<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/NCT04457531</url>
  </required_header>
  <id_info>
    <org_study_id>LIUWEI-V1.1</org_study_id>
    <nct_id>NCT04457531</nct_id>
  </id_info>
  <brief_title>LiuWeiLuoBi Granule for the Treatment of Diabetic Peripheral Neuropathy</brief_title>
  <official_title>A Randomized Controlled Study of LiuWeiLuoBi Granule for the Treatment of Diabetic Peripheral Neuropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Academy of Chinese Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Academy of Chinese Medical Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Based on network pharmacology, Liuweiluobi Granule was screened to treat diabetes peripheral&#xD;
      neuropathy with deficiency of the spleen and kidney and stasis-heat syndrome.In the&#xD;
      preliminary animal experiment, it suggested that this granule had a significant protective&#xD;
      effect on the peripheral motor nerves of diabetic peripheral neuropathy and the effect of&#xD;
      anti-inflammation, and the prescription did not induce the death of zebrafish at a&#xD;
      concentration of 1000 ug/mL, without any obvious toxicity. This study aims to evaluate the&#xD;
      efficacy of Liuweiluobi Granule in improving neurotransmission function in patients with&#xD;
      diabetic peripheral neuropathy through a pilot, randomized controlled study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 26, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Early Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean maximal nerve conduction velocity</measure>
    <time_frame>12 weeks</time_frame>
    <description>Mean maximal conduction velocity of the common peroneal motor nerve (MCV) and sensory nerve (SCV)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Michigan Diabetic Peripheral Neuropathy Score (MDNS)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Michigan Diabetic Peripheral Neuropathy Score (MDNS) is a 46 point clinical score, with score ranging from 0 to 3 (score of 0, normal; 1, mild to moderate; 2, severe and score of 3, absent). The score is more high means a worse outcome.In MDNS vibration, pain, and light touch are assessed with a 128 Hz tuning fork, a pin, and a 10g filament, respectively. The outcome measures were performed by the investigator at baseline and at the eighth week.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toronto clinical scoring system (TCSS)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Toronto clinical scoring system (TCSS) includes three parts: the symptom score of the symptom, the reflection score of the nerve and the evaluation score of the sensory function test. Symptoms include numbness, pain, and needle-like sensation in the lower extremities Feelings of weakness, weakness, instability in walking, and similar symptoms of the upper limbs, such as normal score of 0, 1 point for the presence of corresponding symptoms, a total of 6 points; nerve reflex including ankle reflex and knee reflex, bilateral score, normal score of 0, weakened 1 point, 2 points for disappearance, 8 points in total; sensory function test includes 5 items of pain, temperature, pressure, vibration, and position on the right big toe, 0 points for normal, 1 point for abnormality, 5 points in total With a total score of 19 points. With a score of 0 to 5 do not exist in the DPN, 6 to 8 are mild DPN, 9 to 11 are moderate DPN, 12 to 19 are severe DPN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative symptoms scales of DPN in Traditional Chinese medicine</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the level of aldose reductase</measure>
    <time_frame>to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting blood glucose</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2 hrs postprandial blood glucose</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total lipids (TC)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Lipid level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>triglycerides (TG)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Lipid level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>high density lipoprotein cholesterol (HDL-C)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Lipid level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>low density lipid Protein cholesterol (LDL-C).</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Lipid level</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Amino acids, lipid metabolites, vitamins, neurotransmitters and other metabolites</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks and 12 weeks</time_frame>
    <description>Amino acids, lipid metabolites, vitamins, neurotransmitters and other metabolites will be analyzed and tested using targeted metabolic analysis.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Diabetic Peripheral Neuropathy</condition>
  <condition>Chinese Medicine</condition>
  <condition>Nerve Conduction</condition>
  <arm_group>
    <arm_group_label>LiuWeiLuoBi Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive the treatment of LiuWeiLuoBi Granule for 12 weeks,twice a day added to the standard medical treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients will receive the standard medical treatment for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LiuWeiLuoBi Granule</intervention_name>
    <description>LiuWeiLuoBi Granule is a Chinese medicine made from 6 herbal medicine, including Shaji(Sea-buckthorn), Honghua (Safflower), Jinyinhua(Honeysuckle),etc.</description>
    <arm_group_label>LiuWeiLuoBi Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard medical treatment</intervention_name>
    <description>Standard medical therapy is adhered to the guidline issued by American Diabetes Association and Chinese Diabetes Society at 2017, including keeping an appropriate diet, doing some exercises, the pharmacological therapy to control the blood glucose, blood pressure and blood lipids.</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>LiuWeiLuoBi Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Meet the clinical confirmed diagnostic criteria of &quot;diabetic peripheral neuropathy&quot;;&#xD;
&#xD;
          2. Toronto score ≥ 6 points;&#xD;
&#xD;
          3. Meet the Chinese medicine diagnostic criteria of Pi-Shen-Liang-Xu (Deficiency of Pi&#xD;
             and Shen) and Yu-Re-Ru-Luo (Collaterals with Stasis and Heat） Zheng (Syndrome) in&#xD;
             diabetic peripheral neuropathy;&#xD;
&#xD;
          4. Over 18 years old and under 75 years old, regardless of gender and ethnicity;&#xD;
&#xD;
          5. Have received basic treatment for diabetes controled with stable blood glucose level&#xD;
             (fasting blood glucose: &lt;7mmol / L; 2h postprandial blood glucose: &lt;11.1mmol / L;&#xD;
             glycated hemoglobin: &lt;8%);&#xD;
&#xD;
          6. Have not taken or stopped taking DPN-related drugs (Mutan granules, Qidan Tongluo&#xD;
             granules, pregabalin, duloxetine, etc.) for more than one week;&#xD;
&#xD;
          7. Sign the informed consent form with valid telephone contact information.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Patients with diabetic ketosis, ketoacidosis or co-infection;&#xD;
&#xD;
          2. Patients with known malignant tumors;&#xD;
&#xD;
          3. Patients with known severe brain diseases, as cerebral infactions with limited&#xD;
             activity；&#xD;
&#xD;
          4. Patients with known severe arrhythmias or heart failure over Grade 2 (New York Heart&#xD;
             Association), or other known severe heart diseases;&#xD;
&#xD;
          5. Patients with known severe kidney impairment (creatinine ≥200ummol/L);&#xD;
&#xD;
          6. During the screening or within 24 hours before screening, patients were found to have&#xD;
             any of the following laboratory parameter abnormalities (based on local laboratory&#xD;
             reference range):-ALT and/or AST level&gt; 2 times the upper limit of normal range (ULN);&#xD;
&#xD;
          7. Patients with spinal cord injury, cervical and lumbar spine lesions (nervous root&#xD;
             compression, spinal stenosis, cervical and lumbar degenerative lesions) or sequelae of&#xD;
             cerebrovascular disease, neuromuscular junction or muscle disease;&#xD;
&#xD;
          8. Patients with other neuropathy diseases caused by, such as: cerebral infarction,&#xD;
             Guillain-Barre syndrome, severe arteriovenous vascular disease (venous embolism,&#xD;
             lymphangitis), chronic inflammatory demyelinating polyneuropathy, VitB Deficiency,&#xD;
             hypothyroidism, alcoholism, neurotoxicity indused by chemotherapeutic drugs, or&#xD;
             metabolic nerve damage caused by renal insufficiency;&#xD;
&#xD;
          9. Patients with severe arteriovenous vascular disease (venous embolism, lymphangitis,&#xD;
             etc.);&#xD;
&#xD;
         10. Patients with epilepsy or mental illness;&#xD;
&#xD;
         11. Alcoholics;&#xD;
&#xD;
         12. Patients with a history of psychotropic substance abuse;&#xD;
&#xD;
         13. Patients with allergies or allergies to any drugs in the trial;&#xD;
&#xD;
         14. pregnant women or patients with intention to become pregnant;&#xD;
&#xD;
         15. Participated in other clinical trials in the past 1 month;&#xD;
&#xD;
         16. Patients would not take drug continuously which could affect the evaluation of&#xD;
             efficacy;&#xD;
&#xD;
         17. Investigator evaluates as unsuitable to participate in this clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhong Wang, Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>China Academy of Chinese Science</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhong Wang, Ph.D</last_name>
    <phone>8610-64093207</phone>
    <email>zhonw@sina.vip.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Qiong Liu, Master</last_name>
    <phone>18612808665</phone>
    <email>694430355@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Yuquan Hospital of Tsinghua University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xingzhong Feng, Ph.D</last_name>
      <email>Fengxz9797@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>March 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>November 14, 2022</last_update_submitted>
  <last_update_submitted_qc>November 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>China Academy of Chinese Medical Sciences</investigator_affiliation>
    <investigator_full_name>Zhong Wang</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    <mesh_term>Diabetic Neuropathies</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/NCT04457531
org study id: LIUWEI-V1.1
nct id: NCT04457531
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Based on network pharmacology, Liuweiluobi Granule was screened to treat diabetes peripheral
      neuropathy with deficiency of the spleen and kidney and stasis-heat syndrome.In the
      preliminary animal experiment, it suggested that this granule had a significant protective
      effect on the peripheral motor nerves of diabetic peripheral neuropathy and the effect of
      anti-inflammation, and the prescription did not induce the death of zebrafish at a
      concentration of 1000 ug/mL, without any obvious toxicity. This study aims to evaluate the
      efficacy of Liuweiluobi Granule in improving neurotransmission function in patients with
      diabetic peripheral neuropathy through a pilot, randomized controlled study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean maximal nerve conduction velocity
time frame: 12 weeks
description: Mean maximal conduction velocity of the common peroneal motor nerve (MCV) and sensory nerve (SCV)
measure: Michigan Diabetic Peripheral Neuropathy Score (MDNS)
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Michigan Diabetic Peripheral Neuropathy Score (MDNS) is a 46 point clinical score, with score ranging from 0 to 3 (score of 0, normal; 1, mild to moderate; 2, severe and score of 3, absent). The score is more high means a worse outcome.In MDNS vibration, pain, and light touch are assessed with a 128 Hz tuning fork, a pin, and a 10g filament, respectively. The outcome measures were performed by the investigator at baseline and at the eighth week.
measure: Toronto clinical scoring system (TCSS)
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Toronto clinical scoring system (TCSS) includes three parts: the symptom score of the symptom, the reflection score of the nerve and the evaluation score of the sensory function test. Symptoms include numbness, pain, and needle-like sensation in the lower extremities Feelings of weakness, weakness, instability in walking, and similar symptoms of the upper limbs, such as normal score of 0, 1 point for the presence of corresponding symptoms, a total of 6 points; nerve reflex including ankle reflex and knee reflex, bilateral score, normal score of 0, weakened 1 point, 2 points for disappearance, 8 points in total; sensory function test includes 5 items of pain, temperature, pressure, vibration, and position on the right big toe, 0 points for normal, 1 point for abnormality, 5 points in total With a total score of 19 points. With a score of 0 to 5 do not exist in the DPN, 6 to 8 are mild DPN, 9 to 11 are moderate DPN, 12 to 19 are severe DPN.
measure: Quantitative symptoms scales of DPN in Traditional Chinese medicine
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
measure: HbA1c
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
measure: Changes in the level of aldose reductase
time frame: to 12 weeks
measure: Fasting blood glucose
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
measure: 2 hrs postprandial blood glucose
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
measure: Total lipids (TC)
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Lipid level
measure: triglycerides (TG)
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Lipid level
measure: high density lipoprotein cholesterol (HDL-C)
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Lipid level
measure: low density lipid Protein cholesterol (LDL-C).
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Lipid level
measure: Amino acids, lipid metabolites, vitamins, neurotransmitters and other metabolites
time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
description: Amino acids, lipid metabolites, vitamins, neurotransmitters and other metabolites will be analyzed and tested using targeted metabolic analysis.
arm group label: LiuWeiLuoBi Group
arm group type: Experimental
description: Patients will receive the treatment of LiuWeiLuoBi Granule for 12 weeks,twice a day added to the standard medical treatment.
arm group label: Control Group
arm group type: Other
description: Patients will receive the standard medical treatment for 12 weeks.
intervention type: Drug
intervention name: LiuWeiLuoBi Granule
description: LiuWeiLuoBi Granule is a Chinese medicine made from 6 herbal medicine, including Shaji(Sea-buckthorn), Honghua (Safflower), Jinyinhua(Honeysuckle),etc.
arm group label: LiuWeiLuoBi Group
intervention type: Other
intervention name: Standard medical treatment
description: Standard medical therapy is adhered to the guidline issued by American Diabetes Association and Chinese Diabetes Society at 2017, including keeping an appropriate diet, doing some exercises, the pharmacological therapy to control the blood glucose, blood pressure and blood lipids.
arm group label: Control Group
arm group label: LiuWeiLuoBi Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhong Wang, Ph.D
role: Study Chair
affiliation: China Academy of Chinese Science
last name: Zhong Wang, Ph.D
phone: 8610-64093207
email: zhonw@sina.vip.com
last name: Qiong Liu, Master
phone: 18612808665
email: 694430355@qq.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: China Academy of Chinese Medical Sciences
investigator full name: Zhong Wang
investigator title: Professor
mesh term: Peripheral Nervous System Diseases
mesh term: Diabetic Neuropathies