Predicting Treatment Outcomes in Refractory Constipation Through Brain Connectivity Evaluation

Recruiting

• Conditions: Brain Connectivity; Constipation - Functional; Somatic Symptom; Mental Symptom; Fluoxetine; Treatment Efficacy; Refractory Constipation; fMRI
• Interventions: Diagnostic Test: BOLD-fMRI; Drug: Regular treatment of functional constipation; Drug: fluoxetine

• Registration Number: NCT06221722
• Lead Sponsor: Xijing Hospital of Digestive Diseases

Brief Summary

The goal of this observational study is to identify the characteristics of brain functional connectivity in refractory constipation and fluoxetine-sensitive patients. The main questions it aims to answer are:

* Investigating the alterations in brain functional connectivity in patients with refractory constipation and fluoxetine-sensitive patients

* Assessing the predictive value of brain functional connectivity regarding the efficacy of fluoxetine and standard protocol treatments for constipation.

Participants will receive:

* Standard physiological and psychological assessments of constipation

* BOLD-fMRI tests

* Standard protocol and fluoxetine treatment

If there is a comparison group: Researchers will compare:

Refractory group/Fluoxetine sensitive group to see the specific brain alterations.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-01
• Study First Submitted: 2023-12-26
• Status Verified: 2024-01
• Study First Submitted QC: 2024-01-14
• Study First Posted: 2024-01-24
• Last Update Submitted: 2024-01-28
• Last Update Posted: 2024-01-30
• Primary Completion: 2025-09-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• 18≤ age ≤ 45 years old
• Right-handed
• Patients diagnosed as functional constipation according to the Rome IV criteria
• Informed consent of patients

Exclusion Criteria

• Complicated with gastrointestinal organic disease or significant functional abnormalities (tuberculosis, polyps, Crohn's disease, tumors, congenital megacolon, pelvic floor muscle relaxation, abnormal colonic transit test, etc.)
• Long-term intense exercise (continuous exercise for more than 8 hours per week, such as marathon runners or triathletes)
• No history of chronic pain, no recent major trauma
• Drug abuse or tobacco dependence (half a pack or more per day)
• Combined hypothyroidism and Parkinson's disease
• Patients with confirmed mental illness or neurological disorders who take psychotropic drugs, analgesics or hormones
• History of abdominal surgery (appendectomy, hysterectomy, or cholecystectomy)
• Contraindications to functional magnetic resonance imaging (claustrophobia, metal implants)
• Pregnant or lactating women with constipation after delivery
• Patients with other benign and malignant tumors and autoimmune diseases
• Infectious diseases such as hepatitis B, hepatitis C, AIDS, etc.
• Heart disease, organ failure and other chronic diseases that require long-term medication or affect the quality of life

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Refractory constipation: fluoxetine insensitive	Regular treatment of functional constipation	Functional constipation patients maintained at least 3 months of continuous regular therapy with ineffective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet. After 3 months of regular treatment, patients received fluoxetine therapy for 4-week with ineffective treatment of constipation symptoms.
Refractory constipation: fluoxetine sensitive	BOLD-fMRI	Functional constipation patients maintained at least 3 months of continuous regular therapy with ineffective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet. After 3 months of regular treatment, patients received fluoxetine therapy for 4-week with effective treatment of constipation symptoms.
Non-refractory constipation	Regular treatment of functional constipation	Functional constipation patients maintained at least 3 months of continuous regular therapy with effective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet.
Health Control	BOLD-fMRI	Volunteers without symptoms of constipation
Refractory constipation: fluoxetine insensitive	BOLD-fMRI	Functional constipation patients maintained at least 3 months of continuous regular therapy with ineffective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet. After 3 months of regular treatment, patients received fluoxetine therapy for 4-week with ineffective treatment of constipation symptoms.
Refractory constipation: fluoxetine sensitive	Regular treatment of functional constipation	Functional constipation patients maintained at least 3 months of continuous regular therapy with ineffective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet. After 3 months of regular treatment, patients received fluoxetine therapy for 4-week with effective treatment of constipation symptoms.
Non-refractory constipation	BOLD-fMRI	Functional constipation patients maintained at least 3 months of continuous regular therapy with effective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet.
Refractory constipation: fluoxetine sensitive	fluoxetine	Functional constipation patients maintained at least 3 months of continuous regular therapy with ineffective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet. After 3 months of regular treatment, patients received fluoxetine therapy for 4-week with effective treatment of constipation symptoms.
Refractory constipation: fluoxetine insensitive	fluoxetine	Functional constipation patients maintained at least 3 months of continuous regular therapy with ineffective treatment. The treatment included the utilization of osmotic laxatives, stimulant laxatives, prosecretory agents, and a high-fibre diet. After 3 months of regular treatment, patients received fluoxetine therapy for 4-week with ineffective treatment of constipation symptoms.

Primary Outcome Measures

Name	Time	Method
Brain functional connectivity changes in BOLD-fMRI examination in refractory constipation before and after fluoxetine treatment	1-week pre and 4-week post of fluoxetine treatment	BOLD-fMRI tests before and after fluoxetine treatment

Secondary Outcome Measures

Name	Time	Method
Changes in PAC-QOL self-assessment scores from baseline	1-week pre and 4-week post-fluoxetine treatment.	The Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire is a self-reported instrument designed to measure the quality of life in individuals with constipation. This tool comprises 28 items across four fundamental domains, including physical discomfort, worries and concerns, psychosocial discomfort, and satisfaction. In our study, the Chinese version (version 16) was utilized.
Changes in GAD-7 self-assessment scores from baseline.	1-week pre and 4-week post-fluoxetine treatment.	The Generalized Anxiety Disorder-7 (GAD-7) is a brief measure assessing the frequency of anxiety symptoms over the past two weeks. With 7 items, the scale concentrates on the core symptoms of generalized anxiety disorder, serving as an instrument to ascertain the level of anxiety and to monitor the improvement of anxiety symptoms.
Changes in PHQ-15 self-assessment scores relative to baseline.	1-week pre and 4-week post-fluoxetine treatment.	The Patient Health Questionnaire-15 (PHQ-15) is a self-reporting inventory that evaluates the severity of somatic symptoms in patients. Comprising 15 items, the questionnaire primarily focuses on experienced bodily symptoms and aids healthcare providers in identifying potential somatization disorders or severe somatic illnesses.
Changes in PHQ-9 self-assessment scores since baseline.	1-week pre and 4-week post-fluoxetine treatment.	The Patient Health Questionnaire-9 (PHQ-9) is a tool used for screening, diagnosing, monitoring, and quantifying the severity of depression. The questionnaire consists of 9 items drawing from typical symptoms of depression, facilitating the evaluation of the presence and severity of depression by medical professionals.
Changes in KESS self-assessment scores from baseline.	1-week pre and 4-week post-fluoxetine treatment.	The KESS questionnaire, Kovacs' Evaluation of Sphincter Symptoms, is utilized to assess defecatory dysfunction. It includes a series of items that inquire about constipation symptoms and defecatory habits, aiming to evaluate the severity and impact of a patient's defecatory disorders.

Trial Locations

Locations (3)

People's Hospital of Ningxia Hui Autonomous Region; 🇨🇳 Yinchuan, Ningxia, China

Xi'an International Medical Center Hospital; 🇨🇳 Xi'an, Shaanxi, China

Xijing Hospital, Fourth Military Medical University; 🇨🇳 Xi'an, Shaanxi, China