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

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

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).

Study Overview

• Status: Completed
• Conditions: Leiomyoma
• Intervention / Treatment: Drug: TSD

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hong Kong, China, 852
    • School of Chinese Medicine, University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 52 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Premenopausal women aged 18 to 52 years; and
2. have a primary diagnosis of symptomatic UFs based on clinical symptoms; and
3. MRI examination as defined in the International Classification of Diseases (10th edition).

Exclusion Criteria:

1. Unstable medical conditions such as serious cardiovascular diseases;
2. With severe neuropsychiatric disorders;
3. Combined with adenomyosis or other tumors;
4. On treatment with Chinese medicine or other natural products in the previous 3 months;
5. With an allergic history of herbal medicine; or
6. Being pregnant and lactating women and those who currently use contraception.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose TSD; Subjects in this arm receive high dose (217 g/day) TSD for 16 weeks.	Drug: TSD; 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.; Other Names: Tumor-shrinking Decoction, Chinese medicine preparation
Active Comparator: Low dose TSD; Subjects in this arm receive low dose (69 g/day) TSD for 16 weeks.	Drug: TSD; 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.; Other Names: Tumor-shrinking Decoction, Chinese medicine preparation

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Serious and Non-Serious Adverse Events	Adverse events will be closely monitored at each visit. All adverse events, reported, elicited or observed, will be recorded on case report form, including the date and time of onset, duration, severity, relationship to study drug, and action taken.	Up to 6 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Wei Meng, The University of Hong Kong

Publications and helpful links

General Publications

• Lu J, Meng W. Clinical observation 45 cases of Yiqi Huayu treatment for uterine fibroids. Gansu TCM. 2008a;6:44-46
• Lu J, Meng W. Clinical Observation of " Hualiu Recipe" in Treating 302 Cases of Hysteromyoma with Qi- Deficiency and Blood- Stasis Syndrome. Shanghai Traditional Chinese Medicine. 2008b;3:49-51
• Meng W, Ma B. Three drugs on cultured uterine leiomyoma cell proliferation and apoptosis, and regulatory factors. Traditional Chinese. 2003;21:2046-2048
• Meng W. Zhao W. Effects of methods of invigorating qi and dissolving stasis on the expression of proliferating and apoptosis of cultured human uterine leiomyoma cells. Chinese archives of traditional Chinese medicine. 2008(2);238-240
• Tan L, Meng W, Zhang TT. [Predisposing factors of hysteromyoma and effect of hualiu recipe on it]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2011 May;31(5):635-8. Chinese.

Helpful Links

• American Society of Reproductive Medicine Patient Booklet: Uterine Fibroids

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: May 14, 2014
• First Submitted That Met QC Criteria: July 10, 2014
• First Posted (Estimate): July 14, 2014

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 27, 2020
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Leiomyoma; Medicine, Chinese Traditional
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma
• Other Study ID Numbers: HKU-SCM-TSD2014; HMRF-11121841 (Other Grant/Funding Number: Health and Medical Research Fund (HMRF))