Study of Tumor-shrinking Decoction (TSD) to Treat Symptomatic Uterine Fibroids

Study Overview
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Brief Summary
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On the basis of empirical evidence and clinical practice, the investigators have developed a formula called Tumor-shrinking Decoction (TSD) used in the treatment of uterine fibroids (UFs). The investigators preliminary clinical observation has demonstrated the benefits of TSD in improving UFs. TSD is composed of 15 individual Chinese medicines: Astragalus Membranaceus, Semen Coicis, Poria, Curcuma longa L, and Fritillaria Thunbergii Miq, Cassia twig, Pollen typhae, Resina draconis, Lithospermum erythrorhizon, Halloysitum Rubrum, Rhizoma Corydalis processed with vinegar, Hirudo, Calcined corrugated sub , Oyster Shell and Laminaria Japonica Aresch. It is hypothesized that TSD can effectively reduce the fibroid size and improve the symptoms associated with UFs and the greater anti-tumor potency of TSD is associated with higher therapeutic doses. To test this hypothesis, one 16-week, double-blind, randomized, two-dose trial will be conducted in patients with symptomatic UFs to determine whether the high dose (217 g/day) of TSD could produce significantly greater effects in reducing the fibroid size and improving its related symptoms and biochemical profiles compared to the lower dose (69 g/day).

Detailed Description
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Numerous Chinese medicine preparations have been shown to possess therapeutic potential in relieving uterine fibroids (UFs) symptoms and shrinking the volume of fibroids without significant adverse effects, although the clinical efficacy needs to be further confirmed with rigorously designed.On the basis of empirical evidence and clinical practice, the investigators have developed a formula called Tumor-shrinking Decoction (TSD) used in the treatment of UFs. The investigators preliminary clinical observation has demonstrated the benefits of TSD in improving UFs. TSD is composed of 15 individual Chinese medicines. According to traditional Chinese medicine (TCM) doctrine, most UFs are developed due to the deficiency of vital energy and the stasis of blood, resulting in the formation of pathological massive tissues. Individual Chinese medicines constituting TSD can be classified into three classes based on TCM-defined pharmacological actions: (i) Tonifying qi and resolve phlegm: Astragalus Membranaceus, Semen Coicis, Poria, Curcuma longa L, and Fritillaria Thunbergii Miq; (ii) Resolve stasis, stopping bleeding and relieve pain: Cassia twig, Pollen typhae, Resina draconis, Lithospermum erythrorhizon, Halloysitum Rubrum, Rhizoma Corydalis processed with vinegar; and (iii) Softening hardness and dissipate binds: Hirudo, Calcined corrugated sub , Oyster Shell and Laminaria Japonica Aresch. Indeed, the investigators previous studies of cultured cells and animals have revealed that TSD robustly inhibits fibroid cell growth and proliferation. The investigators therefore hypothesize that TSD can effectively reduce the fibroid size and improve the symptoms associated with UFs and the greater anti-tumor potency of TSD is associated with higher therapeutic doses. To test this hypothesis, one 16-week, double-blind, randomized, two-dose trial will be conducted in patients with symptomatic UFs to determine whether the high dose (217 g/day) of TSD could produce significantly greater effects in reducing the fibroid size and improving its related symptoms and biochemical profiles compared to the lower dose (69 g/day).

Official Title
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A Double-blind, Randomized, Two-dose Trial of Tumor-shrinking Decoction (TSD), a Chinese Medicine Preparation in Patients With Symptomatic Uterine Fibroids

Conditions
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Leiomyoma

Intervention / Treatment
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* Drug: TSD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal women aged 18 to 52 years; and have a primary diagnosis of symptomatic UFs based on clinical symptoms; and MRI examination as defined in the International Classification of Diseases (10th edition). Exclusion Criteria: Unstable medical conditions such as serious cardiovascular diseases; With severe neuropsychiatric disorders; Combined with adenomyosis or other tumors; On treatment with Chinese medicine or other natural products in the previous 3 months; With an allergic history of herbal medicine; or Being pregnant and lactating women and those who currently use contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 52 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose TSD<br>Subjects in this arm receive high dose (217 g/day) TSD for 16 weeks. | Drug: TSD<br>* TSD is composed of 15 individual Chinese medicines: Astragalus Membranaceus, Semen Coicis, Poria, Curcuma longa L, and Fritillaria Thunbergii Miq, Cassia twig, Pollen typhae, Resina draconis, Lithospermum erythrorhizon, Halloysitum Rubrum, Rhizoma Corydalis processed with vinegar, Hirudo, Calcined corrugated sub , Oyster Shell and Laminaria Japonica Aresch. High dose (127g) or Low dose (69g) TSD decoction boiled as 200ml per bag; 2 bags per day, 6 days per week; Orally in-take one bag of TSD decoction in morning and another in evening after meal; The whole treatment lasts for 16 weeks.<br>* Other names: Tumor-shrinking Decoction, Chinese medicine preparation;|
| Active Comparator: Low dose TSD<br>Subjects in this arm receive low dose (69 g/day) TSD for 16 weeks. | Drug: TSD<br>* TSD is composed of 15 individual Chinese medicines: Astragalus Membranaceus, Semen Coicis, Poria, Curcuma longa L, and Fritillaria Thunbergii Miq, Cassia twig, Pollen typhae, Resina draconis, Lithospermum erythrorhizon, Halloysitum Rubrum, Rhizoma Corydalis processed with vinegar, Hirudo, Calcined corrugated sub , Oyster Shell and Laminaria Japonica Aresch. High dose (127g) or Low dose (69g) TSD decoction boiled as 200ml per bag; 2 bags per day, 6 days per week; Orally in-take one bag of TSD decoction in morning and another in evening after meal; The whole treatment lasts for 16 weeks.<br>* Other names: Tumor-shrinking Decoction, Chinese medicine preparation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the symptom severity score of Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL) from Baseline to 6 months | UFS-QOL consists of 37 items to assess the severity of UFs-related symptoms and the quality of life of patients. | Baseline and once per month thereafter; Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of clinical response from baseline on the the health-related quality of life of transformed UFS-QOL score | The secondary clinical outcome is the clinical response that is defined as a ≥30% baseline-to-endpoint reduction on the symptom severity of transformed UFS-QOL score. | Baseline and once per month thereafter; Up to 6 months | 
| Imaging outcomes | Imaging outcomes will be examined at baseline and endpoint using magnetic resonance imaging (MRI) scan to determine the number, size and density of the uterine fibroids. | Baseline, 5th month | 
| Serum concentrations of estrogen and follicle-stimulating hormone | two blood samples will be collected from each patient at baseline and at the end of the study, respectively. The collection of blood will be conducted between 08:00 and 09:00 before meal. Sera will be separated and stored at -20ºC until assayed. Serum concentrations of estrogen, progesterone and follicle-stimulating hormone will be measured using chemiluminescent immunoassay (CLIA). | Baseline, 5th month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leiomyoma, Medicine, Chinese Traditional, Randomized Controlled Trial