Perioperative Neurocognitive DisorderNCT06488807
Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment
A study testing Olfactory Enrichment in people with Perioperative Neurocognitive Disorder, run by Shanghai 10th People's Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Perioperative Neurocognitive Disorder
- What is being tested?
- Olfactory Enrichment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 686 participants
- Where
- 1 siteChina
- Study dates
- 7 Apr 2025to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanghai Tenth People's Hospital
Shanghai
Yuan Shen
About this study
Official title: Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment: Study Protocol for a Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Perioperative Neurocognitive Disorder
- Being tested
- Olfactory Enrichment, Sham
- Keywords
- Perioperative Neurocognitive Disorder, Odor Enrichment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olfactory EnrichmentOther
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.
ShamOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at baseline and postoperative day 1 to 3
Secondary outcomes (1)
Incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder
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.
Measured: at baseline, on 21 days and 6 months after anesthesia/surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2024
- Study start7 Apr 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Perioperative Neurocognitive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 686 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai 10th People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Natural Science Foundation of China
- Responsible party
- Principal investigator, Yuan Shen, MD, PhD, Shanghai 10th People's Hospital
- Investigators
- Yuan Shen, Principal investigator, Shanghai Mental Health Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06488807
- Sponsor's protocol ID
- dsyy008
- Status last verified
- May 2025
- First submitted
- 15 Jun 2024
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41013688
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment: Study Protocol for a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06488807
- Acronym / sponsor ID
- dsyy008
- Conditions
- Perioperative Neurocognitive Disorder
- Keywords
- Perioperative Neurocognitive Disorder, Odor Enrichment
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 686 participants (estimated)
- Lead sponsor
- Shanghai 10th People's HospitalUniversity, hospital or other
- Collaborators
- National Natural Science Foundation of China
- Study start
- 7 Apr 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 5 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olfactory Enrichment Group | Experimental | Other: Olfactory EnrichmentAll 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. |
| Sham Group | Sham comparator | Other: ShamThe 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olfactory EnrichmentEach 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. | Other | Olfactory Enrichment Group |
| ShamThe 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 Group |
Primary outcome
Incidence of postoperative delirium
Time frame: 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.
1 secondary outcome
Incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder
Time frame: at baseline, on 21 days and 6 months after anesthesia/surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Derived from this study: PubMed 41013688Mei 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yuan Shen principal investigator
Shanghai Mental Health Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Olfactory Enrichment in people with Perioperative Neurocognitive Disorder, run by Shanghai 10th People's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuan Shen (+8618602169932, dr.yuanshen@foxmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of postoperative delirium (time frame: at baseline and postoperative day 1 to 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06488807, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.