Clinical trial NCT02574234: Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies (APOCOGNIT)
Official title: Influence of Apelin Levels on Postoperative Cognitive Disorders After Orthopedic Surgery in Elderlies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Delirium
Keywords: Postoperative cognitive disorders POCD
inflammation
Surgery
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2015-10-12
Enrollment: 88
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

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...).

Eligibility criteria: 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.

Primary outcomes:
measure: Postoperative delirium occurrence.
timeFrame: day1 to day 7 post-operation
Secondary outcomes:
measure: Evaluation of postoperative cognitive functions.
timeFrame: day 1 to day 7 and 3 month after post-operation
measure: Assessment of the autonomy.
timeFrame: day 1 to day 7 and 3 month after post-operation
measure: Plasma concentration of apelin.
timeFrame: day 1 to day 7 post operation
measure: Plasma concentration of inflammatory cytokines.
timeFrame: 24 hours before operation, day 1 to day 7 post operation
measure: Concentration of inflammatory cytokines and apelin in the cerebrospinal fluid.
timeFrame: day 0 (operation day)
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU Toulouse, service d'orthopédie et traumatologie
Study officials:
affiliation: CHU Toulouse
name: Vincent MINVILLE, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: 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.
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/fmed.2023.1165734. eCollection 2023.