Tiaoshen Anti-cancer Protocol and CBT for Insomnia and Survival in Ovarian Cancer

Tiaoshen Anti-cancer Protocol and CBT for Insomnia and Survival in Ovarian Cancer: A Multicenter Randomized Trial

Study Title: A Multicenter, Randomized Controlled Trial of Tiaoshen Anti-cancer Protocol Combined with Cognitive Behavioral Therapy for Insomnia in Improving Sleep and Survival in Ovarian Cancer Patients Purpose: This study aims to evaluate whether a combined therapy of traditional Chinese medicine (TCM) and modern psychotherapy can improve sleep and potentially extend survival for patients with ovarian cancer. Many patients experience severe, cancer-related insomnia, which lowers quality of life and may affect treatment outcomes.

Intervention & Design: This is a randomized, double-blind, placebo-controlled trial conducted across multiple hospitals. Approximately 360 eligible patients with advanced ovarian cancer and significant insomnia will be enrolled.

Participants will be randomly assigned to one of two groups for the initial 18-week phase:

Experimental Group: Receives the Tiaoshen Anti-cancer herbal formula granules plus standard Cognitive Behavioral Therapy for Insomnia (CBT-I).

Control Group: Receives inactive placebo granules plus the same standard CBT-I. Neither the participants nor their treating doctors will know which granules are assigned during this phase. The primary goal is to compare the improvement in sleep quality between the two groups. Key secondary goals include assessing the therapy's impact on patients' anxiety, depression, overall quality of life, and the length of time before the cancer progresses (progression-free survival). All patients will receive standard-of-care chemotherapy.

This clinical trial investigates a novel integrative approach for managing cancer-related insomnia in advanced ovarian cancer. Targeting a prevalent yet under-addressed issue affecting over 60% of patients, the study evaluates the synergistic effect of combining the Tiaoshen Anti-cancer Protocol, a patented Traditional Chinese Medicine formula, with standard Cognitive Behavioral Therapy for Insomnia (CBT-I). In this multicenter, randomized, double-blind, placebo-controlled trial, approximately 360 patients with FIGO stage III-IV ovarian cancer and clinically significant insomnia will be randomized to receive either active Tiaoshen herbal granules or matched placebo for 18 weeks, with both groups concurrently receiving structured CBT-I. The co-primary endpoints are the improvement in sleep quality, measured by the Pittsburgh Sleep Quality Index response rate, and progression-free survival. Secondary objectives include assessing impacts on anxiety, depression, quality of life, and exploring predictive biomarkers. The study employs a two-stage adaptive design, where initial responders may be re-randomized to evaluate the added benefit of a mind-body exercise in a maintenance phase. This research aims to provide high-level evidence for a holistic strategy to break the "insomnia-progression" cycle, ultimately seeking to improve both quality of life and survival outcomes.

Inclusion Criteria:

1. Patients aged 18 to 80 years (inclusive).
2. Performance status (PS) score of 0-2.
3. Histologically or cytologically confirmed primary epithelial ovarian carcinoma, with postoperative FIGO stage III-IV, and scheduled to receive postoperative standard first-line platinum-based chemotherapy.
4. Having undergone ovarian cancer debulking surgery, in a stable condition at enrollment (no active infection, no severe hepatic or renal impairment, etc.), and planned for postoperative first-line platinum-based chemotherapy.
5. Meeting the diagnostic criteria for ovarian cancer-related insomnia (difficulty initiating sleep, sleep maintenance disturbance [nocturnal awakening ≥2 times], early morning awakening with inability to return to sleep, occurring ≥3 times per week and lasting ≥1 month).
6. Possess the ability to comprehend assessment scales and undergo Cognitive Behavioral Therapy for Insomnia (e.g., Mini-Mental State Examination score ≥24, or education level above primary school).
7. Voluntarily sign the informed consent form, agree to receive the study treatment, and able to independently complete a sleep diary.

Exclusion Criteria:

1. Previous systematic treatment with Cognitive Behavioral Therapy for Insomnia.
2. History of chronic insomnia, depression, or other psychiatric disorders prior to ovarian cancer diagnosis, AND with a Patient Health Questionnaire-9 score ≥15 and a Generalized Anxiety Disorder-7 score ≥15, AND long-term use of hypnotic or psychotropic medications.
3. Pregnant or lactating women.
4. Comorbid severe primary diseases of the cardiovascular, cerebrovascular, pulmonary, hepatic, renal, or hematopoietic systems.
5. Language barriers that would prevent completion of assessments or therapy.
6. Comorbid autoimmune diseases, congenital or acquired immunodeficiency diseases, hematological diseases, or long-term use of corticosteroids or immunosuppressants.
7. Active hepatitis B, active tuberculosis, or other severe or uncontrolled infectious diseases.
8. History of chronic alcohol dependence.
9. Concurrent other primary malignant tumors (except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, etc.).
10. Participation in any other clinical trial within 3 months prior to enrollment.
11. Legally incompetent, or any medical or ethical reason that may hinder the continuation of the study.