<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/NCT03810794</url>
  </required_header>
  <id_info>
    <org_study_id>18401970500</org_study_id>
    <nct_id>NCT03810794</nct_id>
  </id_info>
  <brief_title>Clinical Evaluation on the Therapeutic Effect of Acupuncture Treatment for Alzheimer's Disease</brief_title>
  <official_title>Clinical Evaluation on the Therapeutic Effect of Acupuncture Treatment for Alzheimer's Disease: Multicenter Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai University of Traditional Chinese Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Huashan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai University of Traditional Chinese Medicine</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this proposed study is to evaluate the effect and safety of acupuncture&#xD;
      combined therapy on cognitive function, daily living ability and quality of life of&#xD;
      Alzheimer's disease by using the international dementia certification scale. In this 12-week,&#xD;
      assessor-blind, a Multi-center randomized, controlled study of acupuncture as additional&#xD;
      treatment with Donepezil, a total of 180 patients with Alzheimer's disease will be recruited.&#xD;
      The patients will be randomly assigned to acupuncture combined with Donepezil (n =90) or&#xD;
      Donepezil treatment (n =90). (36 sessions, 3 sessions a week). Changes in the cognition over&#xD;
      time measured using ADAS-cog is the primary outcome. MMSE, ADCS-ADL and QOL-AD are the&#xD;
      secondary outcomes. The study will be conducted at LongHua Hospital Shanghai University of&#xD;
      Traditional Chinese Medicine, Huashan Hospital Fudan University, and Mental Health Center&#xD;
      Shanghai Jiao Tong University School of Medicine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: To evaluate the effect and safety of acupuncture combined therapy on cognitive&#xD;
      function, daily living ability and quality of life of Alzheimer's disease by using the&#xD;
      international dementia certification scale.&#xD;
&#xD;
      Methods/design: A total of 180 participants with mild to moderate Alzheimer's disease will be&#xD;
      randomly assigned to either an acupuncture combined with donepezil group or a donepezil group&#xD;
      with a ratio of 1:1. Participants in the acupuncture combined with donepezil group will&#xD;
      receive acupuncture treatment in combination with donepezil for 12 weeks and at same time&#xD;
      taking donepezil. The main acupoints are DU 24, EX-HN 3, DU 20, EX-HN 1, GB 12, HT 7, KI 6,&#xD;
      GB39, and then selecting other acupoints according to TCM syndrome. The electric stimulator&#xD;
      will be applied to DU 24, GB 12, HT 7, and LR 3 or SP 6 with a disperse-dense wave of 2/50&#xD;
      Hz, 0.5-1.0 mA. There are 3 sessions per week with each session lasting for 30 min. There&#xD;
      will be 12 weeks of treatment for each participant in total. Donepezil 5 mg will be given&#xD;
      once daily before bed-time for 12 weeks. After the clinical trial, participants will be given&#xD;
      conventional treatment clinically. Participants in the control group will take donepezil&#xD;
      only. A follow-up will be conducted 24 weeks after the treatment. The primary outcome is the&#xD;
      change and effective rate from baseline in the ADAS-cog score measured at week 12. The&#xD;
      secondary outcomes contains The change from baseline in MMSE score, ADCS-ADL score, QOL-AD&#xD;
      score measured at weeks 12, 24 and 36.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2022</primary_completion_date>
  <phase>N/A</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Alzheimer's Disease Assessment Scale-cognition(ADAS-cog)</measure>
    <time_frame>Baseline(week -2), treatment at week 12</time_frame>
    <description>The primary outcome are the change and effective rate from baseline in the Alzheimer's Disease Assessment Scale-cognition(ADAS-cog) score measured at week 12. The maximum score of the ADAS-cog is 70 including 12 items. The questions in this scale contain word recall task, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition task, remembering test directions, spoken language, word-finding difficulty, comprehension and attention. In general, a normal score for someone who does not have AD or another type of dementia is 5. The higher scores indicate higher degree of cognitive dysfunction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Minimum Mental State Examination(MMSE)</measure>
    <time_frame>Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.</time_frame>
    <description>The change from baseline in total Minimum Mental State Examination(MMSE) score should be measured at weeks 12, 24 and 36. The maximum score of the MMSE is 30. The questions in this scale include orientation to time, orientation to place, attention and calculation, recall of three words, and visual construction. The lower scores indicate higher degree of cognitive dysfunction. The score is related to degree of education. In general, the score of normal people is 27-30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alzheimer's Disease Cooperative Study-Activity of Daily Living(ADCS-ADL)</measure>
    <time_frame>Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.</time_frame>
    <description>The change from baseline in the Alzheimer's Disease Cooperative Study-Activity of Daily Living(ADCS-ADL) score should be measured at weeks 12, 24 and 36. The maximum of the ADCS-ADL score is 54 containing 19 domains about assessment of basic and operational ability of daily living. The higher scores indicate higher ability of daily living.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life-Alzheimer's Disease(QOL-AD)</measure>
    <time_frame>Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.</time_frame>
    <description>The change from baseline in the Quality of Life-Alzheimer's Disease(QOL-AD) score should be measured at weeks 12, 24 and 36. The QOL-AD score includes 13 items about physical health, mental health, social and financial assessment, and quality of life. The total score ranges from 13 to 52. The higher scores indicate higher quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fractional amplitude of low frequency fluctuation (fALFF)</measure>
    <time_frame>Baseline(week -2), Treatment at week 12</time_frame>
    <description>fALFF aquired by fMRI technique measures the relative contribution of low frequency fluctuations within a speciﬁc frequency band to the whole detectable frequency range</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>functional connectivity (FC)</measure>
    <time_frame>Baseline(week -2), Treatment at week 12</time_frame>
    <description>FC aquired by fMRI technique measures the functional connectivity of specific brain regions to the whole brain</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Alzheimer Disease</condition>
  <condition>Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Acupuncture Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will be given acupuncture treatment in combination with donepezil for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Donepezil Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this group will be given only donepezil for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Acupuncture</intervention_name>
    <description>The main acupoints are DU 24, EX-HN 3, DU 20, EX-HN 1, GB 12, HT 7, KI 6, GB39, and then selecting other acupoints according to TCM syndrome. The electric stimulator will be applied to DU 24, GB 12, HT 7, and LR 3 or SP 6 with a disperse-dense wave of 2/50 Hz, 0.5-1.0 mA. There are three sessions per week with each session lasting for 30 min. There will be 12 weeks of treatment for each participant in total.</description>
    <arm_group_label>Acupuncture Treatment Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donepezil</intervention_name>
    <description>Donepezil 5 mg will be given once daily before bed-time for 12 weeks. After the clinical trial, participants will be given conventional treatment clinically.</description>
    <arm_group_label>Acupuncture Treatment Group</arm_group_label>
    <arm_group_label>Donepezil Group</arm_group_label>
    <other_name>Donepezil Hydrochloride Tablets</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged between 50-85 years&#xD;
&#xD;
          -  the diagnostic criteria of Neurological Communicative Disorders and Stroke and the&#xD;
             Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA)&#xD;
&#xD;
          -  cognitive impairment based on the scores of the Chinese version of the Mini Mental&#xD;
             State Examination (MMSE) (patients with mild to moderate Alzheimers disease,&#xD;
             11≤primary school degree≤22, 11≤junior high school degree or above≤26&#xD;
&#xD;
          -  magnetic resonance imaging (MRI) confirmation of atrophy of the hippocampus or the&#xD;
             medial temporal lobe volume, MRI manifestation of high possibility of Alzheimer&#xD;
             Disease&#xD;
&#xD;
          -  the Medial Temporal Lobe Atrophy Rating Scale (MTA-scale) score (≥2 for those under 75&#xD;
             years, and ≥3 for those over 75 years)&#xD;
&#xD;
          -  voluntarily joining this study with informed consents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cognitive impairment caused by other factors (e.g. vascular dementia, dementia with&#xD;
             Lewy bodies, frontotemporal dementia, hormone or metabolic abnormalities,&#xD;
             hypothyroidism, folic acid or vitamin B12 deficiency, delirium or other mental and&#xD;
             emotional disorders (such as schizophrenia and depression))&#xD;
&#xD;
          -  a serious heart condition, hepatic disease, renal system disease, hematopoietic system&#xD;
             disease, or whole-body malnutrition&#xD;
&#xD;
          -  aphasia, disturbance of consciousness, or failure to cooperate with the related&#xD;
             examinations due to physical disability&#xD;
&#xD;
          -  anticoagulant treatments such as warfarin or heparin&#xD;
&#xD;
          -  use of pacemakers or receiving acupuncture in the past 2 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jian Pei, Doctor</last_name>
    <role>Study Chair</role>
    <affiliation>Shanghai University of Traditional Chinese Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Houguang Zhou, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tao Wang, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Mental Health Center Shanghai Jiao Tong University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jian Pei, Doctor</last_name>
    <phone>00862164385700</phone>
    <phone_ext>3534</phone_ext>
    <email>jianpei99@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>LongHua Hospital Shanghai University of Traditional Chinese Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jian Pei, Doctor</last_name>
      <phone>00862164385700</phone>
      <phone_ext>3534</phone_ext>
      <email>jianpei99@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shanghai Mental Center, Shanghai Jiaotong University of Medicial School</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tao Wang, Doctor</last_name>
      <phone>00862163846590</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Huashan Hospital Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Houguang Zhou, Doctor</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>July 23, 2022</last_update_submitted>
  <last_update_submitted_qc>July 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acupuncture Treatment</keyword>
  <keyword>Alzheimer's Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Donepezil</mesh_term>
  </intervention_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/NCT03810794
org study id: 18401970500
nct id: NCT03810794
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The objective of this proposed study is to evaluate the effect and safety of acupuncture
      combined therapy on cognitive function, daily living ability and quality of life of
      Alzheimer's disease by using the international dementia certification scale. In this 12-week,
      assessor-blind, a Multi-center randomized, controlled study of acupuncture as additional
      treatment with Donepezil, a total of 180 patients with Alzheimer's disease will be recruited.
      The patients will be randomly assigned to acupuncture combined with Donepezil (n =90) or
      Donepezil treatment (n =90). (36 sessions, 3 sessions a week). Changes in the cognition over
      time measured using ADAS-cog is the primary outcome. MMSE, ADCS-ADL and QOL-AD are the
      secondary outcomes. The study will be conducted at LongHua Hospital Shanghai University of
      Traditional Chinese Medicine, Huashan Hospital Fudan University, and Mental Health Center
      Shanghai Jiao Tong University School of Medicine.
Objective: To evaluate the effect and safety of acupuncture combined therapy on cognitive
      function, daily living ability and quality of life of Alzheimer's disease by using the
      international dementia certification scale.

      Methods/design: A total of 180 participants with mild to moderate Alzheimer's disease will be
      randomly assigned to either an acupuncture combined with donepezil group or a donepezil group
      with a ratio of 1:1. Participants in the acupuncture combined with donepezil group will
      receive acupuncture treatment in combination with donepezil for 12 weeks and at same time
      taking donepezil. The main acupoints are DU 24, EX-HN 3, DU 20, EX-HN 1, GB 12, HT 7, KI 6,
      GB39, and then selecting other acupoints according to TCM syndrome. The electric stimulator
      will be applied to DU 24, GB 12, HT 7, and LR 3 or SP 6 with a disperse-dense wave of 2/50
      Hz, 0.5-1.0 mA. There are 3 sessions per week with each session lasting for 30 min. There
      will be 12 weeks of treatment for each participant in total. Donepezil 5 mg will be given
      once daily before bed-time for 12 weeks. After the clinical trial, participants will be given
      conventional treatment clinically. Participants in the control group will take donepezil
      only. A follow-up will be conducted 24 weeks after the treatment. The primary outcome is the
      change and effective rate from baseline in the ADAS-cog score measured at week 12. The
      secondary outcomes contains The change from baseline in MMSE score, ADCS-ADL score, QOL-AD
      score measured at weeks 12, 24 and 36.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Alzheimer's Disease Assessment Scale-cognition(ADAS-cog)
time frame: Baseline(week -2), treatment at week 12
description: The primary outcome are the change and effective rate from baseline in the Alzheimer's Disease Assessment Scale-cognition(ADAS-cog) score measured at week 12. The maximum score of the ADAS-cog is 70 including 12 items. The questions in this scale contain word recall task, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition task, remembering test directions, spoken language, word-finding difficulty, comprehension and attention. In general, a normal score for someone who does not have AD or another type of dementia is 5. The higher scores indicate higher degree of cognitive dysfunction.
measure: Minimum Mental State Examination(MMSE)
time frame: Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.
description: The change from baseline in total Minimum Mental State Examination(MMSE) score should be measured at weeks 12, 24 and 36. The maximum score of the MMSE is 30. The questions in this scale include orientation to time, orientation to place, attention and calculation, recall of three words, and visual construction. The lower scores indicate higher degree of cognitive dysfunction. The score is related to degree of education. In general, the score of normal people is 27-30.
measure: Alzheimer's Disease Cooperative Study-Activity of Daily Living(ADCS-ADL)
time frame: Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.
description: The change from baseline in the Alzheimer's Disease Cooperative Study-Activity of Daily Living(ADCS-ADL) score should be measured at weeks 12, 24 and 36. The maximum of the ADCS-ADL score is 54 containing 19 domains about assessment of basic and operational ability of daily living. The higher scores indicate higher ability of daily living.
measure: Quality of Life-Alzheimer's Disease(QOL-AD)
time frame: Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.
description: The change from baseline in the Quality of Life-Alzheimer's Disease(QOL-AD) score should be measured at weeks 12, 24 and 36. The QOL-AD score includes 13 items about physical health, mental health, social and financial assessment, and quality of life. The total score ranges from 13 to 52. The higher scores indicate higher quality of life.
measure: fractional amplitude of low frequency fluctuation (fALFF)
time frame: Baseline(week -2), Treatment at week 12
description: fALFF aquired by fMRI technique measures the relative contribution of low frequency fluctuations within a speciﬁc frequency band to the whole detectable frequency range
measure: functional connectivity (FC)
time frame: Baseline(week -2), Treatment at week 12
description: FC aquired by fMRI technique measures the functional connectivity of specific brain regions to the whole brain
arm group label: Acupuncture Treatment Group
arm group type: Experimental
description: Participants in this group will be given acupuncture treatment in combination with donepezil for 12 weeks.
arm group label: Donepezil Group
arm group type: Active Comparator
description: Participants in this group will be given only donepezil for 12 weeks.
intervention type: Other
intervention name: Acupuncture
description: The main acupoints are DU 24, EX-HN 3, DU 20, EX-HN 1, GB 12, HT 7, KI 6, GB39, and then selecting other acupoints according to TCM syndrome. The electric stimulator will be applied to DU 24, GB 12, HT 7, and LR 3 or SP 6 with a disperse-dense wave of 2/50 Hz, 0.5-1.0 mA. There are three sessions per week with each session lasting for 30 min. There will be 12 weeks of treatment for each participant in total.
arm group label: Acupuncture Treatment Group
intervention type: Drug
intervention name: Donepezil
description: Donepezil 5 mg will be given once daily before bed-time for 12 weeks. After the clinical trial, participants will be given conventional treatment clinically.
arm group label: Acupuncture Treatment Group
arm group label: Donepezil Group
other name: Donepezil Hydrochloride Tablets
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jian Pei, Doctor
role: Study Chair
affiliation: Shanghai University of Traditional Chinese Medicine
last name: Houguang Zhou, Doctor
role: Study Director
affiliation: Huashan Hospital
last name: Tao Wang, Doctor
role: Study Director
affiliation: Mental Health Center Shanghai Jiao Tong University School of Medicine
last name: Jian Pei, Doctor
phone: 00862164385700
phone ext: 3534
email: jianpei99@hotmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Donepezil