Does Sevoflurane Cause Genomic Damage
Primary Purpose
Anesthesia; Adverse Effect
Status
Unknown status
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Sevoflurane
Propofol
Sponsored by
About this trial
This is an interventional supportive care trial for Anesthesia; Adverse Effect focused on measuring genomic instability, Sevoflurane, General anaesthesia
Eligibility Criteria
Inclusion Criteria
- Children must have isolated cleft lip or palate.
- The surgery must be a primary repair of cleft lip or palate.
- The minimum duration of the surgery must be 90 minutes.
Exclusion Criteria
- Children who have undergone previous surgery.
- Children who have syndromic cleft lip or palate.
- Children with bleeding disorders.
- Children with known allergy to any of the concerned drugs.
Sites / Locations
- Jubilee Mission Medical College and Research InstituteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Group S
Group P
Arm Description
These patients will be induced and maintained with sevoflurane during anaesthesia.
These patients will be induced and maintained with propofol during anaesthesia.
Outcomes
Primary Outcome Measures
Genomic instability
Genomic instability will be assessed using comet assay
Genomic instability
Genomic instability will be assessed using comet assay.
Secondary Outcome Measures
Reversibility of the genomic instability
Assessed using comet assay
Reversibility of genomic instability
It will be assessed using comet assay.
Full Information
NCT ID
NCT03109119
First Posted
March 20, 2017
Last Updated
January 11, 2019
Sponsor
Jubilee Mission Medical College and Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT03109119
Brief Title
Does Sevoflurane Cause Genomic Damage
Official Title
Does Sevoflurane Induce Genomic Instability in Patients Undergoing General Anaesthesia?
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
September 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jubilee Mission Medical College and Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to find out if sevoflurane causes any cell damage to patients undergoing general anaesthesia. In case of any damage, the reversibility of the damage is also assessed. This is a prospective, comparative study carried out in all children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery under Smile Train organisation ìn our hospital,who satisfy the inclusion and exclusion criteria.
Detailed Description
STUDY GOALS AND OBJECTIVES
To find out if sevoflurane induces genomic instability in children undergoing cleft lip and palate repair.
To assess the magnitude of genomic damage caused by the sevoflurane anaesthesia.
To evaluate the reversibility of the induced genomic instability when exposure is discontinued.
STUDY DESIGN Type of study : Prospective Comparative Study Research population : All children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery of our hospital, who satisfy the inclusion and exclusion criteria.
Sample Size : A total of 30 children will be enrolled for the study. METHODOLOGY Children scheduled to undergo surgical repair of cleft lip or palate were enrolled for the study, after addressing the inclusion and exclusion criteria.
A peripheral blood sample of 1.5 ml (S-1) will be taken before the induction of anaesthesia .All children will be randomly allocated into two groups - group S and P.All children will be premedicated with Inj.Glycopyrolate 0.01 mg/kg . Children in group S will be induced with sevoflurane, whereas children in group P will be induced with propofol.All children will be intubated using I / V Vecuronium 0.1 mg / kg .Analgesia will be provided using I / V Fentanyl 1.5 mcg / kg. Depth of anaesthesia will be maintained with sevoflurane in group S and with propofol infusion in group P. The vitals will be monitored as usual intraop and the children will be extubated at the end of the surgery.
Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day All the blood samples will be evaluated for genomic instability using Alkaline Comet Assay by the Genetics Lab of our hospital.
STATISTICAL ANALYSIS
The findings of this study will be analysed using Chi-square test, Student's t-test, Mann-Whitney U test, mean and standard deviation to yield the final results. The study will be considered statistically significant with a p value of less than 0.05
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anesthesia; Adverse Effect
Keywords
genomic instability, Sevoflurane, General anaesthesia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
All children will be randomly allocated into two groups - group S and P. Children in group S will be anaesthetised with sevoflurane, whereas children in group P will be anaesthetised with propofol.
Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day.
These blood samples will be evaluated for genomic instability using Alkaline Comet Assay and micronucleus test by the Genetics Lab of our hospital.
Masking
ParticipantOutcomes Assessor
Masking Description
This is a double blinded study, where the participants are randomly selected using a computer - generated number and allocated to any one of the two groups. Both the patient and the outcome assessor will be blinded.
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group S
Arm Type
Active Comparator
Arm Description
These patients will be induced and maintained with sevoflurane during anaesthesia.
Arm Title
Group P
Arm Type
Sham Comparator
Arm Description
These patients will be induced and maintained with propofol during anaesthesia.
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Other Intervention Name(s)
sevorane
Intervention Description
The patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia.
Intervention Type
Drug
Intervention Name(s)
Propofol
Other Intervention Name(s)
fresofol
Intervention Description
These patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion.
Primary Outcome Measure Information:
Title
Genomic instability
Description
Genomic instability will be assessed using comet assay
Time Frame
It will be assessed at 2 hours after anaesthesia.
Title
Genomic instability
Description
Genomic instability will be assessed using comet assay.
Time Frame
It will be assessed 48 hours after anaesthesia.
Secondary Outcome Measure Information:
Title
Reversibility of the genomic instability
Description
Assessed using comet assay
Time Frame
It will be assessed on fifth day after anaesthesia.
Title
Reversibility of genomic instability
Description
It will be assessed using comet assay.
Time Frame
It will be assessed on the 14th day after anaesthesia.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Children must have isolated cleft lip or palate.
The surgery must be a primary repair of cleft lip or palate.
The minimum duration of the surgery must be 90 minutes.
Exclusion Criteria
Children who have undergone previous surgery.
Children who have syndromic cleft lip or palate.
Children with bleeding disorders.
Children with known allergy to any of the concerned drugs.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vigil Peter, MD
Phone
918593821000
Email
drpeteralapatt@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Alex George, PhD
Phone
914872432200
Email
alexgeorge@jmmc.ac.in
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vigil Peter, MD
Organizational Affiliation
Jubilee Mission Medical College and Research Institute, Thrissur, India
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jubilee Mission Medical College and Research Institute
City
Thrissur
State/Province
Kerala
ZIP/Postal Code
680005
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vigil Peter, MD
Phone
918593821000
Email
drpeteralapatt@gmail.com
First Name & Middle Initial & Last Name & Degree
Alex George, PhD
Phone
914872432200
Email
alexgeorge@jmmc.ac.in
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
15306730
Citation
Szyfter K, Szulc R, Mikstacki A, Stachecki I, Rydzanicz M, Jaloszynski P. Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet. 2004;45(3):369-74.
Results Reference
result
PubMed Identifier
23525098
Citation
Musak L, Smerhovsky Z, Halasova E, Osina O, Letkova L, Vodickova L, Polakova V, Buchancova J, Hemminki K, Vodicka P. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand J Work Environ Health. 2013 Nov;39(6):618-30. doi: 10.5271/sjweh.3358. Epub 2013 Mar 22.
Results Reference
result
PubMed Identifier
10517999
Citation
Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res. 1999 Jul 16;428(1-2):271-83. doi: 10.1016/s1383-5742(99)00053-8.
Results Reference
result
PubMed Identifier
18540930
Citation
Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M. Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia. 2008 Aug;63(8):861-4. doi: 10.1111/j.1365-2044.2008.05498.x. Epub 2008 Jun 6.
Results Reference
result
Citation
Tania K.de Araujo, Roseane L, Flora M.B.B, Nilson C.R, Cristina W.P, Ricardo Manoel da Cruz et al-Genotoxic effects of anaesthetics in OT personnel evaluated by micronuclei tests Journal of Anaesthesia and Clinical Science ISSN 2049-9752,10.7243/2049-9752-2-26,2013
Results Reference
result
PubMed Identifier
18023252
Citation
Rozgaj R, Kasuba V, Brozovic G, Jazbec A. Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test. Int J Hyg Environ Health. 2009 Jan;212(1):11-7. doi: 10.1016/j.ijheh.2007.09.001. Epub 2007 Nov 26.
Results Reference
result
PubMed Identifier
25386035
Citation
Alcaraz M, Quesada S, Armero D, Martin-Gil R, Olivares A, Achel GD. Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation. Colomb Med (Cali). 2014 Sep 30;45(3):104-9. eCollection 2014 Jul-Sep.
Results Reference
result
PubMed Identifier
21944903
Citation
Braz MG, Braz LG, Barbosa BS, Giacobino J, Orosz JE, Salvadori DM, Braz JR. DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia. Mutat Res. 2011 Dec 24;726(2):251-4. doi: 10.1016/j.mrgentox.2011.09.007. Epub 2011 Sep 16.
Results Reference
result
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Does Sevoflurane Cause Genomic Damage
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