiatric disorders with continuous use of psychotropic medications for more than 3 months prior to enrolment, or a history of psychotropic or corticosteroid use exceeding 3 months before enrolment.
5. Individuals assessed by psychiatrists to be at risk of self-harm or suicide, or those requiring psychosomatic intervention.
6. History of allergy to psychotropic drugs, known hypersensitivity to fluoxetine, or contraindications to fluoxetine (e.g., hepatic or renal impairment, prolonged QT interval on ECG).
7. Pregnant or lactation women.
8. Patients with other benign or malignant tumors, or autoimmune diseases.
9. Patients with cardiovascular diseases, coagulation disorders (e.g., regular use of warfarin or heparin), hepatic or renal diseases, organ failure, cognitive impairment, aphasia, or other chronic illnesses requiring long-term medication that could affect quality of life or interfere with study assessments and treatment outcomes.

Primary outcomes:
measure: Efficacy rate of fluoxetine treatment
timeFrame: Weeks-2-0, 1, 3, 5, 6, 7, 8，9，10，11，12
Secondary outcomes:
measure: Proportion of patients with ≥3 CSBM per week
timeFrame: Weeks-2-0, 1, 3, 5, 6, 7, 8，9，10，11，12
measure: Change in the SBM compared to baseline over the 12-week treatment period
timeFrame: Weeks-2-0, 1, 3, 5, 6, 7, 8，9，10，11，12
measure: Change in the average straining score for SBM over 12 weeks compared to baseline
timeFrame: Weeks-2-0, 1, 3, 5, 6, 7, 8，9，10，11，12
measure: Change in the abdominal bloating score compared to baseline over the 12-week treatment period
timeFrame: Weeks-2-0, 1, 3, 5, 6, 7, 8，9，10，11，12
measure: Change in the average stool consistency score for SBM over 12 weeks compared to baseline
timeFrame: Weeks -2-0, 1, 3, 5, 6, 7, 8, 9, 10, 11, 12
measure: Time to first CSBM after treatment initiation
timeFrame: Weeks-2-12
measure: Proportion of participants using rescue medications (polyethylene glycol or enema) and the weekly dosage of rescue medications used
timeFrame: Weeks -2-0, 1, 3, 5, 6, 7, 8, 9, 10, 11, 12
measure: The change in KESS score from baseline to the end of the treatment period
timeFrame: Weeks-2-0, 12
measure: Change in PAC-QOL self-assessment scores from baseline
timeFrame: Weeks -2-0, 12
measure: The change in HAMA score from baseline to the end of the treatment period
timeFrame: Weeks-2-0, 12
measure: The change in HAMD score from baseline to the end of the treatment period
timeFrame: Weeks-2-0, 12
measure: Medication adherence
timeFrame: Weeks 0-12
measure: Incidence of adverse events
timeFrame: Weeks-2-12
Other outcomes:
Locations:
city: Yinchuan
country: China
facility: People's Hospital of Ningxia Hui Autonomous Region
state: Ningxia
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
state: Shaanxi
Study officials:
affiliation: Xijing Hospital of Digestive Diseases
name: Qingchuan Zhao, Prof.
role: STUDY_CHAIR
References: