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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug Tiaoshen Anti-cancer Granules
  This intervention is a patented herbal formula granule (Patent No.: ZL202210718678.8) for cancer-related insomnia. Based on the "Mind-Regulating and Anti-Cancer" theory of Traditional Chinese Medicine (TCM), it is composed of four herbs: Astragalus Membranaceus (30g), Paris Polyphylla (9g), Spina Date Seed (30g), and Curcuma Aromatic (9g). The granules are manufactured by Jiangyin Tianjiang Pharmaceutical Co., Ltd. using modern standardized processes (including dynamic counter-current extraction
• Drug Placebo Granules
  This control intervention is a matched simulator (placebo) for the active "Tiaoshen Anti-cancer Granules." To ensure the rigor of the double-blind design, the placebo granules are identical to the active drug granules in appearance (color, shape), properties, smell, packaging specifications, and administration method. The key distinction is that the placebo contains less than 5% of the active drug ingredients (or lacks the main active components). It is manufactured by the same company (Jiangyin
• Behavioral Cognitive Behavioral Therapy for Insomnia
  This intervention is a standardized, structured psychobehavioral therapy protocol designed according to international guidelines for cancer-related insomnia. It is not general psychological counseling but a systematically adapted protocol specifically targeting factors maintaining insomnia in cancer patients (e.g., somatic hyperarousal, cancer-related dysfunctional sleep beliefs, interference from treatment side effects). Core modules include: Sleep Restriction/Compression Therapy, Stimulus Cont
• Other Standard First-line Platinum-based Chemotherapy
  This intervention refers to the established standard first-line systemic chemotherapy regimen for postoperative patients with FIGO stage III-IV epithelial ovarian cancer, as per contemporary international authoritative clinical guidelines (e.g., CSCO, NCCN). It is not an investigational intervention of this study but the foundational anti-cancer treatment required for all enrolled patients. Specific regimens may include Paclitaxel plus Carboplatin, Nab-paclitaxel plus Carboplatin, or Docetaxel p
• Behavioral Sleep-Regulating Daoyin Exercises
  This intervention is a standardized Traditional Chinese Medicine (TCM) Daoyin rehabilitation exercise derived from the national intangible cultural heritage, "Guben Yijin Jing Twelve Postures Daoyin Method." It is not general physical exercise or calisthenics but a seated mind-body regulation technique designed based on TCM theory for insomnia attributed to "disconnection between the heart and mind." The standardized procedure involves a series of gentle movements performed in a specific sitting
• Other Standard Maintenance Therapy
  This intervention refers to the established standard maintenance therapy administered after completing first-line platinum-based chemotherapy, based on the patient's genetic test results (e.g., BRCA mutation, HRD status) and recommendations from clinical guidelines (e.g., CSCO, NCCN). It is not an investigational intervention of this study but the conventional anti-cancer treatment that patients in the second phase receive concurrently with the study-specific interventions (Daoyin exercises or C

Primary outcome measures

• PSQI Response Rate [Time frame: Baseline, Week 18]
• Progression-Free Survival [Time frame: From randomization, assessed continuously up to 2 years]

Secondary outcome measures (8)

• 1-Year Progression-Free Survival Rate [Time frame: 1 year after randomization]
• 2-Year Progression-Free Survival Rate [Time frame: 2 years after randomization]
• Time to First Subsequent Therapy [Time frame: From the end of first-line therapy, assessed until start of second-line therapy or death (up to 2 years)]
• Chemotherapy Completion Rate [Time frame: During the first-line chemotherapy phase (approximately within 18 weeks)]
• Change in Patient Health Questionnaire-9 Score [Time frame: Baseline, Weeks 3, 6, 9, 12, 15, 18, 22, 26]
• Change in Generalized Anxiety Disorder-7 Score [Time frame: Baseline, Weeks 3, 6, 9, 12, 15, 18, 22, 26]
• Change in EORTC QLQ-C30 Score [Time frame: Baseline, Weeks 6, 12, 18, 22, 26]
• Change in TCM Syndrome Score [Time frame: Baseline, Weeks 6, 12, 18, 22, 26]

Eligibility criteria

Inclusion criteria

• Patients aged 18 to 80 years (inclusive).
• Performance status (PS) score of 0-2.
• 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.
• 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.
• 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).
• 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).
• Voluntarily sign the informed consent form, agree to receive the study treatment, and able to independently complete a sleep diary.

Exclusion criteria

• Previous systematic treatment with Cognitive Behavioral Therapy for Insomnia.
• 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.
• Pregnant or lactating women.
• Comorbid severe primary diseases of the cardiovascular, cerebrovascular, pulmonary, hepatic, renal, or hematopoietic systems.
• Language barriers that would prevent completion of assessments or therapy.
• Comorbid autoimmune diseases, congenital or acquired immunodeficiency diseases, hematological diseases, or long-term use of corticosteroids or immunosuppressants.
• Active hepatitis B, active tuberculosis, or other severe or uncontrolled infectious diseases.
• History of chronic alcohol dependence.
• Concurrent other primary malignant tumors (except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, etc.).
• Participation in any other clinical trial within 3 months prior to enrollment.
• Legally incompetent, or any medical or ethical reason that may hinder the continuation of the study.

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 · 1 center

• Shanghai Hospital of Traditional Chinese Medicine — Shanghai

Identifiers

NCT: NCT07550205 · 25Y12800600

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗