Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment

Not Applicable

Recruiting

• Conditions: Perioperative Neurocognitive Disorder

• Registration Number: NCT06488807
• Lead Sponsor: Shanghai 10th People's Hospital

Brief Summary

Perioperative neurocognitive disorder (PND) is one of the most common postoperative complications among elderly patients. However, the mechanism and targeted intervention of PND remains unclear. Our previous clinical studies demonstrated the association between olfactory impairment and PND. Moreover, our translational studies showed that anesthesia/surgery induced olfactory impairment and caused cognitive impairment in mice and olfactory enrichment could prevent the anesthesia/surgery-induced cognitive impairment. However, there was no clinical investigation to determine whether olfactory enrichment can mitigate PND in elderly patients. Therefore, we propose determining whether olfactory enrichment can prevent and/or treat PND in elderly patients.

Detailed Description

The study will be a double-blinded, randomized controlled trial. Participants (65 years old or older) undergoing scheduled orthopaedic surgery (≥2 hours, under general anesthesia) will be randomized to either olfactory enrichment group or sham group. Participants in olfactory enrichment group will receive olfactory enrichment with a dispenser twice sessions per day on preoperative day 1-3 and postoperative day 1-3 (30 min per session, 4 odors for each session) while participants in sham group will be equipped with the same pattern except that water will be used in the dispenser. Participants will be assessed twice daily by a research assistant blinded to allocation. The primary outcome will be the incidence of postoperative delirium measured by the Confusion Assessment Method on postoperative days 1, 2 and 3. The secondary outcomes will be the severity of postoperative delirium, cognitive function, plasma Tau-PT217 level, and olfactory function.

Study Timeline

• Study First Submitted: 2024-06-15
• Study First Submitted QC: 2024-06-28
• Study First Posted: 2024-07-05
• Study Start: 2025-04-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-14
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 686

Inclusion Criteria

1. Age ≥65 years old.
2. Having a scheduled surgery (≥2 hours, general anesthesia) (e.g., total hip replacement, toal knee replacement, open reduction and internal fixation of hip and lumbar spine).
3. Being able to complete neuropsychological tests, 3D-CAM and CAM-S.
4. Chinese Mandarin as their native language.
5. Edmonton frailty scale (EFS) score ≥ 6.

Exclusion Criteria

1. Having delirium, assessed by 3D-CAM, before surgery.
2. Having a brain tumour, stroke or mental disorders (eg, major depressive disorder or dementia).
3. Participating in other clinical studies at the time of screening.
4. Unwillingness to comply with the protocol or procedures.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Incidence of postoperative delirium	at baseline and postoperative day 1 to 3	The presence of postoperative delirium will be defined according to 3D-CAM, which includes four entries: acute onset and fluctuating course, inattention, disorganized thinking and altered level of consciousness. To diagnose delirium, both the first and second criteria have to be present plus the third and/or fourth criteria. Every participant will be assessed twice daily after anesthesia/surgery from postoperative day 1 to postoperative day 3, with the first assessment between 8:00 and 10:00. The second assessment will be between 15:00 and 17:00.

Secondary Outcome Measures

Name	Time	Method
Incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder	at baseline, on 21 days and 6 months after anesthesia/surgery	Participants' cognitive function will be assessed at baseline, on postoperative day 21, and at postoperative month 6 using a battery of neuropsychological tests, including the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test Retention (HVLTRet), Hopkins Verbal Learning Test Total Recall (HVLTTR), Brief Visuospatial Memory Test Total Recall (BVMTTR), Brief Visuospatial Memory Test Delayed Recall (BVMTDR), Benton Judgment of Line Orientation (JLO), Digit Span Test (DST), Verbal Fluency Test (VFT) and Trail Making Test (TMT). Cognitive Change Index will be calculated by subtracting baseline scores from postoperative scores in each of the neuropsychological tests. Delayed neurocognitive recovery or postoperative neurocognitive disorder will be defined as by a decrease by one or more standard deviations in at least two of the neuropsychological tests from the baseline to 21 days or 6 months after anesthesia/surgery.

Trial Locations

Locations (1)

Shanghai Tenth People's Hospital; 🇨🇳 Shanghai, China