Oxidative Stress InductionNCT05857202
Oxidative Stress and Inflammation Biomarkers in Surgically Treated Patients With Laryngeal Cancer
An observational study of Oxidative Stress Induction and Laryngeal Cancer, run by Clinical Centre of Serbia at 2 sites in Serbia.
Trial summary
A experimental interventional prospective study will include patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. Clinical and demographic characteristics of the patients would be noted. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Oxidative Stress Induction, Laryngeal Cancer, Interleukins
- What is being tested?
- Analgesics, Opioid and Analgesics, Non-Narcotic
- How many people
- 100 participants
- Where
- 2 sitesSerbia
- Study dates
- 1 Sep 2022to 30 Oct 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study would include 100 patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination, laryngomicroscopic examination with the biopsy and histopathologic examination. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease. The modality of surgical treatment was decided on the institutional Oncological Board and involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy.
Who may be able to join
- patients with all stages of diagnosed and operable laryngeal squamocellular carcinoma (T1-T4, N0-N2)
Who cannot join
- inoperable malignant disease
- presence of distant metastases
- previously treated malignancies
- presence of neurological or other severe comorbidities which prevent surgical treatment
- the presence of neurological or other severe physical and metabolic comorbidities
- substance abuse
- the inability to provide informed consent.
Trial locations and contacts
2 sites in 1 country.
Serbia2 sites, 2 recruiting
- Recruiting
Clinic for otorhinolaryngology and maxillofacial surgery, Clinical Center of Serbia
Belgrade, 11000
Ana D Jotic, MD, PhD, +381637789825, anajotic@yahoo.com
- Recruiting
Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
Belgrade, 11000
Katarina R Savic Vujovic, MD, PhD, +381 63 776 3960, katarinasavicvujovic@gmail.com
Andjela T Zivkovic, MD
About this study
Official title: Oxidative Stress and Inflammation Biomarkers in Correlation to Postoperative Pain Modulation in Surgically Treated Patients With Laryngeal Cancer
A experimental interventional prospective study will include patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. Clinical and demographic characteristics of the patients would be noted. The visual analog scale (VAS), Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for pain assessment. Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma. The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder. Blood samples ware taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined.
The aim of the study will be to assess concentrations of inflammatory biomarkers (IL-1, IL-6) and oxidative stress factors (MDA, SOD, GPKS1) in postoperative course in surgically treated patients with laryngeal carcinoma and in possible complication occurrence. Also, their correlation to type and dosage of used analgesics, to pain assessment questionnaire scores and QOL questionnaire scores in surgically treated patients with laryngeal carcinoma will be assessed.
Read the detailed description
Patient selection
A experimental interventional prospective study would include 100 patients with squamocellular carcinoma of the larynx surgically treated in the period from October 2022 to February 2023 at the tertiary referral center. This study was approved by the Institutional Ethics Committee (745/5-22), and all patients signed the informed consent form prior to their inclusion in the study. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination and laryngomicroscopic examination of the larynx with the biopsy and histopathologic examination of the tissue. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease. Study included patients with all stages of operable laryngeal carcinoma (T1-T4, N0-N2), without previous treated malignancies. Exclusion criteria were inoperable malignant disease, presence of distant metastases, previously treated malignancies, presence of neurological or other severe comorbidities which prevent surgical treatment, the presence of neurological or other severe physical and metabolic comorbidities, substance abuse, and the inability to provide informed consent.
The modality of treatment for every patient was decided on the institutional Oncological Board (consisting of a radiotherapist, head and neck surgeons, an oncologist, and a histopathologist). Open surgical treatment involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy. Demographic, clinical and histopathological characteristics (age and gender, tobacco use, histopathological tumor grade, TNM classification, and therapy modality) were noted.
Quality of life assessment
Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma.
Pain assessment
The visual analog scale (VAS) was used for pain assessment. Scores were based on self-reported measures of pain severety that are recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 cm on the left end of the scale marks ''no pain'' and 10 cm on the right end of the scale marks ''the worst pain'').
Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for quality assessment of postoperative pain
Postoperative analgesia
The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder: (1) for mild to moderate pain, a non-opioid (acetaminophen or non-steroid anti-inflammatory drug , NSAID) with or without an adjuvant; (2) for moderate or severe pain, a non-opioid with an opioid for moderate pain and (3) an opioid for moderate to severe pain not combined with another agent.
Measurement of the Oxidative Stress and Inflammatory Parameters
Blood was taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined by coated enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer's instructions (Elabscience, Wuhan, China). The ELISA kits for determination of concentrations of IL-1 and IL-6 were based on the Sandwich ELISA principle, with plates pre-coated with an antibody specific to human cytokines. The optical density (OD) was measured spectrophotometrically at 450 nm, using a Multiskan EX plate reader (Thermo Fisher Scientific, Vantaa, Finland). The concentration of analytesin of the tested samples was calculated by comparing the OD of the samples to the standard curve created with GraphPad Prism 9.0 software (GraphPad Software Inc., San Diego, CA, USA).
Statistical analysis
Categorical data was described by absolute and relative numbers (in percentages), while numerical data was reported as arithmetic mean and standard deviation or median and interquartile range (IQR), depending on the data distribution. The normality was evaluated using mathematical (Shapiro-Willk, skewness and kurtosis, and coefficient of variation) and graphical (histogram, box plot) methods. For the evaluation of changing of pain intensity, parameters of oxidative stress, and biomarkers of inflammation Friedman test was applied with Wilcoxon signed rank test as post-hoc testing method. For analyzing the association between pain intensity (VAS), parameters of oxidative stress, and biomarkers of inflammation Spearman's rank correlation coefficient was used, because variables didn't have normal distribution. In order to evaluate all possible factors that influence the level of oxidative stress expressed as SOD and MDA levels, linear regression analysis (enter method) was performed reporting regression coefficient B, 95% confidence level (CI) of B, and p value. Univariate analysis was done first, and all significant factors were combined in multivariate models. All statistical methods were considered significant if p value was less or equal 0.05. The analysis was performed in IBM SPSS ver. 26.
- Conditions
- Oxidative Stress Induction, Laryngeal Cancer, Interleukins, Pain Management, Quality of Life, Pain, Postoperative
- Being tested
- Analgesics, Opioid, Analgesics, Non-Narcotic
- Keywords
- oxidative stress, laryngeal cancer, pain management, interleukins
- Medical subject headings
- Laryngeal Neoplasms, Agnosia, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analgesics, OpioidDrug
Drugs were given immediately after the surgery, and correlation between analgesic use and parameters of oxidative stress and inflammation was assessed.
Analgesics, Non-NarcoticDrug
Drugs were given immediately after the surgery, and correlation between analgesic use and parameters of oxidative stress and inflammation was assessed.
| Study group | Role | What they receive |
|---|---|---|
| Operated laryngeal cancer patients treated with non narcotic | Operated laryngeal cancer patients who were administered non narcotic drugs postoperative for pain management Receives: Drug: Analgesics, Non-Narcotic | |
| Operated laryngeal cancer patients treated with non narcotic and opioids | Operated laryngeal cancer patients who were administered non narcotic and opioids postoperative for pain management Receives: Drug: Analgesics, Opioid; Drug: Analgesics, Non-Narcotic | |
| Operated laryngeal cancer patients treated with opioids | Operated laryngeal cancer patients who were administered opioids postoperative for pain management Receives: Drug: Analgesics, Opioid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between inflammatory marker IL-1 and pain intensity
A positive correlation between concentration of inflammatory marker IL-1 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected.
The concentrations of inflammatory parameters IL-1 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions.
Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain'').
Correlation would be calculated with Spearman's rank correlation coefficient.
Measured: 7 days
Correlation between inflammatory marker IL-6 and pain intensity
A positive correlation between concentration of inflammatory marker IL-6 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected.
The concentrations of inflammatory marker IL-6 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions.
Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain'').
Correlation would be calculated with Spearman's rank correlation coefficient.
Measured: 7 days
Correlation between inflammatory marker CRP and pain intensity
A positive correlation between concentration of inflammatory marker CRP and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected.
The concentrations of inflammatory marker CRP (ng/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions.
Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain'').
Correlation would be calculated with Spearman's rank correlation coefficient.
Measured: 7 days
Correlation between oxidative stress marker MDA and pain intensity
A positive correlation between concentration of oxidative stress marker MDA and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected.
The concentrations of oxidative stress marker MDA (ng/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions.
Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain'').
Correlation would be calculated with Spearman's rank correlation coefficient.
Measured: 7 days
Correlation between anti- oxidative stress marker SOD and pain intensity
A negative correlation between concentration of anti-oxidative stress marker SOD and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected.
The concentrations of anti-oxidative stress marker SOD (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions.
Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain'').
Correlation would be calculated with Spearman's rank correlation coefficient.
Measured: 7 days
Correlation between anti- oxidative stress marker GPX1 and pain intensity
A negative correlation between concentration of anti- oxidative stress marker GPX1 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected.
The concentrations of anti-oxidative stress marker GPX1 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions.
Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain'').
Correlation would be calculated with Spearman's rank correlation coefficient.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2023
- Study start1 Sep 2022
- Primary completion1 Sep 2023 (estimated)
- Study completion30 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Oxidative Stress InductionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Centre of Serbia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Belgrade
- Responsible party
- Principal investigator, Ana Jotić, Clinical Centre of Serbia
- Investigators
- Ana D Jotic, MD, PhD, Study director, Clinic for otorhinolaryngology and maxillofacial surgery, Clinical center of SerbiaKatarina R Savic Vujovic, MD, PhD, Study director, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05857202
- Sponsor's protocol ID
- 754/5
- Status last verified
- May 2023
- First submitted
- 29 Mar 2023
- Last updated
- 12 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Available and ethical compliant patients data will be submitted to the data repository
Publications
Hinther A, Nakoneshny SC, Chandarana SP, Wayne Matthews T, Dort JC. Efficacy of postoperative pain management in head and neck cancer patients. J Otolaryngol Head Neck Surg. 2018 May 2;47(1):29. doi: 10.1186/s40463-018-0274-y.
PubMed 29720267Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem. 2017 Jun 20;86:715-748. doi: 10.1146/annurev-biochem-061516-045037. Epub 2017 Apr 24.
PubMed 28441057Niklander SE, Murdoch C, Hunter KD. IL-1/IL-1R Signaling in Head and Neck Cancer. Front Oral Health. 2021 Aug 26;2:722676. doi: 10.3389/froh.2021.722676. eCollection 2021.
PubMed 35048046Purdy M, Karkkainen J, Kokki M, Anttila M, Aspinen S, Juvonen P, Kokki H, Pulkki K, Rantanen T, Eskelinen M. Does Rectus Sheath Block Analgesia Alter Levels of the Oxidative Stress Biomarker Glutathione Peroxidase: A Randomised Trial of Patients with Cancer and Benign Disease. Anticancer Res. 2017 Feb;37(2):897-902. doi: 10.21873/anticanres.11396.
PubMed 28179349Salzman R, Kankova K, Pacal L, Tomandl J, Horakova Z, Kostrica R. Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases. Neoplasma. 2007;54(4):321-5.
PubMed 17822322Uz U, Eskiizmir G. Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review. Clin Exp Otorhinolaryngol. 2021 Feb;14(1):50-60. doi: 10.21053/ceo.2019.00906. Epub 2021 Feb 1.
PubMed 33587847Rettig TC, Verwijmeren L, Dijkstra IM, Boerma D, van de Garde EM, Noordzij PG. Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery. Ann Surg. 2016 Jun;263(6):1207-12. doi: 10.1097/SLA.0000000000001342.
PubMed 26135695Karkkainen J, Selander T, Purdy M, Juvonen P, Eskelinen M. Patients with Increased Levels of the Oxidative Stress Biomarker SOD1 Appear to Have Diminished Postoperative Pain After Midline Laparotomy: A Randomised Trial with Special Reference to Postoperative Pain Score (NRS). Anticancer Res. 2018 Feb;38(2):1003-1008. doi: 10.21873/anticanres.12315.
PubMed 29374733Liu Q, Xu K. Evaluation of some cellular biomarker proteins, oxidative stress and clinical indices as results of laparoscopic appendectomy for perforated appendicitis in children. Cell Mol Biol (Noisy-le-grand). 2020 Jun 5;66(3):197-203.
PubMed 32538771Si HB, Yang TM, Zeng Y, Zhou ZK, Pei FX, Lu YR, Cheng JQ, Shen B. Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty. BMC Musculoskelet Disord. 2017 Jun 17;18(1):265. doi: 10.1186/s12891-017-1597-y.
PubMed 28623906Xi MY, Li SS, Zhang C, Zhang L, Wang T, Yu C. Nalbuphine for Analgesia After Orthognathic Surgery and Its Effect on Postoperative Inflammatory and Oxidative Stress: A Randomized Double-Blind Controlled Trial. J Oral Maxillofac Surg. 2020 Apr;78(4):528-537. doi: 10.1016/j.joms.2019.10.017. Epub 2019 Nov 5.
PubMed 31785250Liu D, Liu H, Wu J, Gong B. Effects of Thoracic Paravertebral Blockon Inflammatory Response, Stress Response, Hemodynamics and Anesthesia Resuscitation inGallbladder Carcinoma. Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):171-177. doi: 10.14715/cmb/2022.68.2.24.
PubMed 35869710Zivkovic A, Jotic A, Dozic I, Randjelovic S, Cirkovic I, Medic B, Milovanovic J, Trivic A, Korugic A, Vukasinovic I, Savic Vujovic K. Role of Oxidative Stress and Inflammation in Postoperative Complications and Quality of Life After Laryngeal Cancer Surgery. Cells. 2024 Nov 23;13(23):1951. doi: 10.3390/cells13231951.
PubMed 39682700
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Stress and Inflammation Biomarkers in Correlation to Postoperative Pain Modulation in Surgically Treated Patients With Laryngeal Cancer
- ClinicalTrials.gov ID
- NCT05857202
- Acronym / sponsor ID
- 754/5
- Conditions
- Oxidative Stress Induction, Laryngeal Cancer, Interleukins, Pain Management, Quality of Life, Pain, Postoperative
- Keywords
- oxidative stress, laryngeal cancer, pain management, interleukins
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Clinical Centre of SerbiaUniversity, hospital or other
- Collaborators
- University of Belgrade
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 30 Oct 2023 (estimated)
- First posted
- 12 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A experimental interventional prospective study will include patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. Clinical and demographic characteristics of the patients would be noted. The visual analog scale (VAS), Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for pain assessment. Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma. The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder. Blood samples ware taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined.
The aim of the study will be to assess concentrations of inflammatory biomarkers (IL-1, IL-6) and oxidative stress factors (MDA, SOD, GPKS1) in postoperative course in surgically treated patients with laryngeal carcinoma and in possible complication occurrence. Also, their correlation to type and dosage of used analgesics, to pain assessment questionnaire scores and QOL questionnaire scores in surgically treated patients with laryngeal carcinoma will be assessed.
Detailed description
Patient selection
A experimental interventional prospective study would include 100 patients with squamocellular carcinoma of the larynx surgically treated in the period from October 2022 to February 2023 at the tertiary referral center. This study was approved by the Institutional Ethics Committee (745/5-22), and all patients signed the informed consent form prior to their inclusion in the study. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination and laryngomicroscopic examination of the larynx with the biopsy and histopathologic examination of the tissue. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease. Study included patients with all stages of operable laryngeal carcinoma (T1-T4, N0-N2), without previous treated malignancies. Exclusion criteria were inoperable malignant disease, presence of distant metastases, previously treated malignancies, presence of neurological or other severe comorbidities which prevent surgical treatment, the presence of neurological or other severe physical and metabolic comorbidities, substance abuse, and the inability to provide informed consent.
The modality of treatment for every patient was decided on the institutional Oncological Board (consisting of a radiotherapist, head and neck surgeons, an oncologist, and a histopathologist). Open surgical treatment involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy. Demographic, clinical and histopathological characteristics (age and gender, tobacco use, histopathological tumor grade, TNM classification, and therapy modality) were noted.
Quality of life assessment
Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma.
Pain assessment
The visual analog scale (VAS) was used for pain assessment. Scores were based on self-reported measures of pain severety that are recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 cm on the left end of the scale marks ''no pain'' and 10 cm on the right end of the scale marks ''the worst pain'').
Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for quality assessment of postoperative pain
Postoperative analgesia
The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder: (1) for mild to moderate pain, a non-opioid (acetaminophen or non-steroid anti-inflammatory drug , NSAID) with or without an adjuvant; (2) for moderate or severe pain, a non-opioid with an opioid for moderate pain and (3) an opioid for moderate to severe pain not combined with another agent.
Measurement of the Oxidative Stress and Inflammatory Parameters
Blood was taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined by coated enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer's instructions (Elabscience, Wuhan, China). The ELISA kits for determination of concentrations of IL-1 and IL-6 were based on the Sandwich ELISA principle, with plates pre-coated with an antibody specific to human cytokines. The optical density (OD) was measured spectrophotometrically at 450 nm, using a Multiskan EX plate reader (Thermo Fisher Scientific, Vantaa, Finland). The concentration of analytesin of the tested samples was calculated by comparing the OD of the samples to the standard curve created with GraphPad Prism 9.0 software (GraphPad Software Inc., San Diego, CA, USA).
Statistical analysis
Categorical data was described by absolute and relative numbers (in percentages), while numerical data was reported as arithmetic mean and standard deviation or median and interquartile range (IQR), depending on the data distribution. The normality was evaluated using mathematical (Shapiro-Willk, skewness and kurtosis, and coefficient of variation) and graphical (histogram, box plot) methods. For the evaluation of changing of pain intensity, parameters of oxidative stress, and biomarkers of inflammation Friedman test was applied with Wilcoxon signed rank test as post-hoc testing method. For analyzing the association between pain intensity (VAS), parameters of oxidative stress, and biomarkers of inflammation Spearman's rank correlation coefficient was used, because variables didn't have normal distribution. In order to evaluate all possible factors that influence the level of oxidative stress expressed as SOD and MDA levels, linear regression analysis (enter method) was performed reporting regression coefficient B, 95% confidence level (CI) of B, and p value. Univariate analysis was done first, and all significant factors were combined in multivariate models. All statistical methods were considered significant if p value was less or equal 0.05. The analysis was performed in IBM SPSS ver. 26.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Operated laryngeal cancer patients treated with non narcotic | – | Drug: Analgesics, Non-NarcoticOperated laryngeal cancer patients who were administered non narcotic drugs postoperative for pain management |
| Operated laryngeal cancer patients treated with non narcotic and opioids | – | Drug: Analgesics, Opioid, Drug: Analgesics, Non-NarcoticOperated laryngeal cancer patients who were administered non narcotic and opioids postoperative for pain management |
| Operated laryngeal cancer patients treated with opioids | – | Drug: Analgesics, OpioidOperated laryngeal cancer patients who were administered opioids postoperative for pain management |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study would include 100 patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination, laryngomicroscopic examination with the biopsy and histopathologic examination. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease. The modality of surgical treatment was decided on the institutional Oncological Board and involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy.
Key inclusion criteria (1 listed)
- patients with all stages of diagnosed and operable laryngeal squamocellular carcinoma (T1-T4, N0-N2)
Key exclusion criteria (7 listed)
- inoperable malignant disease
- presence of distant metastases
- previously treated malignancies
- presence of neurological or other severe comorbidities which prevent surgical treatment
- the presence of neurological or other severe physical and metabolic comorbidities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analgesics, OpioidDrugs were given immediately after the surgery, and correlation between analgesic use and parameters of oxidative stress and inflammation was assessed. | Drug | Operated laryngeal cancer patients treated with non narcotic and opioids, Operated laryngeal cancer patients treated with opioids |
| Analgesics, Non-NarcoticDrugs were given immediately after the surgery, and correlation between analgesic use and parameters of oxidative stress and inflammation was assessed. | Drug | Operated laryngeal cancer patients treated with non narcotic, Operated laryngeal cancer patients treated with non narcotic and opioids |
Primary outcome
Correlation between inflammatory marker IL-1 and pain intensity
Time frame: 7 days
A positive correlation between concentration of inflammatory marker IL-1 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of inflammatory parameters IL-1 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.
Correlation between inflammatory marker IL-6 and pain intensity
Time frame: 7 days
A positive correlation between concentration of inflammatory marker IL-6 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of inflammatory marker IL-6 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.
Correlation between inflammatory marker CRP and pain intensity
Time frame: 7 days
A positive correlation between concentration of inflammatory marker CRP and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of inflammatory marker CRP (ng/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.
Correlation between oxidative stress marker MDA and pain intensity
Time frame: 7 days
A positive correlation between concentration of oxidative stress marker MDA and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of oxidative stress marker MDA (ng/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.
Correlation between anti- oxidative stress marker SOD and pain intensity
Time frame: 7 days
A negative correlation between concentration of anti-oxidative stress marker SOD and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of anti-oxidative stress marker SOD (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.
Correlation between anti- oxidative stress marker GPX1 and pain intensity
Time frame: 7 days
A negative correlation between concentration of anti- oxidative stress marker GPX1 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of anti-oxidative stress marker GPX1 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2023.
- Background: PubMed 29720267Hinther A, Nakoneshny SC, Chandarana SP, Wayne Matthews T, Dort JC. Efficacy of postoperative pain management in head and neck cancer patients. J Otolaryngol Head Neck Surg. 2018 May 2;47(1):29. doi: 10.1186/s40463-018-0274-y.
- Background: PubMed 28441057Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem. 2017 Jun 20;86:715-748. doi: 10.1146/annurev-biochem-061516-045037. Epub 2017 Apr 24.
- Background: PubMed 35048046Niklander SE, Murdoch C, Hunter KD. IL-1/IL-1R Signaling in Head and Neck Cancer. Front Oral Health. 2021 Aug 26;2:722676. doi: 10.3389/froh.2021.722676. eCollection 2021.
- Results publication: PubMed 28179349Purdy M, Karkkainen J, Kokki M, Anttila M, Aspinen S, Juvonen P, Kokki H, Pulkki K, Rantanen T, Eskelinen M. Does Rectus Sheath Block Analgesia Alter Levels of the Oxidative Stress Biomarker Glutathione Peroxidase: A Randomised Trial of Patients with Cancer and Benign Disease. Anticancer Res. 2017 Feb;37(2):897-902. doi: 10.21873/anticanres.11396.
- Results publication: PubMed 17822322Salzman R, Kankova K, Pacal L, Tomandl J, Horakova Z, Kostrica R. Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases. Neoplasma. 2007;54(4):321-5.
- Results publication: PubMed 33587847Uz U, Eskiizmir G. Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review. Clin Exp Otorhinolaryngol. 2021 Feb;14(1):50-60. doi: 10.21053/ceo.2019.00906. Epub 2021 Feb 1.
- Results publication: PubMed 26135695Rettig TC, Verwijmeren L, Dijkstra IM, Boerma D, van de Garde EM, Noordzij PG. Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery. Ann Surg. 2016 Jun;263(6):1207-12. doi: 10.1097/SLA.0000000000001342.
- Results publication: PubMed 29374733Karkkainen J, Selander T, Purdy M, Juvonen P, Eskelinen M. Patients with Increased Levels of the Oxidative Stress Biomarker SOD1 Appear to Have Diminished Postoperative Pain After Midline Laparotomy: A Randomised Trial with Special Reference to Postoperative Pain Score (NRS). Anticancer Res. 2018 Feb;38(2):1003-1008. doi: 10.21873/anticanres.12315.
- Results publication: PubMed 32538771Liu Q, Xu K. Evaluation of some cellular biomarker proteins, oxidative stress and clinical indices as results of laparoscopic appendectomy for perforated appendicitis in children. Cell Mol Biol (Noisy-le-grand). 2020 Jun 5;66(3):197-203.
- Results publication: PubMed 28623906Si HB, Yang TM, Zeng Y, Zhou ZK, Pei FX, Lu YR, Cheng JQ, Shen B. Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty. BMC Musculoskelet Disord. 2017 Jun 17;18(1):265. doi: 10.1186/s12891-017-1597-y.
- Results publication: PubMed 31785250Xi MY, Li SS, Zhang C, Zhang L, Wang T, Yu C. Nalbuphine for Analgesia After Orthognathic Surgery and Its Effect on Postoperative Inflammatory and Oxidative Stress: A Randomized Double-Blind Controlled Trial. J Oral Maxillofac Surg. 2020 Apr;78(4):528-537. doi: 10.1016/j.joms.2019.10.017. Epub 2019 Nov 5.
- Results publication: PubMed 35869710Liu D, Liu H, Wu J, Gong B. Effects of Thoracic Paravertebral Blockon Inflammatory Response, Stress Response, Hemodynamics and Anesthesia Resuscitation inGallbladder Carcinoma. Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):171-177. doi: 10.14715/cmb/2022.68.2.24.
- Individual participant dataSharing planned: Yes. Available and ethical compliant patients data will be submitted to the data repository
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ana D Jotic, MD, PhD study director
Clinic for otorhinolaryngology and maxillofacial surgery, Clinical center of Serbia
Katarina R Savic Vujovic, MD, PhD study director
Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Oxidative Stress Induction and Laryngeal Cancer, run by Clinical Centre of Serbia at 2 sites in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ana D Jotic, MD, PHD (+381 63 7789825, anajotic@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between inflammatory marker IL-1 and pain intensity (time frame: 7 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05857202, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2023.