Clinical Evaluation of Acupuncture Treatment on Alzheimer's Disease in APOE e4 Carriers and Non-Carriers

Clinical Evaluation of Acupuncture Treatment on Alzheimer's Disease in APOE e4 Carriers and Non-Carriers: A Randomized Controlled Trial

The goal of this clinical trial is to learn if acupuncture works to treat mild-to-moderate Alzheimer's disease, as well as the difference of its effect in APOE e4 carriers and non-carriers. It will also learn about the safety of acupuncture.

Researchers will compare acupuncture to a placebo (sham acupuncture) to see if acupuncture works to relieve the cognitive impairment and improve the ability of daily living and the quality of life. In addition, the plasma and neuroimaging biomarkers will be included as objective indexes.

Participants will:

Experience acupuncture or sham acupuncture 3 times per week for 12 weeks, and receive a 52-week follow-up.

Visit the clinic at Week 12, Week 38 and Week 64 for checkups and tests.

Study Overview

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

Detailed Description

This is a two-centre randomized controlled trial. A total of 176 participants with mild-to-moderate Alzheimer's disease, 88 APOE e4 carriers and 88 non-carriers, will be randomly assigned to either an acupuncture combined with donepezil group or a sham acupuncture combined with donepezil group with a ratio of 1:1. The main acupoints are DU 24, EX-HN 3, DU 20, EX-HN 1, GB 12, HT 7, KI 6, GB39. There will be 12 weeks of 3-session treatment for each participant, and a 52-week follow-up in total. The primary outcome is the change and effective rate from baseline in the ADAS-cog score measured at Week 12.

• Study Type: Interventional
• Enrollment (Estimated): 176
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yijun Zhan; Phone Number: +8618917699167; Email: jenniferzhan_lhzj@163.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Longhua Hospital, Shanghai University of Traditional Chinese Medicine
    • Contact: Yijun Zhan; Phone Number: +8618917699167; Email: jenniferzhan_lhzj@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged between 50-85 years
• Diagnosed by the 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
• Contraindications to undergoing an MRI scan such as claustrophobia or pacemaker implantation.
• 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: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acupuncture Treatment; Participants in this group will receive 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. There will be 12 weeks of 3-session treatment for each participant in total.; Drug: Donepezil; Donepezil 5 mg will be given once daily before bed-time for 12 weeks.
Active Comparator: Sham Acupuncture Treatment; Participants in this group will receive sham acupuncture treatment in combination with donepezil for 12 weeks.	Drug: Donepezil; Donepezil 5 mg will be given once daily before bed-time for 12 weeks.; Other: Sham Acupuncture; The Streitberger placebo needle will be used to simulate an acupuncture procedure without penetrating the skin. 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. There will be 12 weeks of 3-session treatment for each participant in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-cognition (ADAS-cog)	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.	Change from baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-cognition (ADAS-cog)	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.	Change from baseline to Week 38 (Follow-up 1) and Week 64 (Follow-up 2)
Alzheimer's Disease Cooperative Study-Activity of Daily Living (ADCS-ADL)	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.	Change from baseline to Week 12, Week 38 (Follow-up 1) and Week 64 (Follow-up 2)
Quality of Life-Alzheimer's Disease(QOL-AD)	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.	Change from baseline to Week 12, Week 38 (Follow-up 1) and Week 64 (Follow-up 2)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphorylated tau at threonine 181 (p-tau181)	Plasma p-tau181measured by Single Molecule Array (Simoa) as the plasma biomarker.	Change from baseline to Week 12 and Week 64 (Follow-up 2)
Cerebral Blood Flow (CBF)	CBF acquired by arterial spin labeling (ASL) magnetic resonance imaging (MRI) technique measures the blood flow condition of the whole brain.	Change from baseline to Week 12 and Week 64 (Follow-up 2)

Collaborators and Investigators

• Sponsor: ZhanYJ
• Collaborators: Shanghai Minimally Invasive Surgery Center
• Investigators: Study Chair: Yijun Zhan, Shanghai University of Traditional Chinese Medicine; Study Director: Houguang Zhou, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: May 12, 2024
• First Submitted That Met QC Criteria: May 12, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 18, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neurotransmitter Agents; Cholinergic Agents; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 23Y11921000

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No