Anesthetic Methods and Gene Expression Profile

Hip Arthroplasty Clinical Trial

— GeSTA  

Official title:

Effect of Anesthetics Used for Regional vs General vs Integrated Anesthesia on the Modulation of 'Stress-responsive' Genes Involved in the Metabolism and Cellular Detoxification

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03585647
• Other study ID #: 12630
• Status: Completed
• Start date: September 15, 2014
• Est. completion date: November 30, 2016

Study information

• Verified date: April 2019
• Source: University of Bologna
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study will analyze differentially regulated genes involved in oxidative stress and toxicology in peripheral blood mononuclear cells (PBMCs) of patients who underwent arthroplasty under three different anesthetic methods. The investigator hypothesized that anesthesia procedures trigger toxicity, thus inducing changes in the messenger ribonucleic acid (mRNA) profile. The results may provide a more profound understanding of the molecular mechanism of anesthesia and in overcoming the adverse effects arising from their use.

Description:

By using a computer-generated randomization table, hospitalized patients undergoing elective hip arthroplasty will be randomly consecutively allocated to receive general (GA group), regional (RA group), or integrated (IA group) anesthesia. Patients with contraindication to spinal anesthesia or lumbar catheter placement, as well as obese patients, with arterial hypertension not controlled by oral medication, severe pulmonary, cardiovascular, renal, hepatic, cerebrovascular, or psychiatric diseases will be excluded from the study.

Whole blood samples (10 mL) will be obtained from all enrolled patients at three time points:

early morning on the operation day (T0), after surgery (T1) and third day (T2) after surgery. The samples will be collected in heparin tubes and PBMCs will be isolated and used for gene expression analysis. Serum obtained after blood centrifugation will be used for hematological and biochemical analysis such as glutamate oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), bilirubin (BIL), creatinine (CREA), creatine phosphokinase (CPK), hemoglobin (HB).

The sample size was determined according to Lee- Whitmore * and G*Power Ftest for ANOVA Fixed effects, omnibus, one-way (Lee ML, Whitmore GA. Stat Med. 2002;21: 3543-3570). Assuming a Poisson distribution for the expected value of the false-positive gene expression of the 9 chosen genes and fixing at 1 the maximum expected value for false positives E(R0) and considering all the 84 genes as not differentially expressed (G0=G=9), the probability α for any single gene among the G genes that are not differentially expressed is given by α=E(R_0 )/G=1/9=0.011, with the Bonferroni correction it becomes α_c=(0.011)/3=0.037. This is the type I error of a false positive expression. Moreover, considering as primary endpoint the fold increase of the gene expression, assuming a log-normal distribution with standard deviation of 0.7 which is typical of moderate-high gene expression and therefore a conservative one for the sample size determination and imposing a minimum difference on logarithmic scale among the 3 groups of 0.5 with a power of at least 0.8 and a Bonferroni corrected type I error α=0.05/3=0.0167 (which is smaller and then conservative, than the previous α_c) the minimum sample size(G*POWER)^ for each group is 30 patients, by considering a 10% of drop-out , the chosen sample size was 33 patients per group which leads to a total sample size of 99 patients.

^F tests - ANOVA: Fixed effects, omnibus, one-way Analysis: A priori: Compute required sample size Input: Effect size f = 0.7 α err prob = 0.0167 Power (1-β err prob) = 0.8 Number of groups = 3 Output: Noncentrality parameter λ = 14.7000000 Critical F = 4.7803455 Numerator df = 2 Denominator df = 27 Total sample size = 30 Actual power = 0.8009945

The normal distribution of continuous variables will be evaluated by Kolmogorov-Smirnov test. The Chi-square test will be used to evaluate categorical variables. The differences between groups will be evaluated by means of parametric ANOVA tests followed by Tukey test. Multiple regression analysis will be performed to evaluate the influence of biochemical parameters on gene expression in response to anesthetics considering confounding factors such as age, gender, BMI, smoking. Values of p <0.05 will be considered statistically significant. All tests will be performed using software (SPSS, Chicago, USA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: November 30, 2016
• Est. primary completion date: June 20, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists Classification (ASA Class) = I-II.

Exclusion Criteria:

• American Society of Anesthesiologists Classification (ASA Class) > III

• contraindication to spinal anaesthesia or lumbar catheter placement

• arterial hypertension not controlled by oral medication

• severe pulmonary

• cardiovascular disease

• renal disease

• hepatic disease

• cerebrovascular disease

• psychiatric diseases

Related Conditions & MeSH terms

• Hip Arthroplasty

Intervention

Procedure:
• hip arthroplasty
Hip replacement is a surgery for people with severe hip damage. The most common cause of damage is osteoarthritis.

Locations

Country	Name	City	State
Italy	Rizzoli Orthopaedic Institute	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
University of Bologna

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Alleva R, Tomasetti M, Solenghi MD, Stagni F, Gamberini F, Bassi A, Fornasari PM, Fanelli G, Borghi B. Lymphocyte DNA damage precedes DNA repair or cell death after orthopaedic surgery under general anaesthesia. Mutagenesis. 2003 Sep;18(5):423-8. — View Citation

Borghi B, Casati A, Iuorio S, Celleno D, Michael M, Serafini PL, Alleva R. Effect of different anesthesia techniques on red blood cell endogenous recovery in hip arthroplasty. J Clin Anesth. 2005 Mar;17(2):96-101. — View Citation

Ishikawa M, Tanaka S, Arai M, Genda Y, Sakamoto A. Differences in microRNA changes of healthy rat liver between sevoflurane and propofol anesthesia. Anesthesiology. 2012 Dec;117(6):1245-52. doi: 10.1097/ALN.0b013e3182746676. — View Citation

Nakazato K, Yoshida Y, Takemori K, Kobayashi K, Sakamoto A. Expressions of genes encoding drug-metabolizing enzymes are altered after sevoflurane, isoflurane, propofol or dexmedetomidine anesthesia. Biomed Res. 2009 Feb;30(1):17-24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of Gene expression profile from baseline at time points	Effect of anesthesia techniques on the expression of genes indicative of stress and toxicity	Gene expression will be evaluated in PBMCs at baseline (T0), up-30 min after surgery (T1) and on the third day (T2) after surgery.
Secondary	Relationship between deregulated genes and hepatic/renal cytotoxicity from baseline at time points	Multiple regression analysis of deregulated gene expression values (relative expression) and HB (mg/ml), hepatic markers such as GOT, GPT, BIL (mg/dl), and renal markers including CREA and CPK (mg/dl) will been performed. The results will be reported as coefficient of regression (r) with statistical significance p<0.05.	Biochemical analysis have been evaluated in blood collected at baseline (T0), up-30 min after surgery (T1) and on the third day (T2) after surgery.