Sleep and Circadian Rhythm Biomarkers of Postoperative Delirium

NCT06052397 | Recruiting

• 1 other identifier: 2023P000596
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective cohort study is to assess potential differences in sleep biomarkers in older adult patients undergoing major orthopedic surgery. The main questions it aims to answer are:

1. 1.To define sleep/circadian biomarkers of delirium (sleep duration, regularity, stability and timing of rhythm) in a prospective observational study.
2. 2.To determine if plasma Alzheimer's disease (AD) pathology/inflammatory burden interacts with or moderates the relationship between a sleep/circadian biomarker and post-operative delirium (POD) risk.
3. 3.To determine whether sleep/circadian regulation interacts with the genetic risk of AD to influence POD/cognitive decline.
4. 4.Donate several blood samples both intraoperatively and postoperatively
5. 5.Complete baseline and postoperative neurocognitive assessments
6. 6.Wear an actigraphy data collection watch for the two weeks prior to their surgery

Conditions

Delirium, Postoperative; Cognitive Decline; Dementia

Keywords

Sleep; Postoperative Delirium; Circadian Rhythms; Cognition; Dementia

Outcome Measures

Primary Outcomes (1)

• Incidence of Delirium

  Outcome will be assessed using the Confusion Assessment Method (CAM)

  From postoperative day 1 to postoperative day 3

Secondary Outcomes (15)

• Severity of Delirium

  From postoperative day 1 to postoperative day 3

• Delirium-free Days

  Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5

• Postoperative Cognitive Status

  Months 1, 3, and 12 after surgery

• Postoperative Insomnia Symptom Severity

  Baseline and months 1, 3, and 12 after surgery

• Postoperative Sleep Quality

  Baseline and months 1, 3, and 12 after surgery

Other Outcomes (1)

• Length of Hospital Stay

  Date of hospital admission up until date of discharge, assessed up to 30 days

Study Arms (1)

Sleep and Circadian Rhythms biomarker cohort

Cohort will complete a series of blood sample donations (both intraoperatively and postoperatively) as well as complete daily neurocognitive assessments at baseline and on PODs 1 - 3.

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The Targeted/Planned enrollment for the proposed clinical study is consistent with the ethnic and racial composition of Suffolk County, MA. Please see below. American Indian and Alaska Native - 0.7 Native Hawaiian and Other Pacific Islander - 0.2 Asian - 9.3 Black, not Hispanic or Latino - 24.3 White, not Hispanic or Latino - 45.2 Hispanic or Latino - 23.3 Two or more races - 3.7 Female - 51.7

You may qualify if:

• Age \>= 70 years old
• Scheduled to undergo major orthopedic surgery
• Expected postoperative recovery of more than 24 hours as an inpatient

You may not qualify if:

• Cognitive impairment leading to inability to consent
• Patients with limited mobility or inability to wear an actigraphy watch
• Patients with infection at the site of actigraphy watch, allergies to materials of watch
• Patients with \> two days in the ICU during the month prior to surgery
• Renal or liver failure
• Severe neurocognitive damage or history of psychiatric illness
• Blindness or deafness
• Patients who are non-English speaking

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (10)

• Ulsa MC, Xi Z, Li P, Gaba A, Wong PM, Saxena R, Scheer FAJL, Rutter M, Akeju O, Hu K, Gao L. Association of Poor Sleep Burden in Middle Age and Older Adults With Risk for Delirium During Hospitalization. J Gerontol A Biol Sci Med Sci. 2022 Mar 3;77(3):507-516. doi: 10.1093/gerona/glab272.

  PMID: 34558609 BACKGROUND

• Dessap AM, Roche-Campo F, Launay JM, Charles-Nelson A, Katsahian S, Brun-Buisson C, Brochard L. Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical Ventilation: An Ancillary Study of a Weaning Trial. Chest. 2015 Nov;148(5):1231-1241. doi: 10.1378/chest.15-0525.

  PMID: 26158245 BACKGROUND

• Miner B, Kryger MH. Sleep in the Aging Population. Sleep Med Clin. 2017 Mar;12(1):31-38. doi: 10.1016/j.jsmc.2016.10.008. Epub 2016 Dec 20.

  PMID: 28159095 BACKGROUND

• American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg. 2015 Feb;220(2):136-48.e1. doi: 10.1016/j.jamcollsurg.2014.10.019. Epub 2014 Nov 14. No abstract available.

  PMID: 25535170 BACKGROUND

• Gou RY, Hshieh TT, Marcantonio ER, Cooper Z, Jones RN, Travison TG, Fong TG, Abdeen A, Lange J, Earp B, Schmitt EM, Leslie DL, Inouye SK; SAGES Study Group. One-Year Medicare Costs Associated With Delirium in Older Patients Undergoing Major Elective Surgery. JAMA Surg. 2021 May 1;156(5):430-442. doi: 10.1001/jamasurg.2020.7260.

  PMID: 33625501 BACKGROUND

• Rahman S, Byatt K. Follow-up services for delirium after COVID-19-where now? Age Ageing. 2021 May 5;50(3):601-604. doi: 10.1093/ageing/afab014.

  PMID: 33951153 BACKGROUND

• Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009 Apr;5(4):210-20. doi: 10.1038/nrneurol.2009.24.

  PMID: 19347026 BACKGROUND

• O'Gara BP, Gao L, Marcantonio ER, Subramaniam B. Sleep, Pain, and Cognition: Modifiable Targets for Optimal Perioperative Brain Health. Anesthesiology. 2021 Dec 1;135(6):1132-1152. doi: 10.1097/ALN.0000000000004046.

  PMID: 34731233 BACKGROUND

• Gao L, Li P, Gaykova N, Zheng X, Gao C, Lane JM, Saxena R, Scheer FAJL, Rutter MK, Akeju O, Hu K. Circadian Rest-Activity Rhythms, Delirium Risk, and Progression to Dementia. Ann Neurol. 2023 Jun;93(6):1145-1157. doi: 10.1002/ana.26617. Epub 2023 Mar 3.

  PMID: 36808743 BACKGROUND

• Sugg E, Gleeson E, Baker SN, Li P, Gao C, Mueller A, Deng H, Shen S, Franco-Garcia E, Saxena R, Musiek ES, Akeju O, Xie Z, Hu K, Gao L. Sleep and circadian biomarkers of postoperative delirium (SLEEP-POD): protocol for a prospective and observational cohort study. BMJ Open. 2024 Apr 19;14(4):e080796. doi: 10.1136/bmjopen-2023-080796.

  PMID: 38643014 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Emergence Delirium; Cognitive Dysfunction; Dementia

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Brain Diseases; Central Nervous System Diseases

Study Officials

• Lei Gao, MBBS

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lei Gao, MBBS

CONTACT

(617)888-2941; lgao@mgh.harvard.edu

Elizabeth Gleeson, BS

CONTACT

(650)704-6458; egleeson1@mgh.harvard.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Department of Anesthesia, Critical Care, and Pain Medicine

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: September 25, 2023
• Study Start: September 12, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data may be shared with collaborators once the study has been completed.
• Access Criteria: IRB approved research team members or approved collaborators within MGB.

Locations

US (1)