Transcranial Alternating Current Stimulation for Refractory Constipation With Somatic Symptom Disorder

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

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.

Inclusion Criteria:

1. Diagnosis of Functional Constipation (FC): Subjects must meet the diagnostic criteria for functional constipation as defined by the Rome IV criteria.

2. Low Frequency of Complete Spontaneous Bowel Movements (CSBM): During the 2-week screening period, subjects must have ≤2 complete spontaneous bowel movements per week.

3. 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).

4. 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:

     1. Excessive and persistent thoughts about the severity of symptoms;
     2. Persistently high levels of anxiety about health or symptoms;
     3. Excessive time and energy devoted to health concerns or symptoms.

   • Criterion C: Symptoms must persist for at least 6 months.

5. Age Range: Subjects must be between 18 and 80 years old.

6. No Concurrent Clinical Trials: Subjects must not participate in any other clinical trials during the study period.

7. Informed Consent: Subjects must voluntarily agree to participate and sign an informed consent form.

Exclusion Criteria:

1. 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);
2. 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);
3. History of chronic pain or substance abuse, such as opioids;
4. 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;
5. Individuals at risk of self-harm or suicide, as assessed by a psychiatrist, or those requiring psychosomatic intervention;
6. 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;
7. Pregnant or breastfeeding women;
8. Patients with benign or malignant tumors or autoimmune diseases;
9. 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.