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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep Initiation and Maintenance Disorders; Chinese Herbal Medicine; Cognitive Behavioral Therapy; Medicine, Chinese Traditional; Ovarian Neoplasms Malignant
• Intervention / Treatment: Drug: Tiaoshen Anti-cancer Granules; Behavioral: Cognitive Behavioral Therapy for Insomnia; Other: Standard First-line Platinum-based Chemotherapy; Drug: Placebo Granules; Behavioral: Sleep-Regulating Daoyin Exercises; Other: Standard Maintenance Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jianhui Tian, M.D.; Phone Number: 86+18917763382; Email: tjhhawk@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200071
      • Shanghai Hospital of Traditional Chinese Medicine
      • Contact: Jianhui Tian; Phone Number: 86+18917763382; Email: tjhhawk@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiaoshen Granules + CBT-I Group	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, membrane separation, and spray drying) with a full-chain quality control system (including fingerprint chromatography) to ensure inter-batch consistency, stability, and safety. For the trial, both the active granules and a matched placebo (simulant containing only 5% of the active ingredient) are produced to be identical in appearance, smell, and packaging for the double-blind, placebo-controlled first phase.; 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 Control Therapy, Cognitive Restructuring (challenging catastrophizing thoughts such as "insomnia will inevitably cause cancer recurrence"), sleep hygiene education tailored for cancer patients, and relaxation training. It is delivered by certified therapists who have undergone protocol-specific training and receive regular supervision to ensure fidelity.; 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 plus Carboplatin, among others. The specific drug choice and dosage are determined by the treating oncologist according to guidelines and individual patient conditions, independent of the study group assignment.
Placebo Comparator: Placebo + CBT-I Grou	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 Control Therapy, Cognitive Restructuring (challenging catastrophizing thoughts such as "insomnia will inevitably cause cancer recurrence"), sleep hygiene education tailored for cancer patients, and relaxation training. It is delivered by certified therapists who have undergone protocol-specific training and receive regular supervision to ensure fidelity.; 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 plus Carboplatin, among others. The specific drug choice and dosage are determined by the treating oncologist according to guidelines and individual patient conditions, independent of the study group assignment.; 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 Tianjiang Pharmaceutical Co., Ltd.) using the same excipients and packaging processes to guarantee sensory indistinguishability, thereby enabling an objective evaluation of the true efficacy of the active drug.
Experimental: Tiaoshen Granules + Daoyin Group	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, membrane separation, and spray drying) with a full-chain quality control system (including fingerprint chromatography) to ensure inter-batch consistency, stability, and safety. For the trial, both the active granules and a matched placebo (simulant containing only 5% of the active ingredient) are produced to be identical in appearance, smell, and packaging for the double-blind, placebo-controlled first phase.; 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 posture, including pushing the arms forward and upward, leaning forward to massage the feet, and rubbing the hands to warm the kidney area, with an emphasis on the coordination of movement, breath, and mental focus. Practice is instructed by qualified Daoyin lecturers trained uniformly for the project, with adherence and accuracy ensured through instructional videos and practice logging.; 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 Chinese medicine alone). Specific regimens typically involve oral PARP inhibitors (e.g., Olaparib, Niraparib) or Bevacizumab. The specific drug choice and dosage are independently determined by the treating oncologist according to guidelines and the patient's profile.
Active Comparator: Tiaoshen Granules Only Group	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, membrane separation, and spray drying) with a full-chain quality control system (including fingerprint chromatography) to ensure inter-batch consistency, stability, and safety. For the trial, both the active granules and a matched placebo (simulant containing only 5% of the active ingredient) are produced to be identical in appearance, smell, and packaging for the double-blind, placebo-controlled first phase.; 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 Chinese medicine alone). Specific regimens typically involve oral PARP inhibitors (e.g., Olaparib, Niraparib) or Bevacizumab. The specific drug choice and dosage are independently determined by the treating oncologist according to guidelines and the patient's profile.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSQI Response Rate	The proportion of subjects with a reduction of ≥ 50% in the total Pittsburgh Sleep Quality Index score from baseline. PSQI is a standardized scale assessing sleep quality, with higher scores indicating poorer sleep quality.	Baseline, Week 18
Progression-Free Survival	The time from randomization until the first observation of disease progression (according to RECIST 1.1 criteria) or death from any cause, whichever occurs first.	From randomization, assessed continuously up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-Year Progression-Free Survival Rate	The proportion of subjects alive and free from disease progression at 1 year after randomization.	1 year after randomization
2-Year Progression-Free Survival Rate	The proportion of subjects alive and free from disease progression at 2 years after randomization.	2 years after randomization
Time to First Subsequent Therapy	The time from the permanent discontinuation of the current (first-line) therapy to the initiation date of the next anti-cancer therapy.	From the end of first-line therapy, assessed until start of second-line therapy or death (up to 2 years)
Chemotherapy Completion Rate	The proportion of subjects who complete ≥ 75% of the planned (6-8 cycles) first-line platinum-based chemotherapy cycles.	During the first-line chemotherapy phase (approximately within 18 weeks)
Change in Patient Health Questionnaire-9 Score	A 9-item scale used to assess the severity of depressive symptoms. Total scores range from 0 to 27, with higher scores indicating greater severity of depression.	Baseline, Weeks 3, 6, 9, 12, 15, 18, 22, 26
Change in Generalized Anxiety Disorder-7 Score	A 7-item scale used to assess the severity of anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating greater severity of anxiety.	Baseline, Weeks 3, 6, 9, 12, 15, 18, 22, 26
Change in EORTC QLQ-C30 Score	The EORTC QLQ-C30 is a core quality-of-life questionnaire developed by the European Organisation for Research and Treatment of Cancer. It consists of multiple subscales: global health status (range 0-100), functional domains (physical, role, emotional, cognitive, social; each range 0-100), and symptom domains (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea; each range 0-100). For the global health status and functional subscales, higher scores indicate better quality of life and functioning (better outcome). For the symptom subscales, higher scores indicate more severe symptoms (worse outcome). Each subscale will be analyzed separately as a continuous variable.	Baseline, Weeks 6, 12, 18, 22, 26
Change in TCM Syndrome Score	The Traditional Chinese Medicine (TCM) Symptom Score is a scale developed according to the "Shanghai TCM Disease Diagnosis and Treatment Routine." It assesses 7 core symptoms (difficulty falling asleep, light sleep with easy awakening, dream-disturbed sleep and early awakening, fatigue and weakness, irritability, palpitations and forgetfulness, dry mouth and throat), each scored from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). The total score ranges from 0 to 21. Higher scores indicate more severe TCM symptoms, representing worse outcomes.	Baseline, Weeks 6, 12, 18, 22, 26

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of Predictive Biomarkers	Exploration of biomarkers associated with response to the "Tiaoshen" protocol (e.g., immune cell subsets, metabolites, HPA-axis related hormones) using multi-omics technologies (e.g., single-cell sequencing, metabolomics) on blood and (if accessible) tissue samples collected pre- and post-treatment.	Baseline, Week 18
Performance of AI Efficacy Prediction Model	Evaluate the accuracy (e.g., Area Under the Curve) of an artificial intelligence prediction model built on clinical multimodal data (demographics, lab tests, scale scores, etc.) in predicting patient PSQI response rate and progression-free survival.	Up to 30 months.

Collaborators and Investigators

• Sponsor: Shanghai Municipal Hospital of Traditional Chinese Medicine
• Collaborators: Fudan University; Shanghai Mental Health Center; Obstetrics & Gynecology Hospital of Fudan University; The First Affiliated Hospital of Naval Medical University
• Investigators: Study Chair: Jianhui Tian, Shanghai Hospital of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: March 21, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Ovarian Cancer; Traditional Chinese Medicine; Cognitive Behavioral Therapy for Insomnia; Progression-Free Survival; Cancer-Related Insomnia
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Nervous System Diseases; Mental Disorders; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Sleep Wake Disorders; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Ovarian Neoplasms; Sleep Initiation and Maintenance Disorders; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy
• Other Study ID Numbers: 25Y12800600

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared outside the primary research team at this stage. The study involves a proprietary TCM formula (Mind-Regulating Cancer Treatment Protocol) and a unique integrative intervention. Premature data sharing could compromise pending patents and ongoing mechanistic studies. The dataset includes multimodal information (clinical scales, TCM syndrome evaluations, multi-omics, AI data). Accurate interpretation requires domain expertise; premature release risks misinterpretation. The ethics-approved informed consent did not include broad data sharing provisions. Therefore, IPD will not be publicly available. However, de-identified data supporting primary/secondary outcomes may be available upon reasonable request to the corresponding author after main results are published, subject to a formal data use agreement and ethics approval.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No