Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies (APOCOGNIT)

Delirium Clinical Trial

— APOCOGNIT  

Official title:

Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02574234
• Other study ID #: RC31/14/7313
• Status: Completed
• Phase: N/A
• Start date: March 30, 2016
• Est. completion date: March 12, 2018

Study information

• Verified date: February 2024
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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…).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: March 12, 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

Inclusion Criteria:

• Patients submitted to a programed orthopedic surgery
• Patients with pre- and post-surgery check-up.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Delirium

Intervention

Other:
• Determination of apelin and inflammatory cytokines
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 functions
Evaluation of preoperative cognitive performance by achieving a IQCODE, an MMS and an IADL scale.
• Liquid sampling cerebrospinal
Determination of the concentrations of inflammatory cytokines and apelin in cerebrospinal fluid perioperatively.
• Postoperative delirium research
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 research
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.

Locations

Country	Name	City	State
France	CHU Toulouse, service d'orthopédie et traumatologie	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

References & Publications (6)

Cibelli 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. — View Citation

Deiner 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. — View Citation

Labaste 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/fme — View Citation

Price 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. — View Citation

Saczynski 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative delirium occurrence.	Evaluation of the occurrence of postoperative delirium evaluated by the Confusion Assessment Method (CAM)	day1 to day 7 post-operation
Secondary	Evaluation of postoperative cognitive functions.	Evaluation with IQCODE questionary (Informant Questionary on Cognitive Decline in the Elderly)	day 1 to day 7 and 3 month after post-operation
Secondary	Assessment of the autonomy.	Evaluation with IADL scale (Instrumental Activities Scale of Everyday Life)	day 1 to day 7 and 3 month after post-operation
Secondary	Plasma concentration of apelin.		day 1 to day 7 post operation
Secondary	Plasma concentration of inflammatory cytokines.		24 hours before operation, day 1 to day 7 post operation
Secondary	Concentration of inflammatory cytokines and apelin in the cerebrospinal fluid.		day 0 (operation day)