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Progress of Mild Alzheimer's Disease in Participants on Acupuncture Versus Sham Acupuncture

Not Applicable
Recruiting
Conditions
Alzheimer Disease 1
Interventions
Device: Active acupuncture
Device: Sham acupuncture
Registration Number
NCT05078944
Lead Sponsor
Shanghai Institute of Acupuncture, Moxibustion and Meridian
Brief Summary

To determine if adjunctive acupuncture acts as an AD treatment rather than a placebo, and identify if benefits are linked to shifts of the gut microbiota.

Detailed Description

Acupuncture is used as an adjuvant therapy for Alzheimer's disease (AD), but available evidence for efficacy is weak. Growing studies suggest that resident gut microbiota contributes to the development and progression of AD. Acupuncture is reported to treat gastrointestinal and neurodegenerative disorders via the gut-brain axis. The aim is to determine if adjunctive acupuncture acts as an AD treatment rather than a placebo, and identify if benefits are linked to shifts of the gut microbiota.

This is a randomized, participant-masked, sham-controlled trial. One hundred and sixty participants with mild AD will be randomly assigned (1:1) to either active acupuncture or non-penetrating sham acupuncture (3 times weekly for 14 weeks) added to donepezil treatment (5 mg per day for 28 weeks). The primary efficacy outcome is the change from baseline to week 28 in the Alzheimer's disease Assessment Scale (ADAS-cog12). Secondary efficacy outcomes include other assessments of the Mini-Mental State Examination (MMSE), the Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI) and gut microbiota.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
240
Inclusion Criteria
  • Meets the diagnostic criteria for probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA)
  • Scored 1.0 by the Clinical Dementia Rating Scale (CDR) Global Score
Exclusion Criteria
  • Dementia due to other causes
  • Evidence of a clinically relevant or unstable psychiatric disorder
  • Has irritable bowel syndrome or inflammatory bowel disease
  • Has unstable or severe cardiovascular, hepatic, renal, respiratory, endocrinologic, neurologic diseases and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study
  • Has visual or hearing disorder, defeating completion of evaluation
  • Use of AD therapy (except for donepezil hydrochloride) which cannot be stopped
  • Use of antibiotics within 1 month prior to enrollment
  • Has a history of gastrointestinal surgery (except for appendicitis and hernia surgery)
  • Without a reliable caregiver who will accompany the participant during treatment and assessment, and monitor administration of the prescribed medications
  • With cardiac pacemaker or metal allergy
  • Once experienced electroacupuncture treatment before at any time (manual acupuncture is allowed)
  • Premenopausal woman

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active acupuncture + DonepezilActive acupunctureActive acupuncture treatment is to be taken 3 sessions weekly over a period of 14 weeks. Donepezil hydrochloride (5 mg/capsule, Weicai Pharmaceutical Co., Ltd, China) is to be taken 5 mg daily over 32 weeks (including 4-week run-in) Intervention: Device: Acupuncture + Drug: Donepezil hydrochloride
Sham acupuncture + DonepezilSham acupunctureSham acupuncture treatment with no skin penetration and no current output on sham acupoints is to be taken 3 sessions weekly over a period of 14 weeks. Donepezil hydrochloride (5 mg/capsule, Weicai Pharmaceutical Co., Ltd, China) is to be taken 5 mg daily over 32 weeks (including 4-week run-in) Intervention: Device: Sham acupuncture + Drug: Donepezil hydrochloride
Sham acupuncture + DonepezilDonepezil HydrochlorideSham acupuncture treatment with no skin penetration and no current output on sham acupoints is to be taken 3 sessions weekly over a period of 14 weeks. Donepezil hydrochloride (5 mg/capsule, Weicai Pharmaceutical Co., Ltd, China) is to be taken 5 mg daily over 32 weeks (including 4-week run-in) Intervention: Device: Sham acupuncture + Drug: Donepezil hydrochloride
Active acupuncture + DonepezilDonepezil HydrochlorideActive acupuncture treatment is to be taken 3 sessions weekly over a period of 14 weeks. Donepezil hydrochloride (5 mg/capsule, Weicai Pharmaceutical Co., Ltd, China) is to be taken 5 mg daily over 32 weeks (including 4-week run-in) Intervention: Device: Acupuncture + Drug: Donepezil hydrochloride
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 12 Item Subscore (ADAS-Cog12)Baseline, Week 7, Week 14, Week 21, Week 28

The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS consists of 12 items (ranges from 0 to 75). Higher scores indicating greater cognitive impairment.

Secondary Outcome Measures
NameTimeMethod
Incidence of adverse eventsWeek -4 to Week 28

Including subcutaneous hematoma, local errhysis at acupoints, sharp pain, palpitation, nausea, dizziness and faint during acupuncture.

Change in gut microbiota diversity based on 16S rRNA gene sequencing analysisBaseline, Week 14, Week 28

Stool samples will be processed to extract DNA, followed by 16S rRNA gene sequencing analysis using QIIME and R packages (v3.2.0).

Change From Baseline in Neuropsychiatric Inventory (NPI)Baseline, Week 7, Week 14, Week 21, Week 28

NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. Total score ranges from 0 to 144, with lower scores indicating fewer behavioral disturbances

Change From Baseline in Mini-Mental State Examination (MMSE)Baseline, Week 7, Week 14, Week 21, Week 28

MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges from 0 to 30; lower score indicates greater disease severity.

Treatment credibilityWeek 1, Week 14

The treatment credibility scale will be assessed by asking participants to rate their response to four questions on a 5-point scale developed by Borkovec and Nau. Total score ranges from 0 to 20; higher score indicates greater treatment credibility.

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)Baseline, Week 7, Week 14, Week 21, Week 28

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity.

Trial Locations

Locations (1)

Shanghai Institute of Acupuncture, Moxibustion and Meridian Organization

🇨🇳

Shanghai, China

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