Evaluating the Role of Pre-existing Resolvins in the Resolution of ICU Delirium

NCT ID: NCT04575753

Last Updated: 2025-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2023-10-07

Study Completion Date

2024-06-30

Brief Summary

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As patient management is improving, more and more ICU survivors are being confronted with cognitive dysfunction and this well after their hospital stay.

In the ICU, delirium rates have been reported to be as high at 81%. Delirium is associated with patient and family stress, increased hospital costs, increased duration of stay, escalation of care and increased mortality and morbidity.

The physiopathology of ICU cognitive impairment is complex and involves an inflammatory cascade Recently, the role of 'resolvins' derived from omega-3 fatty acids has been studied in the resolution of inflammation.

Therefore, this hypothesis of this study is that ICU patients with higher serum levels of resolvins at ICU admission, ICU day 2 and day 5 will have a lesser degree of cognitive impairment on day 5 of ICU stay.

Detailed Description

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As patient management is improving, more and more ICU survivors are being confronted with cognitive dysfunction and this well after their hospital stay.

Delirium is characterized by an acute onset or fluctuating course, inattention and either disorganized thought (manifesting as memory, language and orientation difficulties) or altered level of consciousness. Multiple forms exist: hyperactive versus hypoactive versus mixed.

In the ICU, delirium rates have been reported to be as high at 81%. Delirium is associated with patient and family stress, increased hospital costs, increased duration of stay, escalation of care and increased mortality and morbidity.

The physiopathology of ICU cognitive impairment is complex. One theory is that, during infection/trauma, the alarmin high molecular group box 1 (HMGB1) is released into the bloodstream by activated platelets.

This damage-associated molecular pattern (DAMP) can bind to pattern recognition receptors on circulating bone marrow-derived monocytes (BM-DMs), causing a platelet-monocyte interaction but also triggering the nuclear translocation of the transcription factor NF-kappaB which activates gene expression and release of pro-inflammatory cytokines. The onset of this inflammatory state disrupts the blood brain barrier.

Within the brain parenchyma the chemokine MCP-1 and, by signaling through its receptor, CCR2, attracts the BM-DMs. The influx of BM-DMs activates the resident quiescent microglia. Together, BM-DMs and activated microglia release HMGB1, IL-6, and IL-1β ; thereby disrupting long-term potentiation and the synaptic plasticity involved in cognitive functions of learning and memory.

Inability to successfully resolve the inflammatory cascade promotes the development of cognitive impairment.

Recently, the role of 'resolvins' derived from omega-3 fatty acids has been studied in the resolution of inflammation.

In a mouse model of perioperative neurocognitive disorder, maresin 1 (a metabolite of omega-3) improved post-operative cognition and prevented surgery-induced glial activation and opening of the blood brain barrier. Similarly, in the same model, aspirine-triggered resolving D1 improved post-operative cognition, reduced systemic IL-6 levels and reserved surgery-induced astrogliosis.

Mechanically ventilated ICU patients who benefitted from omega-3 supplements, had a lesser degree of ICU delirium.

Therefore, the hypothesis of this study is that ICU patients with higher serum levels of resolvins at ICU admission, ICU day 2 and day 5 will have a lesser degree of cognitive impairment on day 5 of ICU stay.

Conditions

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Delirium

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Study group

Blood samples will be taken from ICU patients on the day of ICU admission, day 2 and day 5 after ICU admission.

Similarly, patients will be subjected to cognitive testing (CAM-ICU) to determine the presence of delirium

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Non-ventilated, non-sedated adult patients with a planned ICU stay \>72 hours. - - patients admitted due to an exacerbation of COPD
* patients admitted due to severe trauma
* patients admitted due to cardiogenic shock
* patients admitted due to septic shock

Exclusion Criteria

* Patients who don't understand English, French or Dutch
* Patients who are visually/auditory impaired (without glasses/ hearing aid)
* Patients with known neuro-psychiatric disorders
* Patients with known recreational drug and alcohol (ab)use
* Patients with a neurological trauma
* Patients on ECMO
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CHU de Charleroi

OTHER

Sponsor Role collaborator

Université Libre de Bruxelles

OTHER

Sponsor Role lead

Responsible Party

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Sarah Saxena

Anesthesiologist, principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Piagnerelli, MD; PHD

Role: STUDY_CHAIR

CHU de Charleroi, Belgium

Locations

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CHU-Charleroi Hopital Civil Marie Curie

Charleroi, Hainaut, Belgium

Site Status

Countries

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Belgium

References

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Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR, Inouye SK. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001 Jul;29(7):1370-9. doi: 10.1097/00003246-200107000-00012.

Reference Type BACKGROUND
PMID: 11445689 (View on PubMed)

Leslie DL, Inouye SK. The importance of delirium: economic and societal costs. J Am Geriatr Soc. 2011 Nov;59 Suppl 2(Suppl 2):S241-3. doi: 10.1111/j.1532-5415.2011.03671.x.

Reference Type BACKGROUND
PMID: 22091567 (View on PubMed)

Rouhiainen A, Imai S, Rauvala H, Parkkinen J. Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation. Thromb Haemost. 2000 Dec;84(6):1087-94.

Reference Type BACKGROUND
PMID: 11154118 (View on PubMed)

Vacas S, Degos V, Tracey KJ, Maze M. High-mobility group box 1 protein initiates postoperative cognitive decline by engaging bone marrow-derived macrophages. Anesthesiology. 2014 May;120(5):1160-7. doi: 10.1097/ALN.0000000000000045.

Reference Type BACKGROUND
PMID: 24162463 (View on PubMed)

Hu J, Feng X, Valdearcos M, Lutrin D, Uchida Y, Koliwad SK, Maze M. Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice. Br J Anaesth. 2018 Mar;120(3):537-545. doi: 10.1016/j.bja.2017.11.096. Epub 2018 Feb 3.

Reference Type BACKGROUND
PMID: 29452810 (View on PubMed)

Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, Jonsson Fagerlund M, Charo IF, Akassoglou K, Maze M. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011 Dec;70(6):986-995. doi: 10.1002/ana.22664.

Reference Type BACKGROUND
PMID: 22190370 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20818791 (View on PubMed)

Feng X, Valdearcos M, Uchida Y, Lutrin D, Maze M, Koliwad SK. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice. JCI Insight. 2017 Apr 6;2(7):e91229. doi: 10.1172/jci.insight.91229.

Reference Type BACKGROUND
PMID: 28405620 (View on PubMed)

Saxena S, Lai IK, Li R, Maze M. Neuroinflammation is a putative target for the prevention and treatment of perioperative neurocognitive disorders. Br Med Bull. 2019 Jun 19;130(1):125-135. doi: 10.1093/bmb/ldz010.

Reference Type BACKGROUND
PMID: 31049563 (View on PubMed)

Ishihara T, Yoshida M, Arita M. Omega-3 fatty acid-derived mediators that control inflammation and tissue homeostasis. Int Immunol. 2019 Aug 23;31(9):559-567. doi: 10.1093/intimm/dxz001.

Reference Type BACKGROUND
PMID: 30772915 (View on PubMed)

Yang T, Xu G, Newton PT, Chagin AS, Mkrtchian S, Carlstrom M, Zhang XM, Harris RA, Cooter M, Berger M, Maddipati KR, Akassoglou K, Terrando N. Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders. Br J Anaesth. 2019 Mar;122(3):350-360. doi: 10.1016/j.bja.2018.10.062. Epub 2018 Dec 28.

Reference Type BACKGROUND
PMID: 30770053 (View on PubMed)

Terrando N, Gomez-Galan M, Yang T, Carlstrom M, Gustavsson D, Harding RE, Lindskog M, Eriksson LI. Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline. FASEB J. 2013 Sep;27(9):3564-71. doi: 10.1096/fj.13-230276. Epub 2013 May 24.

Reference Type BACKGROUND
PMID: 23709617 (View on PubMed)

Naghibi T, Shafigh N, Mazloomzadeh S. Role of omega-3 fatty acids in the prevention of delirium in mechanically ventilated patients. J Res Med Sci. 2020 Jan 20;25:10. doi: 10.4103/jrms.JRMS_567_18. eCollection 2020.

Reference Type BACKGROUND
PMID: 32055250 (View on PubMed)

Other Identifiers

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Resolvin-delirium

Identifier Type: -

Identifier Source: org_study_id

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