Clinical Evaluation on the Therapeutic Effect of Acupuncture Treatment for Alzheimer's Disease

Clinical Evaluation on the Therapeutic Effect of Acupuncture Treatment for Alzheimer's Disease: Multicenter Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Alzheimer Disease
• Intervention / Treatment: Other: Acupuncture; Drug: Donepezil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jian Pei, Doctor; Phone Number: 3534 00862164385700; Email: jianpei99@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital Fudan University
      • Contact: Houguang Zhou, Doctor
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Longhua Hospital Shanghai University of Traditional Chinese Medicine
      • Contact: Jian Pei, Doctor; Phone Number: 3534 00862164385700; Email: jianpei99@hotmail.com
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Shanghai Mental Center, Shanghai Jiaotong University of Medicial School
      • Contact: Tao Wang, Doctor; Phone Number: 00862163846590

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• aged between 50-85 years
• the diagnostic criteria of Neurological Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA)
• cognitive impairment based on the scores of the Chinese version of the Mini Mental State Examination (MMSE) (patients with mild to moderate Alzheimers disease, 11≤primary school degree≤22, 11≤junior high school degree or above≤26
• magnetic resonance imaging (MRI) confirmation of atrophy of the hippocampus or the medial temporal lobe volume, MRI manifestation of high possibility of Alzheimer Disease
• the Medial Temporal Lobe Atrophy Rating Scale (MTA-scale) score (≥2 for those under 75 years, and ≥3 for those over 75 years)
• voluntarily joining this study with informed consents

Exclusion Criteria:

• cognitive impairment caused by other factors (e.g. vascular dementia, dementia with Lewy bodies, frontotemporal dementia, hormone or metabolic abnormalities, hypothyroidism, folic acid or vitamin B12 deficiency, delirium or other mental and emotional disorders (such as schizophrenia and depression))
• a serious heart condition, hepatic disease, renal system disease, hematopoietic system disease, or whole-body malnutrition
• aphasia, disturbance of consciousness, or failure to cooperate with the related examinations due to physical disability
• anticoagulant treatments such as warfarin or heparin
• use of pacemakers or receiving acupuncture in the past 2 weeks

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acupuncture Treatment Group; Participants in this group will be given acupuncture treatment in combination with donepezil for 12 weeks.	Other: Acupuncture; 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.; Drug: Donepezil; 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.; Other Names: Donepezil Hydrochloride Tablets
Active Comparator: Donepezil Group; Participants in this group will be given only donepezil for 12 weeks.	Drug: Donepezil; 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.; Other Names: Donepezil Hydrochloride Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-cognition(ADAS-cog)	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.	Baseline(week -2), treatment at week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Mental State Examination(MMSE)	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.	Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.
Alzheimer's Disease Cooperative Study-Activity of Daily Living(ADCS-ADL)	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.	Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.
Quality of Life-Alzheimer's Disease(QOL-AD)	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.	Baseline(week -2), Treatment at week 12, Follow-up at weeks 12 and 24.
fractional amplitude of low frequency fluctuation (fALFF)	fALFF aquired by fMRI technique measures the relative contribution of low frequency fluctuations within a specific frequency band to the whole detectable frequency range	Baseline(week -2), Treatment at week 12
functional connectivity (FC)	FC aquired by fMRI technique measures the functional connectivity of specific brain regions to the whole brain	Baseline(week -2), Treatment at week 12

Collaborators and Investigators

• Sponsor: Shanghai University of Traditional Chinese Medicine
• Collaborators: Huashan Hospital; Shanghai Mental Health Center
• Investigators: Study Chair: Jian Pei, Doctor, Shanghai University of Traditional Chinese Medicine; Study Director: Houguang Zhou, Doctor, Huashan Hospital; Study Director: Tao Wang, Doctor, Mental Health Center Shanghai Jiao Tong University School of Medicine

Publications and helpful links

General Publications

• Fu QH, Pei J, Zhou HG, Wang T, Zhan YJ, Tao L, Xu J, Zhou Q, Wang LY. Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer's disease: a study protocol for a multicenter randomized controlled trial. Trials. 2022 Aug 19;23(1):695. doi: 10.1186/s13063-022-06532-1.
• Zhan Y, Fu Q, Pei J, Fan M, Yu Q, Guo M, Zhou H, Wang T, Wang L, Chen Y. Modulation of Brain Activity and Functional Connectivity by Acupuncture Combined With Donepezil on Mild-to-Moderate Alzheimer's Disease: A Neuroimaging Pilot Study. Front Neurol. 2022 Jul 11;13:912923. doi: 10.3389/fneur.2022.912923. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Acupuncture Treatment
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 18401970500

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No