The Effect of Acupuncture Treatment on Cognitive Functions and Brain Networks for Long COVID

Official title

The Effect of Acupuncture Treatment on Cognitive Functions and Brain Networks for Long COVID: a Multimodal Magnetic Resonance Imaging Study

Overview

Background of study: Long COVID(LC) is a prevalent sequalae of SARS-CoV-2 infection and can affect multiple organ systems. Cognitive dysfunction is one of the most common symptoms in LC with 22% prevalence. It can persist for years and significantly reduce patients' quality of life. Brain network is the neural basis underlying human cognitive processes. Diffusion tensor imaging (DTI) and functional magnetic resonance imaging(fMRI) research has revealed that alterations of network characteristics were associated with cognitive impairments across attention, memory, executive function and language in LC. Currently, there is no accepted therapy for cognitive impairment in LC. Acupuncture, as a Traditional Chinese Medicine therapy, has potential to improve cognitive deficits for LC. However, research focusing on the impact of acupuncture on cognitive functions in LC is rare. Additionally, no one has evaluated the mechanism of acupuncture improving cognitive functions in LC. Objective of the study: This study aims to assess the effect of acupuncture treatment on cognitive function and explore the central mechanism of acupuncture therapy in improving cognitive function for LC using cognitive assessments, DTI and resting-state fMRI. Study design: A prospective, three-armed, randomized controlled trial with DTI and rs-fMRI. Adults with LC will be randomly assigned to acupuncture, sham acupuncture, or waitlist control group in a 1:1:1 ratio, receiving 8-week intervention or waiting. Cognitive function and topological attributes of brain networks will be examined at baseline and 8th week. Study population: Patients fulfilling World Health Organization (WHO) criteria for LC will be included in this study.

Interventions

• Other Acupuncture
  Two sets of acupoints will be alternatively acupunctured. The first set of acupuncture points incudes Baihui (GV20), Shenting (GV24), bilateral Neiguan (PC6), Qihai (CV6), Guanyuan (CV4), bilateral Zusanli (ST36), bilateral Sanyinjiao (SP6). The second set of acupoints consist of Sishenchong (EX-HN1), bilateral Ganshu (BL18), bilateral Pishu (BL20), bilaetral Shenshu (BL23). The treatment consists of 24 sessions of 30 minutes, given within eight weeks (three sessions per week).A set of acupoints
• Other Sham acupuncture
  Nonpenetrating acupuncture on non-acupoints will be performed using Park sham acupuncture device (0.25 mm in diameter and 40 mm in length, Hwatuo, Suzhou, China) for participants. Two sets of non-acupoints will be alternatively acupunctured. The first set of sham acupoints includes bilateral non-acupoint 1, non-acupoint 2, non-acupoint 3, bilateral non-acupoint 4, bilateral non-acupoint 5. The second set consists of bilateral non-acupoint 6, bilateral non-acupoint 7, bilateral non-acupoint 8. Th

Primary outcome measures

• Change of Addenbrooke's Cognitive Examination-III total score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change of Phonemic Fluency Test score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]

Secondary outcome measures (12)

• Changes of Digit Span Test scores from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change of Symbol Digit Modality Test score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Changes of Trail Making Test scores from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Changes of Rey Auditory Verbal Learning Test scores from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Changes of Rey-Osterrieth Complex Figure Test scores from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Changes of Stroop Test scores from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change of Category Fluency Test Score from baseline to the end of 8 weeks. [Time frame: Baseline and 8 weeks]
• Change of Action Fluency Test Score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change of Boston Naming Test score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change in Fatigue Severity Scale score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change of the Generalized Anxiety Disorde-7 score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]
• Change of Hamilton Depression Scale score from baseline to the end of 8 weeks [Time frame: Baseline and 8 weeks]

Eligibility criteria

Inclusion criteria

• Age 18-60 years
• Fulfilling WHO criteria for long COVID
• History of confirmed COVID-19 through RT-PCR of nasopharyngeal swab or antigen test of nasal swab ;
• Having subjective cognitive problems
• Native Chinese speakers
• Right handedness
• Voluntary to participate in the study and signing the informed consent form.

Exclusion criteria

• Preexisting cognitive symptoms before COVID-19
• Previous or current diagnosis of chronic conditions that may affect cognitive performances (such as neurological, psychiatric disorders, organ failure, chronic infectious diseases)
• Prior loss of consciousness
• History of major surgery within a year
• Long-term use of drugs that may influence cognition(such as tranquilizer, antidepressant, immunosuppressor)
• Previous acupuncture treatment within 3 months
• Involvement of other clinical study within 4 weeks
• Obesity(BMI≥28)
• Sensory disorders(deafness, color blindness)
• Limb dysfunction
• Metal implantation
• Claustrophobia
• Pregnancy or lactation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Chengdu University of Traditional Chinese Medicine — Chengdu
• Chengdu University of Traditional Chinese Medicine — Chengdu

Publications

• Luo T, Luo Y, Liu D, Jin H, An Y, Huang J, Luo K, Guo Y, Wang D, Huang L, Wu X. Acupuncture for cognitive functions in post-COVID-19 condition: study protocol of a three-armed, randomized controlled trial with multimodal MRI. Front Med (Lausanne). 2026 Apr 29;13:1796351. doi: 10.3389/fmed.2026.1796351. eCollection 2026. PMID 42136829

Identifiers

NCT: NCT07355751 · 2025KL-086

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗