Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment

NCT06488807 | Recruiting DMC

• 1 other identifier: dsyy008
• Study Type: interventional
• Target: 686
• Locations: 1 country
• Sites: 1

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.

Conditions

Perioperative Neurocognitive Disorder

Keywords

Perioperative Neurocognitive Disorder; Odor Enrichment

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium

  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.

  at baseline and postoperative day 1 to 3

Secondary Outcomes (1)

• Incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder

  at baseline, on 21 days and 6 months after anesthesia/surgery

Other Outcomes (5)

• Severity of delirium

  at baseline and postoperative day 1 to 3

• Severity of delayed neurocognitive recovery and postoperative neurocognitive disorder

  at baseline, on 21 days and 6 months after anesthesia/surgery

• Activities of Daily Living

  at baseline, on 21 days and 6 months after anesthesia/surgery

Study Arms (2)

Olfactory Enrichment Group

EXPERIMENTAL

All participants enrolled in the olfactory enrichment group will receive twice sessions per day with an interval of at least 6 hours on preoperative day 1 and postoperative day 1-3. Each session will last 30 minutes. Each participant will be equipped with an electrical odor dispenser which allowed to distribute 8 odors (grapefruit, lavender, lemon, peppermint, tangerine, green tea, cloves and eucalyptus). When pushing a button, 4 odors will be released in turn and participants will sniff each odor (approximately 4 ml odorized air) for approximately 30 seconds by a nasal catheter. Considering of the adaption of odors, 4 odors will be used in the morning session and another 4 odors will be used in the afternoon session.

Other: Olfactory Enrichment

Sham Group

SHAM COMPARATOR

The sham group will receive sham olfactory enrichment sessions, which is designed with the same pattern (twice a day, 30 min for each session, on preoperative day 1 and on postoperative day 1-3. However, the containers provided to the sham group will be odorless. The odor containers and labels will appear identical to those used in the olfactory enrichment group.

Other: Sham

Interventions

Olfactory Enrichment OTHER

Each participant will be equipped with an electrical odor dispenser which allowed to distribute 8 odors (grapefruit, lavender, lemon, peppermint, menthol, tangerine, green tea, and bergamot). The choice of odors was guided by (1) pleasantness of the odors, (2) presence of slight trigeminal activation in some of the odors, e.g., peppermint, (3) evaporation characteristics, so that the odors would last for the duration of the experiment, (4) technical issues mostly in terms of compatibility with the odor cartridge, (5) availability, and (6) inspiration from the previous studies.

Olfactory Enrichment Group

Sham OTHER

The containers provided to the sham group will be odorless. The odor containers and labels will appear identical to those used in the olfactory enrichment group.

Sham Group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥65 years old.
• 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).
• Being able to complete neuropsychological tests, 3D-CAM and CAM-S.
• Chinese Mandarin as their native language.
• Edmonton frailty scale (EFS) score ≥ 6.

You may not qualify if:

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

Sponsors & Collaborators

• Shanghai 10th People's Hospital: lead
• National Natural Science Foundation of China: collaborator

Study Sites (1)

Shanghai Tenth People's Hospital

Shanghai, China

RECRUITING

Related Publications (1)

• Mei X, Wang J, Ni Z, Wang Y, Zhao B, Sessler DI, Xie Z, Shen Y. Effects of olfactory enrichment on perioperative neurocognitive disorders in elderly patients undergoing orthopedic surgery: a study protocol of a multi-center randomized controlled trial. Trials. 2025 Sep 26;26(1):363. doi: 10.1186/s13063-025-09109-w.

  PMID: 41013688 DERIVED

MeSH Terms

Interventions

salicylhydroxamic acid

Study Officials

• Yuan Shen

  Shanghai Mental Health Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuan Shen

CONTACT

+8618602169932; dr.yuanshen@foxmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: June 15, 2024
• First Posted: July 5, 2024
• Study Start: April 7, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)