Transcranial Alternating Current Stimulation for Refractory Constipation With Somatic Symptom Disorder

Official title

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Transcranial Alternating Current Stimulation (tACS) for the Treatment of Refractory Constipation Comorbid With Somatic Symptom Disorder

Overview

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.

Interventions

• Device Transcranial Alternating Current Stimulation
  Electrode placement: Referenced to the forehead (Fpz) and bilateral mastoid regions, covering the prefrontal cortex and related brain-gut axis pathways. Stimulation parameters: Alternating current, 15 mA intensity, 77.5 Hz frequency. Dosing schedule: Once daily, 30-40 minutes per session, for 4 consecutive weeks (20 sessions total; Monday-Friday with weekend breaks).
• Device Placebo
  Electrode placement: Same as active-referenced to the forehead (Fpz) and bilateral mastoid regions, to mimic coverage of the prefrontal cortex and related brain-gut axis pathways. Stimulation parameters: Sham stimulation; the device is programmed to deliver a brief ramp-up and ramp-down at session start (e.g., ≤30 seconds total) to reproduce initial skin sensations, followed by no sustained current (0 mA effective intensity; no therapeutic stimulation). Dosing schedule: Once daily, 30-40 minut

Primary outcome measures

• The proportion (%) of patients who achieved an increase of ≥1 CSBM per week compared to baseline for at least 2 out of the 4 treatment weeks. [Time frame: 1-4 treatment week]

Secondary outcome measures (11)

• Proportion of participants achieving an increase of ≥1 CSBM from baseline in at least 2 weeks during follow-up [Time frame: Weeks 1-4 follow-up; assessed over the 4-week period]
• Change from baseline in weekly frequency of spontaneous bowel movements (SBM) [Time frame: Baseline and each week during Weeks 1-4]
• Change from baseline in weekly frequency of complete spontaneous bowel movements (CSBM) [Time frame: Baseline and each week during Weeks 1-4]
• Change from baseline in stool consistency (Bristol Stool Form Scale) for weekly SBMs [Time frame: Baseline and Weeks 3-4]
• Change from baseline in straining score for weekly SBMs (4-point scale: 0=no difficulty, 1=mild, 2=moderate, 3=severe) [Time frame: Baseline and Weeks 3-4]
• Change from baseline in abdominal bloating severity (5-point scale: 1=none, 2=mild, 3=moderate, 4=severe, 5=very severe) [Time frame: Baseline and Weeks 3-4]
• Change from baseline in Patient Health Questionnaire-9 (PHQ-9) score [Time frame: Baseline and Week 4]
• Change from baseline in Generalized Anxiety Disorder-7 (GAD-7) score [Time frame: Baseline and Week 4]
• Change from baseline in Patient Health Questionnaire-15 (PHQ-15) somatic symptom score [Time frame: Baseline and Week 4]
• Change from baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) [Time frame: Baseline and Week 4]
• Proportion of participants using polyethylene glycol (PEG) as rescue medication [Time frame: During the 4-week treatment period]

Eligibility criteria

Inclusion criteria

• Diagnosis of Functional Constipation (FC): Subjects must meet the diagnostic criteria for functional constipation as defined by the Rome IV criteria.
• Low Frequency of Complete Spontaneous Bowel Movements (CSBM): During the 2-week screening period, subjects must have ≤2 complete spontaneous bowel movements per week.
• Poor Response to Previous Treatment: Subjects must have been dissatisfied with prior treatments for functional constipation and have undergone at least 3 months of therapy (including laxatives or other prokinetic agents).
• Diagnosis of Somatic Symptom Disorder (SSD): Subjects must meet the DSM-5 diagnostic criteria for somatic symptom disorder (SSD). All subjects will undergo a semi-structured clinical interview based on DSM-5 criteria, conducted by professionals trained in SSD diagnosis.

• Criterion A: Presence of one or more distressing somatic symptoms that significantly affect daily life.
• Criterion B: At least one of the following must be met:

• Excessive and persistent thoughts about the severity of symptoms;
• Persistently high levels of anxiety about health or symptoms;
• Excessive time and energy devoted to health concerns or symptoms.
• Criterion C: Symptoms must persist for at least 6 months.
• Age Range: Subjects must be between 18 and 80 years old.
• No Concurrent Clinical Trials: Subjects must not participate in any other clinical trials during the study period.
• Informed Consent: Subjects must voluntarily agree to participate and sign an informed consent form.

Exclusion criteria

• Presence of organic diseases (such as tuberculosis, polyps, Crohn's disease, tumors, congenital megacolon, etc.), endocrine disorders (e.g., hypothyroidism), metabolic diseases (diabetes, thyroid dysfunction), or neurological disorders (e.g., Parkinson's disease);
• Long-term use of medications that may affect intestinal function or induce constipation, such as Parkinson's drugs (excluding conventional laxatives, antidiarrheals, or intestinal stimulants; during the trial, participants are only allowed to take prescribed emergency medications, with detailed records of usage required);
• History of chronic pain or substance abuse, such as opioids;
• Diagnosed mental disorders with psychotropic medication use for over 3 months prior to the visit, or history of psychotropic or hormonal medication use for over 3 months;
• Individuals at risk of self-harm or suicide, as assessed by a psychiatrist, or those requiring psychosomatic intervention;
• History of allergy to psychiatric medications (e.g., fluoxetine), or contraindications to fluoxetine such as liver/kidney impairment or prolonged Q-T interval on ECG;
• Pregnant or breastfeeding women;
• Patients with benign or malignant tumors or autoimmune diseases;
• Chronic conditions requiring long-term medication that may affect quality of life or interfere with examinations/treatment, including cardiovascular diseases, coagulation disorders or regular anticoagulant use (warfarin/heparin), liver/kidney diseases, organ failure, cognitive impairment, aphasia, etc.

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

• Xi'an International Medical Center Hospital — Xi'an
• Xijing Hospital — Xi'an

Identifiers

NCT: NCT07323407 · XJLL-KY-20252521

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗