Individualized TCM Pattern-Based Thread-Embedding Acupuncture Plus Auricular Acupressure for Chronic Insomnia

This is a randomized, participant- and outcome-assessor-blinded, active-controlled, parallel-group clinical trial enrolling 70 adults aged 40 to 75 years with Chronic Insomnia Disorder diagnosed according to the International Classification of Sleep Disorders, Third Edition (ICSD-3).

Eligible participants must also meet prespecified diagnostic criteria for one of two Traditional Chinese Medicine patterns:

• Heart-Spleen Deficiency, or
• Liver Qi Stagnation with Spleen Deficiency. Participants will be randomly allocated in a 1:1 ratio to an individualized TCM pattern-based treatment group or a standardized treatment group.

Individualized treatment group Participants will receive thread-embedding acupuncture and auricular acupressure using acupoints selected according to their prespecified TCM pattern diagnosis.

Standardized treatment group Participants will receive the same treatment modalities using a fixed set of acupoints applied irrespective of TCM pattern.

Thread-embedding acupuncture will be performed twice, at baseline and Week 4. Auricular acupressure using Vaccaria seeds will be initiated at baseline and renewed every 2 weeks during the 6-week treatment period. Participants will be instructed to self-massage the auricular points for 1-2 minutes per point, 3-5 times daily, particularly approximately 30 minutes before bedtime.

The active treatment period will last 6 weeks, followed by a 4-week post-treatment follow-up, with the final assessment at Week 10. The Week 10 assessment is intended to evaluate the persistence of clinical effects after treatment discontinuation.

Sleep outcomes will be assessed using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). Gastrointestinal symptoms will be assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Adverse events will be monitored throughout the study.

Serum IL-6 and fecal calprotectin will be measured at baseline and Week 6. These biomarkers are considered exploratory mechanistic outcomes representing systemic and gut-related inflammatory activity. Because the study does not directly assess gut microbiota composition, microbial metabolites, intestinal permeability, or central nervous system biomarkers, IL-6 and fecal calprotectin will not be interpreted as direct measures or proof of a microbiota-gut-brain axis mechanism.

Biomarker sampling procedures Baseline biomarker samples will be collected before the first study intervention. If a participant has an acute febrile illness or clinically significant acute infection at a scheduled biomarker assessment, blood and stool sampling may be postponed within a prespecified allowable window according to the biomarker sampling standard operating procedure (SOP). For baseline assessments, the first study intervention will not be initiated until pretreatment biomarker samples have been collected. For the Week 6 assessment, biomarker sampling may be rescheduled within the prespecified allowable window without requiring withdrawal from the clinical study. The participant will remain in the study unless the acute illness otherwise meets a protocol-defined criterion for treatment discontinuation or study withdrawal.

Prespecified analytic components

The study includes two distinct prespecified analytic components:

• Randomized treatment-effect analysis The primary analysis will compare the clinical efficacy of individualized TCM pattern-based treatment with the standardized treatment protocol according to randomized treatment assignment. The primary clinical endpoint will be the between-group difference in change in PSQI score from baseline to Week 6.

Changes in ISI, GSRS, IL-6, fecal calprotectin, and adverse events will be evaluated as secondary or exploratory outcomes.

• Exploratory baseline phenotyping analysis

A separate exploratory analysis using pretreatment data only will examine whether Heart-Spleen Deficiency and Liver Qi Stagnation with Spleen Deficiency represent clinically and biologically distinguishable phenotypes. This analysis will examine:

• differences in insomnia severity between the two TCM patterns;
• differences in baseline serum IL-6;
• differences in baseline fecal calprotectin;
• associations of IL-6 with insomnia severity;
• associations of fecal calprotectin with insomnia severity; and
• whether these biomarker-insomnia associations differ according to TCM pattern. The baseline phenotyping analysis will not evaluate randomized treatment efficacy or post-treatment treatment effects.

All mechanistic and baseline phenotyping analyses will be considered exploratory and hypothesis-generating.

Inclusion criteria

Age 40 to 75 years. Diagnosis of Chronic Insomnia Disorder according to ICSD-3 criteria. Pittsburgh Sleep Quality Index (PSQI) score ≥5. Insomnia Severity Index (ISI) total score ≥10. Mini-Mental State Examination (MMSE) score >24. Diagnosis of one of the following prespecified Traditional Chinese Medicine patterns: Heart-Spleen Deficiency; or Liver Qi Stagnation with Spleen Deficiency.

TCM pattern diagnosis established according to prespecified standardized diagnostic criteria by a trained TCM practitioner.

Participants with hypertension or diabetes may be included if the condition is clinically stable, with no relevant change in medication regimen during the previous 3 months.

Able and willing to provide blood and stool samples according to study procedures.

Able to understand the study procedures and voluntarily provide written informed consent.

Exclusion criteria

Insomnia primarily attributable to another medical, neurological, psychiatric, or sleep disorder requiring alternative management.

Current acute or chronic gastrointestinal inflammatory disease, including inflammatory bowel disease, or acute diarrhea.

Known Crohn's disease or ulcerative colitis. Use of systemic corticosteroids, antibiotics, probiotics, or prebiotics within 4 weeks before baseline biomarker sampling.

Use of proton pump inhibitors within 2 weeks before baseline stool sampling. Regular use of non-steroidal anti-inflammatory drugs. Enema or colonoscopy within 1 month before stool sampling. Active autoimmune or systemic inflammatory disease, including rheumatoid arthritis.

Vaccination within 2 weeks before blood sampling. Acute infection or febrile illness at the time of biomarker assessment. Advanced renal, hepatic, or cardiovascular disease, including estimated glomerular filtration rate <45 mL/min/1.73 m², advanced hepatic failure, or New York Heart Association class III-IV heart failure.

Severe nocturia, defined as ≥3 episodes per night. Known obstructive sleep apnea or a high clinical likelihood of obstructive sleep apnea requiring further diagnostic evaluation.

Pregnancy or breastfeeding. Any clinical condition considered by the investigators to interfere substantially with sleep assessment, inflammatory biomarker interpretation, treatment safety, or protocol adherence.