Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06356844
Status:
RECRUITING
Last Update Posted:
2024-05-17
First Post:
2024-03-05
Brief Title:
The Effect of Resolvins on the Resolve of Inflammatory Low Back Pain
Sponsor:
Bezmialem Vakif University
Organization:
Bezmialem Vakif University
Study Overview
Official Title:
The Effect of Adding Oral Resolvins to Patients Undergoing Transforaminal Epidural Steroid Injection for Low Back Pain Treatment
Status:
RECRUITING
Status Verified Date:
2024-05
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:
Brief Summary Inflammatory back pain is a chronic condition localized in the axial spine and sacroiliac joints1 It often accompanies mechanical issues like lumbar disc herniation While non-surgical interventions such as medication physiotherapy and epidural steroid injections are typically the initial approach surgical options may be considered if these prove ineffective2 Resolvins derived from omega-3 fatty acids have shown promise in reducing inflammation and pain They help to resolve inflammatory responses promote tissue repair and decrease disc size potentially reducing the need for surgery34 This clinical trial aims to evaluate the efficacy of adding oral resolvins to transforaminal epidural steroid injections for treating lumbar disc herniation LDH The control group Group C n25 will receive epidural steroids while the study group Group R n25 will receive both oral omega-3 supplementation and epidural steroids on the same day Additionally the study group will continue taking oral omega-3 supplements for six months
The primary outcome measure will be changes in protrudedextruded disc size assessed via MRI with secondary outcomes including pain levels measured by the Numeric Rating Scale NRS and serum cytokine levels IL-6 IL-17 IL-1 beta TNF-alpha over the study period
Discussion This trial anticipates that combining the anti-inflammatory properties of resolvins with epidural steroid injection will provide a beneficial treatment for patients suffering from inflammatory low back pain
The primary outcome measure will be changes in protrudedextruded disc size assessed via MRI with secondary outcomes including pain levels measured by the Numeric Rating Scale NRS and serum cytokine levels IL-6 IL-17 IL-1 beta TNF-alpha over the study period
Discussion This trial anticipates that combining the anti-inflammatory properties of resolvins with epidural steroid injection will provide a beneficial treatment for patients suffering from inflammatory low back pain
Detailed Description:
In the general population about 70 to 80 of adults experience low back pain at some point in their lives In primary care the point prevalence ranges from 16 to 55 making low back pain the most common neuropathic pain5 In this context radiculopathy is a common type of neuropathic pain Pain can arise not only from direct mechanical pressure such as from a herniated disc or degenerated bone but also from inflammation and its associated proinflammatory cytokines Inflammatory mediators contributing to neuropathic pain include nucleus pulpous cells and sequestered macrophages67 Cytokines as regulatory proteins acting as pro-inflammatory biomarkers modulate the inflammatory response of all immune system cells during instances of inflammation8 Despite its high prevalence the response to medical treatment physical therapy and epidural steroid injections varies widely For years the widely accepted explanation for this variability has been the complex mechanisms involved in pain transmission However in recent years it has been increasingly recognized that the lack of resolution of neuroinflammatory cells and mediators may be the most significant factor contributing to the varying treatment responses observed in individuals9 Resolvins are specialized compounds derived from DHA docosahexaenoic acid and omega-3 fatty acids Prior research indicates that certain resolvin subtypes particularly D and E aid in pain reduction by facilitating inflammation resolution These specialized compounds known as SPMs Specialized pro-resolving mediators regulate immune cell functions modulate cytokine levels and promote tissue repair mechanisms 910 The aim of this study is to evaluate the impact of orally administered resolvins in conjunction with epidural steroid injection over a period of 6 months on pain intensity and cytokine release during the remission phase These effects will be assessed using magnetic resonance imaging
Materials and Methods This clinical trial will be a randomized controlled trial conducted at Bezmialem Vakıf University Hospital A total of 30 patients will be enrolled in the study at this hospital The study has received approval from the Ethics Boards of Bezmialem Vakif University Hospital Prior to participation all study participants will provide written informed consent
Inclusion criteria Patients must be classified as ASA I-II-III aged between 18-75 presenting to the Algology department with low back pain due to lumbar disc herniation have a pain intensity of 4 on the 0-10 scale pain NRS for low back pain andor experience radiating pain from the lower extremities caused by LDH MRI scan confirmed lumbar disc herniation in our hospital
Exclusion Criteria Patients with known allergies to the drugs to be used in treatment infection near the puncture site known clotting disorders alcohol and drug use those who have used fish oil before disorder of consciousness liver failure renal failure advanced cardiac failure uncontrolled diabetes mellitus morbid obesity body mass index BMI 35 kgm² female patients during pregnancy and breastfeeding not approving the informed consent form
30 patients scheduled for caudal epidural injection transforaminal epidural steroid injection will be included Patients will be randomly assigned to two groups Group K control group Group R patients treated with resolvin using opaque sealed envelopes The physician performing the procedure AT and collecting data AB will be blinded to the groups In Group R treatment with 700 mg resolvin omega DHA will commence on the day the procedural decision is made
Intervention After the patient is admitted to the ward on the morning of the procedure they will undergo routine blood tests including a hemogram APTT INR CRP and sedimentation test Once the results are obtained the patient will be sent for the operation Upon arrival in the operating room basic monitoring including ECG non-invasive blood pressure and pulse oximetry will be performed The operating room will be standardized and normothermia will be maintained Patients will be positioned prone on the operating table and nasal oxygen support at 4Lmin will be provided After administering sedation and analgesia prophylactic antibiotics will be given The operative site will be prepared with an antiseptic solution and draped sterilely All procedures are performed with the assistance of ultrasonography using a convex probe After local anesthesia is applied to the areas to be treated the procedure begins with a caudal epidural injection consisting of 40mg depomedrol 60mg lidocaine 20mg bupivacaine and 100mg magnesium Following this the transforaminal epidural injection is administered with 2mg dexamethasone 20mg lidocaine 5mg bupivacaine and 100mg magnesium The same doses are applied to the facet insertion as the needle is withdrawn After completion of the procedure patients will be monitored in the recovery room for half an hour followed by mobilization and transfer to the ward Stable hemodynamics and absence of neurological deficits and any other complications nausea bradycardia hypotension urinary incontinence drowsiness bleeding neurological deficit edema dyspeptic complaints due to fish oil or steroids will warrant discharge after 6 hours
Blood samples will be collected from the patients on the morning of the procedure day during the one-week follow-up appointment after the procedure and during the six-month follow-up along with MRI Additionally all medications used by patients during this period will be recorded
Primary The primary objective of this study Magnetic Resonance Imaging MRI is the gold standard for diagnosing lumbar disc herniation with a diagnostic accuracy rate of 97 It is also a crucial parameter used to determine the need for surgical intervention MRI imaging will be used to measure the size of herniation preoperatively and at the 6th postoperative month by a radiologist who is blinded to the patient groups AA
Secondary objective of this study
1 NRS Score The Numeric Rating Scale NRS is a unidimensional scale using 11 numbers ranging from 0 to 10 to assess pain intensity Patients are asked to select the number that best represents their pain intensity with 0 indicating no pain and 10 indicating the worst unbearable pain Pain intensity will be assessed by having patients choose the number that corresponds to their pain intensity Pain levels of all patients at the 1st postoperative week 1st month and 6th month will be recorded based on the NRS score by an anesthesiologist who is blinded to the patient groups
2 Cytokines Cytokines are small proteins synthesized by cells responsible for intercellular communication and interaction They include various subtypes such as interleukins The majority of studies found a positive association between the pro-inflammatory biomarkers CRP IL-6 TNF-a and low back pain Blood tests for cytokine levels Interleukin-6 Interleukin-17 Interleukin-1beta TNF-alpha were conducted preoperatively at the 1st postoperative week and at the 6th month by a medical biochemist who was blinded to the patient groups
Statistics Power analysis Based on previous studies and considering an average difference of 050 units between groups with 80 power at a 95 confidence level the minimum sample size was determined as 13 individuals per group totaling 26 participants Qualitative variables will be presented as numbers and percentages while quantitative variables will be expressed as mean standard deviation median minimum and maximum The relationships between qualitative variables will be examined using Pearson chi-square or Fisher exact chi-square tests Normal distribution of quantitative variables will be assessed using the Kolmogorov-Smirnov test and homogeneity of variance will be evaluated using the Levene test Differences between the means of two independent groups will be analyzed using the Students t-test while median comparisons will be conducted using the Mann-Whitney U test Paired t-tests and Wilcoxon signed-rank tests will be employed for comparing means and medians of two dependent groups respectively Following univariate analyses appropriate regression analyses will be utilized based on the data structure Calculations will be performed using the SPSS software package version with a statistical significance level set at 005
Discussion This trial anticipates that combining the anti-inflammatory properties of resolvins with epidural steroid injection will provide a beneficial treatment for patients suffering from inflammatory low back pain This study demonstrates that two separate mechanisms result including the decrease in cell recruitment to the inflammation site with steroids which reflects an anti-inflammatory effect and increases in cell exit with resolvin which reflects a pro-resolution effect
References
1 Lassiter W Allam AE Inflammatory Back Pain Stat Pearls Internet Treasure Island FL Stat Pearls Publishing 2023 Jan- 2022 Sep 5 PMID 30969575
2 Taso M Sommernes JH Kolstad F Sundseth J Bjorland S Pripp AH Zwart JA Brox JI A randomized controlled trial comparing the effectiveness of surgical and nonsurgical treatment for cervical radiculopathy BMC Musculoskeletal Disorder 2020 Mar 16211171 PMID 32178655 PMCID PMC7076994
3 Ji RR Xu ZZ Strichartz G Serhan CN Emerging roles of resolvins in the resolution of inflammation and pain Trends Neurosci 2011 Nov3411599-609 PMID 21963090 PMCID PMC3200462
4 Liu C Fan D Lei Q Lu A He X Roles of Resolvins in Chronic Inflammatory Response Int J Mol Sci 2022 Nov 28232314883 PMID 36499209 PMCID PMC9738788
5 Yoshiaki Ota Michael Connolly Ashok Srinivasan John Kim Aristides A Capizzano Toshio Moritani Mechanisms and origins of spinal pain from molecules to anatomy with diagnostic clues and imaging findings Radiographic Jul-Aug 20204041163-1181
6 Sowa GA Coelho JP Vo NV Pacek C Westrick E Kang JD Cells from degenerative intervertebral discs demonstrate unfavorable responses to mechanical and inflammatory stimuli a pilot study Am J Phys Med Rehabil 201291846-855
7 Videman T Saarela J Kaprio J et al Associations of 25 structural degradative and inflammatory candidate genes with lumbar disc desiccation bulging and height narrowing Arthritis Rheum 200960470-4818
8 R van den Berg 1 E M Jongbloed 2 E I T de Schepper 2 S M A Bierma-Zeinstra 3 B W Koes 2 P A J Luijsterburg The association between pro-inflammatory biomarkers and nonspecific low back pain a systematic review Spine J 2018 Nov18112140-215
9 Ru-Rong Ji1 Zhen-Zhong Xu1 Gary Strichartz1 and Charles N Serhan2 Emerging Roles of Resolvins in the Resolution of Inflammation and Pain Trends Neurosci 2011 November 3411 599-609 doi101016jtins201108005
10 Chang Liu 12 Dancai Fan 3 Qian Lei 13 Aiping Lu 145 and Xiaojuan He 3 Roles of Resolvins in Chronic Inflammatory Response Int J Mol Sci 2022 23 14883 httpsdoiorg103390ijms232314883
11 Simon C Le Corroller T Pauly V Creze M Champsaur P Guenoun D Intradiscal oxygen-ozone therapy for the treatment of symptomatic lumbar disc herniation A preliminary study J Neuroradiol 2022 Mar492180-186 doi 101016jneurad202109004 Epub 2021 Oct 8 PMID 34634298
Materials and Methods This clinical trial will be a randomized controlled trial conducted at Bezmialem Vakıf University Hospital A total of 30 patients will be enrolled in the study at this hospital The study has received approval from the Ethics Boards of Bezmialem Vakif University Hospital Prior to participation all study participants will provide written informed consent
Inclusion criteria Patients must be classified as ASA I-II-III aged between 18-75 presenting to the Algology department with low back pain due to lumbar disc herniation have a pain intensity of 4 on the 0-10 scale pain NRS for low back pain andor experience radiating pain from the lower extremities caused by LDH MRI scan confirmed lumbar disc herniation in our hospital
Exclusion Criteria Patients with known allergies to the drugs to be used in treatment infection near the puncture site known clotting disorders alcohol and drug use those who have used fish oil before disorder of consciousness liver failure renal failure advanced cardiac failure uncontrolled diabetes mellitus morbid obesity body mass index BMI 35 kgm² female patients during pregnancy and breastfeeding not approving the informed consent form
30 patients scheduled for caudal epidural injection transforaminal epidural steroid injection will be included Patients will be randomly assigned to two groups Group K control group Group R patients treated with resolvin using opaque sealed envelopes The physician performing the procedure AT and collecting data AB will be blinded to the groups In Group R treatment with 700 mg resolvin omega DHA will commence on the day the procedural decision is made
Intervention After the patient is admitted to the ward on the morning of the procedure they will undergo routine blood tests including a hemogram APTT INR CRP and sedimentation test Once the results are obtained the patient will be sent for the operation Upon arrival in the operating room basic monitoring including ECG non-invasive blood pressure and pulse oximetry will be performed The operating room will be standardized and normothermia will be maintained Patients will be positioned prone on the operating table and nasal oxygen support at 4Lmin will be provided After administering sedation and analgesia prophylactic antibiotics will be given The operative site will be prepared with an antiseptic solution and draped sterilely All procedures are performed with the assistance of ultrasonography using a convex probe After local anesthesia is applied to the areas to be treated the procedure begins with a caudal epidural injection consisting of 40mg depomedrol 60mg lidocaine 20mg bupivacaine and 100mg magnesium Following this the transforaminal epidural injection is administered with 2mg dexamethasone 20mg lidocaine 5mg bupivacaine and 100mg magnesium The same doses are applied to the facet insertion as the needle is withdrawn After completion of the procedure patients will be monitored in the recovery room for half an hour followed by mobilization and transfer to the ward Stable hemodynamics and absence of neurological deficits and any other complications nausea bradycardia hypotension urinary incontinence drowsiness bleeding neurological deficit edema dyspeptic complaints due to fish oil or steroids will warrant discharge after 6 hours
Blood samples will be collected from the patients on the morning of the procedure day during the one-week follow-up appointment after the procedure and during the six-month follow-up along with MRI Additionally all medications used by patients during this period will be recorded
Primary The primary objective of this study Magnetic Resonance Imaging MRI is the gold standard for diagnosing lumbar disc herniation with a diagnostic accuracy rate of 97 It is also a crucial parameter used to determine the need for surgical intervention MRI imaging will be used to measure the size of herniation preoperatively and at the 6th postoperative month by a radiologist who is blinded to the patient groups AA
Secondary objective of this study
1 NRS Score The Numeric Rating Scale NRS is a unidimensional scale using 11 numbers ranging from 0 to 10 to assess pain intensity Patients are asked to select the number that best represents their pain intensity with 0 indicating no pain and 10 indicating the worst unbearable pain Pain intensity will be assessed by having patients choose the number that corresponds to their pain intensity Pain levels of all patients at the 1st postoperative week 1st month and 6th month will be recorded based on the NRS score by an anesthesiologist who is blinded to the patient groups
2 Cytokines Cytokines are small proteins synthesized by cells responsible for intercellular communication and interaction They include various subtypes such as interleukins The majority of studies found a positive association between the pro-inflammatory biomarkers CRP IL-6 TNF-a and low back pain Blood tests for cytokine levels Interleukin-6 Interleukin-17 Interleukin-1beta TNF-alpha were conducted preoperatively at the 1st postoperative week and at the 6th month by a medical biochemist who was blinded to the patient groups
Statistics Power analysis Based on previous studies and considering an average difference of 050 units between groups with 80 power at a 95 confidence level the minimum sample size was determined as 13 individuals per group totaling 26 participants Qualitative variables will be presented as numbers and percentages while quantitative variables will be expressed as mean standard deviation median minimum and maximum The relationships between qualitative variables will be examined using Pearson chi-square or Fisher exact chi-square tests Normal distribution of quantitative variables will be assessed using the Kolmogorov-Smirnov test and homogeneity of variance will be evaluated using the Levene test Differences between the means of two independent groups will be analyzed using the Students t-test while median comparisons will be conducted using the Mann-Whitney U test Paired t-tests and Wilcoxon signed-rank tests will be employed for comparing means and medians of two dependent groups respectively Following univariate analyses appropriate regression analyses will be utilized based on the data structure Calculations will be performed using the SPSS software package version with a statistical significance level set at 005
Discussion This trial anticipates that combining the anti-inflammatory properties of resolvins with epidural steroid injection will provide a beneficial treatment for patients suffering from inflammatory low back pain This study demonstrates that two separate mechanisms result including the decrease in cell recruitment to the inflammation site with steroids which reflects an anti-inflammatory effect and increases in cell exit with resolvin which reflects a pro-resolution effect
References
1 Lassiter W Allam AE Inflammatory Back Pain Stat Pearls Internet Treasure Island FL Stat Pearls Publishing 2023 Jan- 2022 Sep 5 PMID 30969575
2 Taso M Sommernes JH Kolstad F Sundseth J Bjorland S Pripp AH Zwart JA Brox JI A randomized controlled trial comparing the effectiveness of surgical and nonsurgical treatment for cervical radiculopathy BMC Musculoskeletal Disorder 2020 Mar 16211171 PMID 32178655 PMCID PMC7076994
3 Ji RR Xu ZZ Strichartz G Serhan CN Emerging roles of resolvins in the resolution of inflammation and pain Trends Neurosci 2011 Nov3411599-609 PMID 21963090 PMCID PMC3200462
4 Liu C Fan D Lei Q Lu A He X Roles of Resolvins in Chronic Inflammatory Response Int J Mol Sci 2022 Nov 28232314883 PMID 36499209 PMCID PMC9738788
5 Yoshiaki Ota Michael Connolly Ashok Srinivasan John Kim Aristides A Capizzano Toshio Moritani Mechanisms and origins of spinal pain from molecules to anatomy with diagnostic clues and imaging findings Radiographic Jul-Aug 20204041163-1181
6 Sowa GA Coelho JP Vo NV Pacek C Westrick E Kang JD Cells from degenerative intervertebral discs demonstrate unfavorable responses to mechanical and inflammatory stimuli a pilot study Am J Phys Med Rehabil 201291846-855
7 Videman T Saarela J Kaprio J et al Associations of 25 structural degradative and inflammatory candidate genes with lumbar disc desiccation bulging and height narrowing Arthritis Rheum 200960470-4818
8 R van den Berg 1 E M Jongbloed 2 E I T de Schepper 2 S M A Bierma-Zeinstra 3 B W Koes 2 P A J Luijsterburg The association between pro-inflammatory biomarkers and nonspecific low back pain a systematic review Spine J 2018 Nov18112140-215
9 Ru-Rong Ji1 Zhen-Zhong Xu1 Gary Strichartz1 and Charles N Serhan2 Emerging Roles of Resolvins in the Resolution of Inflammation and Pain Trends Neurosci 2011 November 3411 599-609 doi101016jtins201108005
10 Chang Liu 12 Dancai Fan 3 Qian Lei 13 Aiping Lu 145 and Xiaojuan He 3 Roles of Resolvins in Chronic Inflammatory Response Int J Mol Sci 2022 23 14883 httpsdoiorg103390ijms232314883
11 Simon C Le Corroller T Pauly V Creze M Champsaur P Guenoun D Intradiscal oxygen-ozone therapy for the treatment of symptomatic lumbar disc herniation A preliminary study J Neuroradiol 2022 Mar492180-186 doi 101016jneurad202109004 Epub 2021 Oct 8 PMID 34634298
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