<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02189083</url>
  </required_header>
  <id_info>
    <org_study_id>HKU-SCM-TSD2014</org_study_id>
    <secondary_id>HMRF-11121841</secondary_id>
    <nct_id>NCT02189083</nct_id>
  </id_info>
  <brief_title>Study of Tumor-shrinking Decoction (TSD) to Treat Symptomatic Uterine Fibroids</brief_title>
  <official_title>A Double-blind, Randomized, Two-dose Trial of Tumor-shrinking Decoction (TSD), a Chinese Medicine Preparation in Patients With Symptomatic Uterine Fibroids</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      On the basis of empirical evidence and clinical practice, the investigators have developed a&#xD;
      formula called Tumor-shrinking Decoction (TSD) used in the treatment of uterine fibroids&#xD;
      (UFs). The investigators preliminary clinical observation has demonstrated the benefits of&#xD;
      TSD in improving UFs.&#xD;
&#xD;
      TSD is composed of 15 individual Chinese medicines: Astragalus Membranaceus, Semen Coicis,&#xD;
      Poria, Curcuma longa L, and Fritillaria Thunbergii Miq, Cassia twig, Pollen typhae, Resina&#xD;
      draconis, Lithospermum erythrorhizon, Halloysitum Rubrum, Rhizoma Corydalis processed with&#xD;
      vinegar, Hirudo, Calcined corrugated sub , Oyster Shell and Laminaria Japonica Aresch.&#xD;
&#xD;
      It is hypothesized that TSD can effectively reduce the fibroid size and improve the symptoms&#xD;
      associated with UFs and the greater anti-tumor potency of TSD is associated with higher&#xD;
      therapeutic doses.&#xD;
&#xD;
      To test this hypothesis, one 16-week, double-blind, randomized, two-dose trial will be&#xD;
      conducted in patients with symptomatic UFs to determine whether the high dose (217 g/day) of&#xD;
      TSD could produce significantly greater effects in reducing the fibroid size and improving&#xD;
      its related symptoms and biochemical profiles compared to the lower dose (69 g/day).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous Chinese medicine preparations have been shown to possess therapeutic potential in&#xD;
      relieving uterine fibroids (UFs) symptoms and shrinking the volume of fibroids without&#xD;
      significant adverse effects, although the clinical efficacy needs to be further confirmed&#xD;
      with rigorously designed.On the basis of empirical evidence and clinical practice, the&#xD;
      investigators have developed a formula called Tumor-shrinking Decoction (TSD) used in the&#xD;
      treatment of UFs. The investigators preliminary clinical observation has demonstrated the&#xD;
      benefits of TSD in improving UFs.&#xD;
&#xD;
      TSD is composed of 15 individual Chinese medicines. According to traditional Chinese medicine&#xD;
      (TCM) doctrine, most UFs are developed due to the deficiency of vital energy and the stasis&#xD;
      of blood, resulting in the formation of pathological massive tissues. Individual Chinese&#xD;
      medicines constituting TSD can be classified into three classes based on TCM-defined&#xD;
      pharmacological actions: (i) Tonifying qi and resolve phlegm: Astragalus Membranaceus, Semen&#xD;
      Coicis, Poria, Curcuma longa L, and Fritillaria Thunbergii Miq; (ii) Resolve stasis, stopping&#xD;
      bleeding and relieve pain: Cassia twig, Pollen typhae, Resina draconis, Lithospermum&#xD;
      erythrorhizon, Halloysitum Rubrum, Rhizoma Corydalis processed with vinegar; and (iii)&#xD;
      Softening hardness and dissipate binds: Hirudo, Calcined corrugated sub , Oyster Shell and&#xD;
      Laminaria Japonica Aresch.&#xD;
&#xD;
      Indeed, the investigators previous studies of cultured cells and animals have revealed that&#xD;
      TSD robustly inhibits fibroid cell growth and proliferation. The investigators therefore&#xD;
      hypothesize that TSD can effectively reduce the fibroid size and improve the symptoms&#xD;
      associated with UFs and the greater anti-tumor potency of TSD is associated with higher&#xD;
      therapeutic doses.&#xD;
&#xD;
      To test this hypothesis, one 16-week, double-blind, randomized, two-dose trial will be&#xD;
      conducted in patients with symptomatic UFs to determine whether the high dose (217 g/day) of&#xD;
      TSD could produce significantly greater effects in reducing the fibroid size and improving&#xD;
      its related symptoms and biochemical profiles compared to the lower dose (69 g/day).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in the symptom severity score of Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL) from Baseline to 6 months</measure>
    <time_frame>Baseline and once per month thereafter; Up to 6 months</time_frame>
    <description>UFS-QOL consists of 37 items to assess the severity of UFs-related symptoms and the quality of life of patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of clinical response from baseline on the the health-related quality of life of transformed UFS-QOL score</measure>
    <time_frame>Baseline and once per month thereafter; Up to 6 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Imaging outcomes</measure>
    <time_frame>Baseline, 5th month</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of estrogen and follicle-stimulating hormone</measure>
    <time_frame>Baseline, 5th month</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>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.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Leiomyoma</condition>
  <arm_group>
    <arm_group_label>High dose TSD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm receive high dose (217 g/day) TSD for 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low dose TSD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in this arm receive low dose (69 g/day) TSD for 16 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TSD</intervention_name>
    <description>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.&#xD;
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.</description>
    <arm_group_label>High dose TSD</arm_group_label>
    <arm_group_label>Low dose TSD</arm_group_label>
    <other_name>Tumor-shrinking Decoction, Chinese medicine preparation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Premenopausal women aged 18 to 52 years; and&#xD;
&#xD;
          2. have a primary diagnosis of symptomatic UFs based on clinical symptoms; and&#xD;
&#xD;
          3. MRI examination as defined in the International Classification of Diseases (10th&#xD;
             edition).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unstable medical conditions such as serious cardiovascular diseases;&#xD;
&#xD;
          2. With severe neuropsychiatric disorders;&#xD;
&#xD;
          3. Combined with adenomyosis or other tumors;&#xD;
&#xD;
          4. On treatment with Chinese medicine or other natural products in the previous 3 months;&#xD;
&#xD;
          5. With an allergic history of herbal medicine; or&#xD;
&#xD;
          6. Being pregnant and lactating women and those who currently use contraception.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>52 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Meng</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>School of Chinese Medicine, University of Hong Kong</name>
      <address>
        <city>Hong Kong</city>
        <zip>852</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.asrm.org/FactSheetsandBooklets/</url>
    <description>American Society of Reproductive Medicine Patient Booklet: Uterine Fibroids</description>
  </link>
  <results_reference>
    <citation>Lu J, Meng W. Clinical observation 45 cases of Yiqi Huayu treatment for uterine fibroids. Gansu TCM. 2008a;6:44-46</citation>
  </results_reference>
  <results_reference>
    <citation>Lu J, Meng W. Clinical Observation of &quot; Hualiu Recipe&quot; in Treating 302 Cases of Hysteromyoma with Qi- Deficiency and Blood- Stasis Syndrome. Shanghai Traditional Chinese Medicine. 2008b;3:49-51</citation>
  </results_reference>
  <results_reference>
    <citation>Meng W, Ma B. Three drugs on cultured uterine leiomyoma cell proliferation and apoptosis, and regulatory factors. Traditional Chinese. 2003;21:2046-2048</citation>
  </results_reference>
  <results_reference>
    <citation>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</citation>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>21812264</PMID>
  </results_reference>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>May 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>October 27, 2020</last_update_submitted>
  <last_update_submitted_qc>October 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Leiomyoma</keyword>
  <keyword>Medicine, Chinese Traditional</keyword>
  <keyword>Randomized Controlled Trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leiomyoma</mesh_term>
    <mesh_term>Myofibroma</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02189083
org study id: HKU-SCM-TSD2014
secondary id: HMRF-11121841
nct id: NCT02189083
lead sponsor: 
has dmc: Yes
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).
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in the symptom severity score of Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL) from Baseline to 6 months
time frame: Baseline and once per month thereafter; Up to 6 months
description: UFS-QOL consists of 37 items to assess the severity of UFs-related symptoms and the quality of life of patients.
measure: Change of clinical response from baseline on the the health-related quality of life of transformed UFS-QOL score
time frame: Baseline and once per month thereafter; Up to 6 months
description: 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.
measure: Imaging outcomes
time frame: Baseline, 5th month
description: 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.
measure: Serum concentrations of estrogen and follicle-stimulating hormone
time frame: Baseline, 5th month
description: 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).
measure: Number of Participants with Serious and Non-Serious Adverse Events
time frame: Up to 6 months
description: 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.
arm group label: High dose TSD
arm group type: Experimental
description: Subjects in this arm receive high dose (217 g/day) TSD for 16 weeks.
arm group label: Low dose TSD
arm group type: Active Comparator
description: Subjects in this arm receive low dose (69 g/day) TSD for 16 weeks.
intervention type: Drug
intervention name: TSD
description: 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.
arm group label: High dose TSD
arm group label: Low dose TSD
other name: Tumor-shrinking Decoction, Chinese medicine preparation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 52 Years
healthy volunteers: No
last name: Wei Meng
role: Principal Investigator
affiliation: The University of Hong Kong
facility: 
country: China
url: http://www.asrm.org/FactSheetsandBooklets/
description: American Society of Reproductive Medicine Patient Booklet: Uterine Fibroids
citation: Lu J, Meng W. Clinical observation 45 cases of Yiqi Huayu treatment for uterine fibroids. Gansu TCM. 2008a;6:44-46
citation: 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
citation: Meng W, Ma B. Three drugs on cultured uterine leiomyoma cell proliferation and apoptosis, and regulatory factors. Traditional Chinese. 2003;21:2046-2048
citation: 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
citation: 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.
PMID: 21812264
responsible party type: Sponsor
mesh term: Leiomyoma
mesh term: Myofibroma