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NCT Number: NCT06758154

Efficacy and Olfactory Network of Electro-acupuncture for Subjective Cognitive Decline: A Multicenter Randomized Controlled Trial and fMRI Study

Subjective cognitive decline (SCD) is the early diagnosis and treatment window period of Alzheimer's disease (AD), and the identification of SCD individuals who will progress to AD (pSCD) is a research hotspot. Based on olfactory fMRI,previous studies have found that SCD individuals showed damaged entorhinal neural circuits. After follow-up, the incidence of pSCD increased by three times. But,the spatiotemporal characteristics of the entorhinal neural circuits and whether it has the value of individualized prediction and intervention target need to be further studied. Thus, based on multi-center ambispective cohort study at home and abroad, we will (1) build a new paradigm of synchronous fMRI-EEG olfactory task state Oddball experiment, jointly representational similarity analysis, extract spatiotemporal characteristics of neural circuits damage, and discover and verify that the entorhinal neural circuits are vulnerable brain regions; (2) establish the middle fusion model of vulnerable brain region combined with the methods of olfactory task-fMRI activation image generation, functional connectome gradient,etc.; Then, establish late fusion multi-omics multi-task model combined with the new methods of molecularomics such as ultra-deep total proteomics and metabonomics proposed by the research group to accurately identify pSCD; (3) carry out the precise intervention of image-guided "olfactory three-needle" acupuncture with the entorhinal neural circuits as the target. Through clinical RCT research and mouse model, the remodeling mechanism of vulnerable brain regions will be clarified.This project will provide the basis for early diagnosis and treatment of the AD risk population.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

55 year–79 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Meet the diagnostic criteria for SCD diseases;
  • 55-79 years old;
  • ≥8 years of schooling;
  • Right-handed;
  • Sign the informed consent.

Exclusion criteria

  • Have received other antidepressant therapy or involved in other clinical trials in the previous 2weeks.
  • Infarct located in the left DLPFC.
  • Positive psychiatric history and major trauma exposure history, such as depression, epilepsy, etc., in the past.
  • Other serious concomitant diseases (aphasia, severe edema, venous thrombosis, arteriosclerosis occlusion, diabetic vascular disease, peripheral neuropathy, spinal lesions, brain trauma, intracranial infection, brain tumors, etc.) or secondary diseases (heart, liver, renal failure, etc.).
  • Infection around acupoints and/or intolerance to acupuncture manipulation.
  • MRI or rTMS contraindications (claustrophobia, metal implants, cochlear implants, impulsator, etc.).

Treatment and study plan

"TXJN" electro-acupuncture

Device

Firstly, EA treatment will be administered at the Neiguan (PC6, bilateral), Shenting(GV23), Yingxiang(LI20, bilateral), Yintang(GV29) acupoints. Disposable stainless-steel needles (0.25 mm × 25 mm; Huatuo brand, Suzhou Medical Supplies Factory Co., LTD., Suzhou City, China) will be used. After skin disinfection, the acupuncturists will twist and thrust the needle handles to achieve the sensations of achiness, heaviness, and numbness (known as de qi) at all above-mentioned acupoints. Following needle manipulations, EA instruments (SDZ-V, Hwato brand, Suzhou Medical Supplies Factory Co., Ltd., Suzhou City, China) will be used to attach the needle handles at PC6, GV23, LI20, GV29, with a dilatational wave of 5 Hz and a current intensity of 2 ~ 4 mA depending on the patient's tolerance. The needles will be removed after 30 min. Participants will receive 24 sessions over 8 weeks at a frequency of 3 times per week.

Sham acupuncture

Device

Firstly, EA treatment will be administered at the non-acupoints near above-mentioned real acupoints. Disposable stainless-steel needles (0.25 mm × 25 mm; Huatuo brand, Suzhou Medical Supplies Factory Co., LTD., Suzhou City, China) will be used. After skin disinfection, the acupuncturists will take the needle into the acupoints without the sensations of de qi. Following needle manipulations, EA instruments (SDZ-V, Hwato brand, Suzhou Medical Supplies Factory Co., Ltd., Suzhou City, China) will be used to attach the needle handles at non-acupoints without the current. The needles will be removed after 30 min. Participants will receive 24 sessions over 8 weeks at a frequency of 3 times per week.

Primary outcomes

  1. Comprehensive Z score

    Time frame: Before and 8 weeks after treatment

    The neuropsychological scale of 8 objective cognitive assessments used in the study (including AVLT (S and L), AFT, BNT, TMT (A and B), SCWT-C, DSST, DST, CDT) was converted into Z scores for description. Specific operations: Standardize the score of a single cognitive domain scale, create the corresponding Z-score data set, calculate the average value of each data in the group to generate a single Z-score, and sum the Z-score of each single cognitive domain to generate the overall Z-score. Patients were evaluated before treatment and 8 weeks later.

  2. Multimodal magnetic resonance imaging of olfactory related neural circuits

    Time frame: Before and 8 weeks after treatment

    Structural MRI(3DTIWI/3DT2WI/3Dflair), functional MRI(BOLD\\NODDI\\ASL\\ QSM)

Secondary outcomes

  1. mini-mental state examination, MMSE

    Time frame: Before and 8 weeks after treatment

  2. Montreal Cognitive Assessment,MoCA

    Time frame: Before and 8 weeks after treatment

  3. Subjective cognitive self-scoring

    Time frame: Before and 8 weeks after treatment

  4. Hamilton Depression Scale,HAMD

    Time frame: Before and 8 weeks after treatment

  5. the Geriatric Depression Scale,GDS

    Time frame: Before and 8 weeks after treatment

  6. Hamilton Anxiety Scale,HAMA

    Time frame: Before and 8 weeks after treatment

  7. auditory verbal learning test,AVLT

    Time frame: Before and 8 weeks after treatment

  8. Rey complex figure test,CFT

    Time frame: Before and 8 weeks after treatment

  9. Boston naming test,BNT

    Time frame: Before and 8 weeks after treatment

  10. Animal fluency test,AFT

    Time frame: Before and 8 weeks after treatment

  11. rail making test-A,TMT-A

    Time frame: Before and 8 weeks after treatment

  12. rail making test-B,TMT-B

    Time frame: Before and 8 weeks after treatment

  13. complex figure test, CFT

    Time frame: Before and 8 weeks after treatment

  14. clock drawing test,CDT

    Time frame: Before and 8 weeks after treatment

  15. Symbol Digit Modalities Test,SDMT

    Time frame: Before and 8 weeks after treatment

  16. odor threshold test,OTT

    Time frame: Before and 8 weeks after treatment

  17. The olfactory behavioral test

    Time frame: Before and 8 weeks after treatment

  18. Spatial navigation behavior test

    Time frame: Before and 8 weeks after treatment

  19. Pittsburgh sleep quality index,PSQI

    Time frame: Before and 8 weeks after treatment

  20. TCM physique classification scale

    Time frame: Before and 8 weeks after treatment

  21. TCM syndrome type scale of mild cognitive impairment

    Time frame: Before and 8 weeks after treatment

Other outcomes

  1. Acceptance survey

    Time frame: After 8 weeks of treatment

  2. Adverse event

    Time frame: During treatment

Sponsors and collaborators

Lead sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Other

Registry information

Important dates

Study start
2024
Primary completion
2026
Study completion
2028
First posted
Jan 3, 2025
Registry last updated
Jan 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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