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

NCT04575753 | Withdrawn DMC

• 1 other identifier: Resolvin-delirium
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Delirium

Outcome Measures

Primary Outcomes (3)

• The influence of serum levels of resolvins (RvD1) at ICU admission, and ICU day 2 and day 5 on cognitive impairment (defined by CAM-ICU) on day 5 of ICU stay.

  Blood samples will be drawn at the day of ICU admission, day 2 and day 5 after ICU admission to measure resolvins (RvD1; 17SHDHA; DHA) through mass spectrometry. At the same timepoints, cognitive testing will be performed (CAM-ICU) to determine the presence or absence of delirium on day 5 of ICU admission.

  5 days

• The influence of serum levels of resolvins (DHA) at ICU admission, and ICU day 2 and day 5 on cognitive impairment (defined by CAM-ICU) on day 5 of ICU stay.

  Blood samples will be drawn at the day of ICU admission, day 2 and day 5 after ICU admission to measure resolvins (RvD1; 17SHDHA; DHA) through mass spectrometry. At the same timepoints, cognitive testing will be performed (CAM-ICU) to determine the presence or absence of delirium on day 5 of ICU admission.

  5 days

• The influence of serum levels of resolvins (17SHDHA)) at ICU admission, and ICU day 2 and day 5 on cognitive impairment (defined by CAM-ICU) on day 5 of ICU stay.

  Blood samples will be drawn at the day of ICU admission, day 2 and day 5 after ICU admission to measure resolvins (RvD1; 17SHDHA; DHA) through mass spectrometry. At the same timepoints, cognitive testing will be performed (CAM-ICU) to determine the presence or absence of delirium on day 5 of ICU admission.

  5 days

Secondary Outcomes (25)

• Inflammatory markers-delirium-day0

  1 day

• Inflammatory markers-delirium-day0

  1 day

• Inflammatory markers-delirium-day0

  1 day

• Inflammatory markers-delirium-day0

  1 day

• Inflammatory markers-delirium-day0

  1 day

Interventions

Study group OTHER

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Non-ventilated, non-sedated adult patients of all genders with a planned ICU stay \>72 hours at the CHU de Charleroi, Charleroi, Belgium between October 2020- May 2021 will be included in this study.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Université Libre de Bruxelles: lead
• CHU de Charleroi: collaborator

Study Sites (1)

CHU-Charleroi Hopital Civil Marie Curie

Charleroi, Hainaut, Belgium

Location

Related Publications (13)

• 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.

  PMID: 11445689 BACKGROUND

• 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.

  PMID: 22091567 BACKGROUND

• 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.

  PMID: 11154118 BACKGROUND

• 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.

  PMID: 24162463 BACKGROUND

• 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.

  PMID: 29452810 BACKGROUND

• 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.

  PMID: 22190370 BACKGROUND

• 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.

  PMID: 20818791 BACKGROUND

• 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.

  PMID: 28405620 BACKGROUND

• 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.

  PMID: 31049563 BACKGROUND

• 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.

  PMID: 30772915 BACKGROUND

• 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.

  PMID: 30770053 BACKGROUND

• 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.

  PMID: 23709617 BACKGROUND

• 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.

  PMID: 32055250 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Delirium

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Michael Piagnerelli, MD; PHD

  CHU de Charleroi, Belgium

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anesthesiologist, principal investigator

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: October 5, 2020
• Study Start: October 7, 2023
• Primary Completion: May 30, 2024
• Study Completion: June 30, 2024
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)