DeliriumAPOCOGNITNCT02574234
Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies (APOCOGNIT)
A study testing Determination of apelin and inflammatory cytokines, Assessment of cognitive functions and Liquid sampling cerebrospinal in people with Delirium, run by University Hospital, Toulouse at 1 site in France.
Trial summary
No successful strategy is proposed to patients submitted to important surgery to reduce the incidence of postoperative cognitive disorders (POCD) onset. This project propose to measure plasma levels of apelin in wide population submitted to orthopedic surgery. Apelin could be involved in anti-inflammatory processes. Read more about this study
- Who is it for?
- Ages 75 years and older
- Conditions the study is for
- Delirium
- What is being tested?
- Determination of apelin and inflammatory cytokines, Assessment of cognitive functions and Liquid sampling cerebrospinal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteFrance
- Study dates
- 30 Mar 2016to 12 Mar 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 75 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients submitted to a programed orthopedic surgery
- Patients with pre- and post-surgery check-up.
Who cannot join
- Non programed orthopedic surgery (emergency)
- Patients with sepsis
- Patients submitted to orthopedic surgery but with ambulatory management.
- Existence of justice backup, curators or supervision.
- Absence of indication for a pre- or post-surgery check-up.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies
No successful strategy is proposed to patients submitted to important surgery to reduce the incidence of postoperative cognitive disorders (POCD) onset. This project propose to measure plasma levels of apelin in wide population submitted to orthopedic surgery. Apelin could be involved in anti-inflammatory processes. Apelin levels before and after surgery correlated to postoperative cognitive disorders symptom measured by PET-Scan could be an important predictive or diagnostic marker to adapt therapeutic strategy to fight against postoperative cognitive disorders.
Read the detailed description
It has been now clearly shown that important surgery with general anesthesia could be strongly associated to postoperative cognitive disorders few months after the intervention especially in elderlies. No strategy is really efficient to fight against this phenomenon that could lead to Alzheimer disease development. In order to prognosticate and characterize the potential risk to develop cognitive troubles after a surgery, this study propose to evaluate the potential predictive capacity of apelin in a cohort of young and old adult undergoing an orthopedic surgery. Apelin is a peptide involved in different physiological as well physiopathological pathways. This peptide, involved in osteogenesis and inflammatory processes, has also been described to be neuroprotective. Yet, hippocampic neuroinflammation has been related in case of postoperative cognitive disorders in human as well as in mice model of surgery. Taken together, these results seem to indicate that apelin could be a therapeutic target and be predictive of the postoperative cognitive disorders onset.
This study will measure plasma apelin levels in young and old adult one day before and after a programed orthopedic surgery. Moreover, to correlate apelin amounts with inflammation processes, protocol will quantify inflammatory cytokines in plasma (IL6, IL1, TNFα). These results will be compared to measures of brain b-amyloid deposit assessed by PET-Scan technology.
The follow-up of the patients will be done during 3 months in order to evaluate the postoperative cognitive disorders or the cognitive troubles associated to surgery (memory fail, decrease of cognitive reserve…).
- Conditions
- Delirium
- Being tested
- Determination of apelin and inflammatory cytokines, Assessment of cognitive functions, Liquid sampling cerebrospinal, Postoperative delirium research, Residual cognitive dysfunction research
- Keywords
- Postoperative cognitive disorders POCD, inflammation, Surgery
- Medical subject headings
- Delirium, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Determination of apelin and inflammatory cytokinesOther
A blood sample will be conducted at baseline, on day 1 and day 7 post operative to meter inflammatory cytokines (IL1B, IL1-ra, IL6) and apelin.
Assessment of cognitive functionsOther
Evaluation of preoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale.
Liquid sampling cerebrospinalOther
Determination of the concentrations of inflammatory cytokines and apelin in cerebrospinal fluid perioperatively.
Postoperative delirium researchOther
Using the scale Confusion Assessment Method (CAM) for screening and delirium diagnosis. This research will be daily lasted, during the first 7 days postoperative.
Residual cognitive dysfunction researchOther
Evaluation of postoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale realised on day 1 and day 7 postoperative. Realization of the IQCODE and IADL three months after the operation in a telephone interview.
| Study group | Role | What they receive |
|---|---|---|
| Patients with orthopedic surgery | Experimental | Patients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL).
Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE).
3 months after operation: evaluation of cognitive performance (IQCODE, IADL) Receives: Other: Determination of apelin and inflammatory cytokines; Other: Assessment of cognitive functions; Other: Liquid sampling cerebrospinal; Other: Postoperative delirium research; Other: Residual cognitive dysfunction research |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative delirium occurrence.
Evaluation of the occurrence of postoperative delirium evaluated by the Confusion Assessment Method (CAM)
Measured: day1 to day 7 post-operation
Secondary outcomes (5)
Evaluation of postoperative cognitive functions.
Evaluation with IQCODE questionary (Informant Questionary on Cognitive Decline in the Elderly)
Measured: day 1 to day 7 and 3 month after post-operation
Assessment of the autonomy.
Evaluation with IADL scale (Instrumental Activities Scale of Everyday Life)
Measured: day 1 to day 7 and 3 month after post-operation
Plasma concentration of apelin.
Measured: day 1 to day 7 post operation
Plasma concentration of inflammatory cytokines.
Measured: 24 hours before operation, day 1 to day 7 post operation
Concentration of inflammatory cytokines and apelin in the cerebrospinal fluid.
Measured: day 0 (operation day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2015 (estimated)
- Study start30 Mar 2016
- Primary completionMar 2018
- Study completion12 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent MINVILLE, MD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02574234
- Sponsor's protocol ID
- RC31/14/7313
- Acronym
- APOCOGNIT
- Status last verified
- Feb 2024
- First submitted
- 26 Aug 2015
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Silverstein JH, Timberger M, Reich DL, Uysal S. Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesthesiology. 2007 Mar;106(3):622-8. doi: 10.1097/00000542-200703000-00026. No abstract available.
PubMed 17325520Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291.
PubMed 20007989Price CC, Garvan CW, Monk TG. Type and severity of cognitive decline in older adults after noncardiac surgery. Anesthesiology. 2008 Jan;108(1):8-17. doi: 10.1097/01.anes.0000296072.02527.18.
PubMed 18156877Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.
PubMed 22762316Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010 Sep;68(3):360-8. doi: 10.1002/ana.22082.
PubMed 20818791Labaste F, Delort F, Ferre F, Bounes F, Reina N, Valet P, Dray C, Minville V. Postoperative delirium is a risk factor of institutionalization after hip fracture: an observational cohort study. Front Med (Lausanne). 2023 Aug 15;10:1165734. doi: 10.3389/fmed.2023.1165734. eCollection 2023.
PubMed 37649978
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies
- ClinicalTrials.gov ID
- NCT02574234
- Acronym / sponsor ID
- APOCOGNIT / RC31/14/7313
- Conditions
- Delirium
- Keywords
- Postoperative cognitive disorders POCD, inflammation, Surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 30 Mar 2016 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- 12 Mar 2018 (actual)
- First posted
- 12 Oct 2015 (estimated)
- 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.
No successful strategy is proposed to patients submitted to important surgery to reduce the incidence of postoperative cognitive disorders (POCD) onset. This project propose to measure plasma levels of apelin in wide population submitted to orthopedic surgery. Apelin could be involved in anti-inflammatory processes. Apelin levels before and after surgery correlated to postoperative cognitive disorders symptom measured by PET-Scan could be an important predictive or diagnostic marker to adapt therapeutic strategy to fight against postoperative cognitive disorders.
Detailed description
It has been now clearly shown that important surgery with general anesthesia could be strongly associated to postoperative cognitive disorders few months after the intervention especially in elderlies. No strategy is really efficient to fight against this phenomenon that could lead to Alzheimer disease development. In order to prognosticate and characterize the potential risk to develop cognitive troubles after a surgery, this study propose to evaluate the potential predictive capacity of apelin in a cohort of young and old adult undergoing an orthopedic surgery. Apelin is a peptide involved in different physiological as well physiopathological pathways. This peptide, involved in osteogenesis and inflammatory processes, has also been described to be neuroprotective. Yet, hippocampic neuroinflammation has been related in case of postoperative cognitive disorders in human as well as in mice model of surgery. Taken together, these results seem to indicate that apelin could be a therapeutic target and be predictive of the postoperative cognitive disorders onset.
This study will measure plasma apelin levels in young and old adult one day before and after a programed orthopedic surgery. Moreover, to correlate apelin amounts with inflammation processes, protocol will quantify inflammatory cytokines in plasma (IL6, IL1, TNFα). These results will be compared to measures of brain b-amyloid deposit assessed by PET-Scan technology.
The follow-up of the patients will be done during 3 months in order to evaluate the postoperative cognitive disorders or the cognitive troubles associated to surgery (memory fail, decrease of cognitive reserve…).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with orthopedic surgery | Experimental | Other: Determination of apelin and inflammatory cytokines, Other: Assessment of cognitive functions, Other: Liquid sampling cerebrospinal, Other: Postoperative delirium research, Other: Residual cognitive dysfunction researchPatients will be included in the consultation of anesthesia. The usual laboratory tests will be carried out and a determination of apelin and inflammatory cytokines. Assessment of cognitive functions using the Informant Questionnaire on Cognitive Decline in the Elderly (ICQODE), Mini Mental State examination (MMS) and the scale of Instrumental activities of daily living (IADL). Day of surgery: liquid sampling cerebrospinal. Day 1 to day 7 postoperatively: determination of inflammatory cytokines and apelin, postoperative delirium research (Confusion Assessment Method (CAM)), residual cognitive dysfunction research (MMS, IADL, IQCODE). 3 months after operation: evaluation of cognitive performance (IQCODE, IADL) |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Patients submitted to a programed orthopedic surgery
- Patients with pre- and post-surgery check-up.
Key exclusion criteria (5 listed)
- Non programed orthopedic surgery (emergency)
- Patients with sepsis
- Patients submitted to orthopedic surgery but with ambulatory management.
- Existence of justice backup, curators or supervision.
- Absence of indication for a pre- or post-surgery check-up.
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 |
|---|---|---|
| Determination of apelin and inflammatory cytokinesA blood sample will be conducted at baseline, on day 1 and day 7 post operative to meter inflammatory cytokines (IL1B, IL1-ra, IL6) and apelin. | Other | Patients with orthopedic surgery |
| Assessment of cognitive functionsEvaluation of preoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale. | Other | Patients with orthopedic surgery |
| Liquid sampling cerebrospinalDetermination of the concentrations of inflammatory cytokines and apelin in cerebrospinal fluid perioperatively. | Other | Patients with orthopedic surgery |
| Postoperative delirium researchUsing the scale Confusion Assessment Method (CAM) for screening and delirium diagnosis. This research will be daily lasted, during the first 7 days postoperative. | Other | Patients with orthopedic surgery |
| Residual cognitive dysfunction researchEvaluation of postoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale realised on day 1 and day 7 postoperative. Realization of the IQCODE and IADL three months after the operation in a telephone interview. | Other | Patients with orthopedic surgery |
Primary outcome
Postoperative delirium occurrence.
Time frame: day1 to day 7 post-operation
Evaluation of the occurrence of postoperative delirium evaluated by the Confusion Assessment Method (CAM)
5 secondary outcomes
Evaluation of postoperative cognitive functions.
Time frame: day 1 to day 7 and 3 month after post-operation
Assessment of the autonomy.
Time frame: day 1 to day 7 and 3 month after post-operation
Plasma concentration of apelin.
Time frame: day 1 to day 7 post operation
Plasma concentration of inflammatory cytokines.
Time frame: 24 hours before operation, day 1 to day 7 post operation
Concentration of inflammatory cytokines and apelin in the cerebrospinal fluid.
Time frame: day 0 (operation day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Background: PubMed 17325520Silverstein JH, Timberger M, Reich DL, Uysal S. Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesthesiology. 2007 Mar;106(3):622-8. doi: 10.1097/00000542-200703000-00026. No abstract available.
- Background: PubMed 20007989Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291.
- Background: PubMed 18156877Price CC, Garvan CW, Monk TG. Type and severity of cognitive decline in older adults after noncardiac surgery. Anesthesiology. 2008 Jan;108(1):8-17. doi: 10.1097/01.anes.0000296072.02527.18.
- Background: PubMed 22762316Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.
- Background: PubMed 20818791Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010 Sep;68(3):360-8. doi: 10.1002/ana.22082.
- Results publication: PubMed 37649978Labaste F, Delort F, Ferre F, Bounes F, Reina N, Valet P, Dray C, Minville V. Postoperative delirium is a risk factor of institutionalization after hip fracture: an observational cohort study. Front Med (Lausanne). 2023 Aug 15;10:1165734. doi: 10.3389/fmed.2023.1165734. eCollection 2023.
- 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. This study is not recruiting at the moment.
Vincent MINVILLE, MD principal investigator
University Hospital, Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Determination of apelin and inflammatory cytokines, Assessment of cognitive functions and Liquid sampling cerebrospinal in people with Delirium, run by University Hospital, Toulouse at 1 site in France.
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 2 inclusion and 5 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: finished, as of the sponsor's last update on 28 Feb 2024. 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 France. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative delirium occurrence. (time frame: day1 to day 7 post-operation). 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 NCT02574234, which also lists 6 linked publications.
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 28 Feb 2024.