Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06387836
Status:
RECRUITING
Last Update Posted:
2024-04-29
First Post:
2024-04-23
Brief Title:
LINC01844 as a Diagnostic Biomarker for POCD in Elderly Patients
Sponsor:
Shanghai Zhongshan Hospital
Organization:
Shanghai Zhongshan Hospital
Study Overview
Official Title:
Clinical Study on LINC01844 as a Diagnostic Marker for Early Postoperative Cognitive Dysfunction in Elderly Patients
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 RNALINC01844 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
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
Detailed 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 8Lmin General anesthesia is induced with sufentanil 02ugkg propofol target controlled infusion TCI at plasma concentration of 3ugml remifentanilTCI at plasma concentration of 3 ngml and rocuronium 06mgkg 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 06mg 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 12000 g 4C for 15 min then the aqueous phase containing the RNA is transferred to a new tube and isopropanol 05 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 260280 180 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 95C for 10 min 45 cycles at 95C for 15 s 60C for 30s and 72C 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 1961 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 http10157137 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 recruitmentretention 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 05 Based on results from preliminary trial the AUC was 073 and the incidence of POCD was 333 Sample size was calculated by PASS version 110 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 andor 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
Anesthesia After the patients entered the operating room the vital signs are monitored the patients are given oxygen inhalation 8Lmin General anesthesia is induced with sufentanil 02ugkg propofol target controlled infusion TCI at plasma concentration of 3ugml remifentanilTCI at plasma concentration of 3 ngml and rocuronium 06mgkg 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 06mg 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 12000 g 4C for 15 min then the aqueous phase containing the RNA is transferred to a new tube and isopropanol 05 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 260280 180 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 95C for 10 min 45 cycles at 95C for 15 s 60C for 30s and 72C 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 1961 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 http10157137 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 recruitmentretention 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 05 Based on results from preliminary trial the AUC was 073 and the incidence of POCD was 333 Sample size was calculated by PASS version 110 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None