Refractory Constipation

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.

The goal of this clinical trial is to learn whether transcutaneous auricular vagus nerve stimulation (taVNS) works to treat refractory constipation in adults. It will also learn about the safety and tolerability of taVNS. The main questions it aims to answer are: Does taVNS improve constipation symptoms, as measured by the change in complete spontaneous bowel movements per week (ΔCSBMs/week) from baseline to post-treatment? What medical problems or side effects do participants have when receiving taVNS? Does taVNS reduce the need for rescue laxatives? Researchers will compare active taVNS to sham taVNS to see if taVNS works to treat refractory constipation. Participants will: Be randomly assigned (double-blind) to receive active taVNS or sham taVNS for 20 days Receive stimulation twice daily, 30 minutes per session, with a 12-hour interval between sessions Receive stimulation at 30 Hz with 200 μs pulse width, delivered to the left cymba conchae Keep a daily diary of bowel habits and symptoms, including CSBMs, and rescue laxative use (bowel movements occurring within 24 hours after rescue laxative use will not be counted as CSBMs)

The purpose of this randomized, double-blind, placebo-controlled trial is to evaluate the efficacy and safety of transcranial alternating current stimulation (tACS) in adults with refractory functional constipation comorbid with somatic symptom disorder. This population is characterized by persistent bowel dysfunction despite conventional treatments, frequent reliance on laxatives, and evidence of impaired brain-gut regulation contributing to chronic symptoms. The study focuses on three primary domains: Efficacy - Bowel Function: • Assessment of whether a 4-week course of tACS improves bowel activity, measured by changes in Complete Spontaneous Bowel Movements (CSBM) and overall bowel-movement frequency over the treatment and follow-up period. Efficacy - Symptom and Quality of Life Burden: • Evaluation of the effect of tACS on constipation-related severity and patient-reported outcomes, including the Patient Assessment of Constipation-Symptoms (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL). Safety and Tolerability: • Documentation of adverse events associated with tACS, with particular attention to incidence, intensity, and overall patient tolerability compared with sham stimulation.

This research protocol outlines a two-year descriptive cross-sectional study to investigate the role of high-resolution anorectal manometry (HRAM) in children aged 4-18 years with chronic refractory constipation.The study plans to enroll 54 patients at Ain Shams University Specialized Hospital . The study aims to identify different patterns of anorectal dysfunction (like dyssynergic defecation or rectal hyposensitivity) using standardized international protocols. A key goal is to determine if these manometry findings can directly guide specific management strategies, such as biofeedback therapy for dyssynergia or botulinum toxin injections for anal hypertension. improving outcomes for children who do not respond to standard constipation therapies.

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.