Mechanistic Study of PK2 Pathway in Alleviating Perioperative Neurocognitive Disorders by Improving Neurometabolic Uncoupling

NCT07652008 | Not Yet Recruiting

• 2 other identifiers: KY20260402-01ZKX21038
• Study Type: observational
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

The term perioperative neurocognitive disorders (PND) is derived from postoperative cognitive dysfunction (POCD), and has been renamed as PND in recent years in accordance with the latest international consensus. PND specifically refers to changes in mental, social and cognitive abilities in patients following surgery; in severe cases, personality changes and reduced social functioning may also occur. As a serious complication affecting the central nervous system (CNS), apart from surgical trauma, advanced age is widely recognized as a critical factor contributing to the development and progression of PND. Its adverse effects represent a major challenge for the rapidly growing elderly population worldwide. It is currently believed that the decline in cognitive functions such as memory and attention observed in some patients after surgery may be associated with inflammatory responses in the brain. Surgical stress may activate supporting cells in the brain, such as astrocytes. When these cells are abnormally activated, they may fail to maintain normal neuronal function, thereby disrupting brain homeostasis and leading to cognitive impairment. Recent studies have shown that these glial cells exert distinct effects on neurons under different phenotypes: some phenotypes promote neural repair and protection, whereas others exacerbate neural injury. Evidence suggests that in multiple neurological disorders, the pro-inflammatory phenotype of glial cells is closely associated with cognitive impairment. Prokineticin-2 (PK2) is an endogenous signaling molecule involved in the regulation of diverse physiological processes, including inflammatory responses, energy metabolism, and neuroprotection. Previous studies have demonstrated that PK2 exerts protective effects in various neurological disease models, improving neuronal function and alleviating cognitive or motor deficits. Our preliminary animal experiments revealed reduced brain PK2 levels, especially in memory-related regions, in mice with postoperative cognitive dysfunction. Exogenous supplementation of PK2 significantly restored brain cell function and improved cognitive performance in these mice, suggesting that PK2 may play an important role in maintaining cerebral function after surgery. However, it remains unclear whether changes in PK2 levels in clinical patients correlate with the occurrence and severity of postoperative cognitive dysfunction. This study aims to investigate changes in circulating PK2 levels and explore their association with postoperative cognitive alterations, so as to provide evidence for the improved prevention and identification of PND. We plan to enroll elderly patients undergoing hip replacement surgery at Nanjing First Hospital. By analyzing PK2 expression levels and dynamic changes, combined with postoperative neuropsychological scale assessments, we will evaluate the correlation between serum PK2 levels and the clinical incidence of PND, and further verify the intrinsic link between PK2 levels and the pathogenesis of PND.

Conditions

Perioperative Neurocognitive Disorders

Keywords

PND; PK2; Hip replacement surgery

Outcome Measures

Primary Outcomes (1)

• PK2 level

  Venous blood samples will be collected from patients 1 day before surgery and on postoperative days 1 and 3 for the detection of PK2 levels

  1 day before surgery and on postoperative days 1 and 3

Secondary Outcomes (5)

• the levels of related oxidative markers including SOD

  1 day before surgery and on postoperative days 1 and 3

• the levels of related oxidative markers including GSH

  1 day before surgery and on postoperative days 1 and 3

• the levels of related oxidative markers including CAT

  1 day before surgery and on postoperative days 1 and 3

• Levels of inflammatory markers TNF-α

  1 day before surgery and on postoperative days 1 and 3

• Levels of inflammatory markers IL-1β

  1 day before surgery and on postoperative days 1 and 3

Study Arms (2)

PND group

Perioperative neurocognitive disorder (PND) developed as an adverse event during postoperative follow-up following hip replacement surgery.

non-PND group

No perioperative neurocognitive disorder (PND) occurred during follow-up after hip replacement surgery.

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of elderly patients aged 65 to 80 years with ASA physical status Class Ⅰ-Ⅲ who are undergoing hip replacement surgery. Patients are excluded if they have an MMSE score ≤ 24, severe cardiac, pulmonary, hepatic or renal dysfunction, recent use of sedatives/antidepressants or alcohol abuse, severe mental disorders (e.g., depression, schizophrenia, bipolar disorder, mental retardation), a history of severe craniocerebral injury, cerebrovascular disease, hydrocephalus, intracranial tumor or other neurological diseases (e.g., Parkinson's disease, Huntington's disease, epilepsy), severe visual or hearing impairment, or inability to complete cognitive function tests due to advanced age, low educational level or other factors.

You may qualify if:

• Age ≥ 65 years and ≤ 80 years
• ASA physical status Class Ⅰ-Ⅲ
• Elderly patients undergoing hip replacement surgery

You may not qualify if:

• Mini-Mental State Examination (MMSE) score ≤ 24
• Severe cardiac, pulmonary, hepatic or renal dysfunction
• Recent use of sedatives or antidepressants, or alcohol abuse
• Patients with severe mental disorders including depression, schizophrenia, bipolar disorder, mental retardation, etc.
• History of severe craniocerebral injury, cerebrovascular disease, hydrocephalus, intracranial tumor, or other neurological diseases (e.g., Parkinson's disease, Huntington's disease, epilepsy)
• Severe visual or hearing impairment
• Inability to complete cognitive function tests due to advanced age, low educational level, or other factors

Sponsors & Collaborators

• Nanjing First Hospital, Nanjing Medical University: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

Study Officials

• Xiaoliang Wang, MD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yajie Xu, MD

CONTACT

86 18651815258; xuyajiechina@163.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 16, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: June 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share