LINC01844 as a Diagnostic Biomarker for POCD in Elderly Patients

Postoperative Cognitive Dysfunction Clinical Trial

Official title:

Clinical Study on LINC01844 as a Diagnostic Marker for Early Postoperative Cognitive Dysfunction in Elderly Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06387836
• Other study ID #: B2024-063
• Status: Recruiting
• Start date: February 21, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: Shanghai Zhongshan Hospital
• Contact: Danfeng Jin, M.D.
• Phone: +8613795306154
• Email: jindanfeng0506[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Postoperative cognitive dysfunction (POCD) is a common complication after surgery that is associated with more adverse events and death. The goal of this observational study is to learn about the diagnosis performance of long intergenic non-coding RNA(LINC01844) level in blood of older people for POCD. The main question it aims to answer is:

Does the relative level of LINC01844 in blood help diagnose POCD of older people after surgery? Participants undergoing elective lumbar decompression and fusion will finish neuropsychological evaluations one day before and 1st, 3rd and 5th day after surgery. At the same timepoint, the relative level of LINC01844 in blood will also be tested.

Description:

Trial design This single-center, observational trial will be conducted during elective lumbar decompression and fusion at Zhongshan Hospital Fudan University, Shanghai, China. Written informed consent is obtained from all the participants. By Feb 21, 2024, the trial was approved for Zhongshan Hospital, Fudan University (China) with the approval number B2024-063R.

Anesthesia After the patients entered the operating room, the vital signs are monitored, the patients are given oxygen inhalation (> 8L/min). General anesthesia is induced with sufentanil (0.2ug/kg), propofol [target controlled infusion (TCI) at plasma concentration of 3ug/ml) , remifentanil(TCI at plasma concentration of 3 ng/ml) and rocuronium (0.6mg/kg). The narcotic and vasoactive drugs are used during the operation according to anesthesia depth, the blood pressure, and respiratory parameters. A patient-controlled intravenous analgesia (PCIA) pump (sufentanil 250ug, and ramosetron 0.6mg) is connected after the surgery.

Detection and preparation of LINC01844 Total RNA is extracted from peripheral blood samples using TRIzol LS (Invitrogen, USA) according to the instructions from the manufacturer. Briefly, after homogenizing the blood sample (250 μL) with TRIzol LS regent (750 μL), chloroform (200 μL) is added for further analysis. The sample is centrifuged at 12,000 × g, 4˚C for 15 min, then the aqueous phase containing the RNA is transferred to a new tube and isopropanol (0.5 mL) is added for RNA precipitation. The RNA pellet is washed by 75% ethanol (1 mL), and finally resuspended in RNase free water (10-20 μL), the RNA quality is determined with NanoDrop2000. An optical density ratio of 260/280 >1.80 is an indication that the sample could be used in subsequent experiments. Next, we use M-MLV reverse transcriptase (Promega, USA) for the synthesis of cDNA. A real-time quantitative polymerase chain reaction (qRT-PCR) was utilized for the final analysis according to the instructions from the SYBR Green PCR Master Mix Kit (Qiagen). The PCR parameters: 95˚C for 10 min; 45 cycles at 95˚C for 15 s, 60˚C for 30s, and 72˚C 30s. GAPDH is chosen as a reference gene, fold change (2 -44Ct ) is utilized to analyze LINC01844 relative levels.

Neuropsychological test evaluation and POCD assessment One day before surgery, patients will be assessed for depression using the patient health Questionnaire-9 (PHQ-9), while patients with previous severe cognitive impairment are excluded using the mini mental state examination (MMSE) (MMSE score < 24). A battery of neuropsychological tests will be performed 1 day before operation and 1st, 3rd and 5th day after operation to evaluate the cognitive function of patients, including Hopkins auditory learning test-revised (HALT-R), brief visuospatial memory test-revised (BVMT-R), trail making test (TMT), digit span test (DST), digital symbol substitution test (DSST) and verb and graph recall test. All these tests are performed in a quiet environment by a trained doctor who is blinded to the surgical procedure and blood sample. At the same time, 20 healthy volunteers without surgery will be recruited as the control group, with age, sex and education years matched. The neuropsychological test will be performed in control group to determine the normal reference value of cognitive function, with the same interval. Baseline scores and learning outcomes were subtracted from each neuropsychological test score according to the international guidelines for the study of postoperative cognitive impairment, and divided by the standard deviation of baseline scores in the control group. The result was designated a Z score. When at least two Z scales are greater than 1.961, POCD was considered.

Study visits and data collection Patients will be visited preoperatively and postoperative day (POD) 1 and 3 and 5. The patients will be screened according to the inclusion criteria. All patients meeting the inclusion criteria will be registered in a screening log file. The investigators will explain the course and purpose of the study and provide written information on the study. Patients willing to participate in the study will be required to provide written informed consent.

Data will be registered in both the paper case report form (CRF) and the electronic case report form (eCRF) on electronic data capture (EDC) system by trial or clinical personnel under the supervision of the trial site investigators. In the case of inconsistency, the paper CRF will be used as a gold standard.

Handling of data Two members of the research team will perform study monitoring. Remote monitoring will be performed to signal early aberrant patterns, issues with consistency, credibility, and other anomalies. Patient data will be collected in pseudonymous form using a patient (identification) number composed of four three digits. Study data will be collected and managed using an investigator-initiated trial EDC (IIT-EDC) tools. IIT-EDC is a password-protected, intranet-based application designed to support data record for research studies (website: http://10.15.7.137). Full access to the final trial dataset will be granted to selected investigators. All original records, including consent forms, reports of suspected unexpected serious adverse events (SAE), and relevant correspondences, will be archived at the trial sites for 10 years. The clean trial database file will be anonymized and maintained for 10 years.

Safety All adverse events (AE) thought to be related to the trial will be reported to the trial coordinating center. According to local laws and regulations, the participants may receive free treatment provided by our unit or be compensated if any injury related to this study does occur, and all suspected unexpected SAEs will be reported to the data monitoring and safety committee (DMSC). The DMSC is independent of the trial investigators and will perform an ongoing review of safety parameters and overall study conduct. The DMSC comprises two independent experts in large-scale clinical trials and one independent statistician. The DMSC will be responsible for safeguarding the interests of the trial participants, assessing the safety and efficacy of the interventions during the trial, and monitoring the overall conduct of the clinical trial. To enhance the integrity of the trial, the DMSC may also formulate recommendations relating to the recruitment/retention of participants, their management, improving adherence to protocol-specified regimens and retention of participants, and procedures for data management and quality control.

Statistical analysis Sample size -To verify the prediction value of the relative level of LINC01844 in blood for POCD of older people after surgery, area under the curve (AUC) measured via the receiver operating characteristic curve (ROC) needs to be more than 0.5. Based on results from preliminary trial, the AUC was 0.73 and the incidence of POCD was 33.3%. Sample size was calculated by PASS (version 11.0). For power of 80% and level of significance of 5% against the one-sided alternative hypothesis, 57 participants are required. Expecting 10% drop-out of participants, a sample size of 63 is required.

Analysis - Kolmogorov-Smirnov test will be used to assess the normal distribution of continuous data. The baseline characteristics will be expressed as counts and percentages, means and standard deviations, or medians and interquartile ranges, as appropriate. The independent predictors of POCD were analyzed by binary logistic regression, and the results were expressed as odds ratios (ORs). The prediction performance of LINC01844 for POCD will be measured using ROC, and the results were determined by the 95% confidence intervals and AUC. No or minimal losses to follow-up for the primary and secondary outcomes are anticipated. The intention-to-treat (ITT, all randomly assigned cases) population is used for all outcomes analysis. The supportive analysis is based on full analysis set (FAS, all randomly assigned patients who receive lumbar decompression and fusion). Complete-case analysis will be performed for all outcomes. However, if more than 1% of missing data are found for the primary outcome, a sensitivity analysis using multiple imputations and estimating equation methods will be carried out.

Cleaning and locking of the database The datasets used and/or analyzed during the current study will be made available from the corresponding author upon reasonable request. The database will be locked immediately after all data are entered and all discrepant or missing data are resolved, or, alternatively, if all efforts have been employed and we consider that the remaining issues cannot be fixed. In this step, the data will be reviewed before database locking. The study database will then be locked and exported for statistical analysis. At this stage, permission for access to the database will be removed for all investigators, and the database will be archived.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: June 30, 2025
• Est. primary completion date: February 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients scheduled to perform elective lumbar decompression and interbody fusion under general anesthesia;

• 65-85 years old;

• American Society of Anesthesiologists (ASA) physical status I-III level;

• Body mass index (BMI) between 20 Kg/m2 and 28 Kg/m2;

• From whom written informed consent is obtainable either from the patient or from a legal representative;

Exclusion Criteria:

• Patents with cognitive dysfunction preoperatively;

• Patents with verbal, visual and auditory defects;

• Patients with history of alcohol and/or drug abuse, or history of neurological and psychotic disorders;

• Patients with history of hospital admission and therapy within 30 days.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction

Locations

Country	Name	City	State
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (17)

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* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	relative level of LINC01844	The relative level of LINC01844 in peripheral blood is measured by qRT-PCR according to the instructions from the SYBR Green PCR Master Mix Kit (Qiagen).	preoperative day and postoperative day 1,3 and 5
Secondary	serum reactive protein-C	Serum reactive protein-C is measured by an ELISA kit	preoperative day and postoperative day 1,3 and 5
Secondary	serum interleukin-6	Serum interleukin-6 is measured by an ELISA kit	preoperative day and postoperative day 1,3 and 5