Ignite Creation Date:
2024-05-06 @ 5:06 PM
Last Modification Date:
2024-10-26 @ 2:22 PM
Study NCT ID:
NCT05193461
Status:
UNKNOWN
Last Update Posted:
2022-01-18
First Post:
2022-01-02
Brief Title:
The Potential Role of SI00B and Brain Derived Neurotrophic Factor in Predicting Outcome From Using Pulsed Radiofrequency in Treatment of Patients With Lumbar Disc Prolapsed
Sponsor:
Beni-Suef University
Organization:
Beni-Suef University
Study Overview
Official Title:
The Potential Role of SI00B and Brain Derived Neurotrophic Factor in Predicting Outcome From Using Pulsed Radiofrequency in Treatment of Patients With Lumbar Disc Prolapsed
Status:
UNKNOWN
Status Verified Date:
2022-01
Last Known Status:
RECRUITING
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:
Chronic lumbar radicular CLR pain is a term used to describe neuropathic pain symptoms in the distribution of a particular lumbar nerve root due to disc protrusion spinal stenosis facet hypertrophy or fibrosis after previous surgery The pathophysiology of CLR pain involves mechanical inflammatory and immunologic factors that affect the function of the dorsal root ganglion DRG1Treatment methods include oral pain medications physical therapy epidural steroid injection ESI and surgery 23
Pulsed radiofrequency PRF was developed as a modification of the well-known radiofrequency ablation treatment In conventional radiofrequency ablation a high frequency alternating current is used to produce coagulative necrosis of the target nerve tissue without any selectivity for nociceptive fibers However in PRF a current in short 20 msec high voltage bursts is followed by silent phases 480 msec which allow for heat dissemination keeping the target tissue controlled below 42C 45 The mechanisms via which PRF causes analgesia are still not clearly understood but laboratory experiments have highlighted some possible ways in which it might act including its effects on neuropathic pain Clinical use of PRF has been expanding despite there being limited evidence of clinical efficacy in the form of randomized controlled trials RCTs 6 There have been few RCTs using PRF-DRG for radicular pain Van Zundert et al performed an RCT in subjects with cervical radicular pain7 Simopoulos et al did a pilot study on lumbar radicular pain but the methodology included application of conventional radiofrequency over PRF in the study group and was not an efficacy trial As such the efficacy of PRF-DRG in CLR has never been determined 8
Neuroplasticity or neuronal plasticity refers to the ability of the nervous system to do neuronal remodeling formation of novel synapses and birth of new neurons Neuronal plasticity is intimately linked to cellular responsiveness and may therefore be considered an index of the neuronal capability to restore its function Failure of such mechanisms might enhance the susceptibility to neuronal injury9 Neurotrophic factors NTFs and in particular the neurotrophin family play an important role In fact besides their classical role in supporting neuronal survival NTFs finely modulate all the crucial steps of network construction from neuronal migration to experience-dependent refinement of local connections It is now well established that NTFs are important mediators of neuronal plasticity also in adulthood where they modulate axonal and dendritic growth and remodeling membrane receptor trafficking neurotransmitter release synapse formation and function10 The neurotrophin brain-derived neurotrophic factor BDNF has emerged as crucial mediator of neuronal plasticity suggesting that it might indeed bridge experience with enduring change in neuronal function11BDNF acts on certain neurons of the central nervous system and the peripheral nervous system helping to support survival of existing neurons and encouraging growth and differentiation of new neurons and synapses1213 S100B belongs to the family ofcalcium binding proteins is expressed mainly by astrocytesand is found both intra- and extracellularly in brain tissue It was also reported that mature myelinating and non-myelinating Schwann cells of peripheral nerves strongly display S100 protein immunoreactivity Stefansson et al 1982 Sugimura et al 1989 Vega et al 199614 S100B can spill from injured cells and enter the extracellular space or bloodstream Serum levels of S100B increase in patients with neuronal damage Over the last decade S100B has emerged as a candidate peripheral biomarker of neuronal injury Elevated S100B levels accurately reflect the presence ofneurodegenerayion Its potential clinical use in the therapeutic decisions is substantiated by a vast body of literature Thus the major advantage of using S100B is that its elevatio in serum provides a sensitive measure for determining neuronal injury at the molecular level before gross changes level15
Pulsed radiofrequency PRF was developed as a modification of the well-known radiofrequency ablation treatment In conventional radiofrequency ablation a high frequency alternating current is used to produce coagulative necrosis of the target nerve tissue without any selectivity for nociceptive fibers However in PRF a current in short 20 msec high voltage bursts is followed by silent phases 480 msec which allow for heat dissemination keeping the target tissue controlled below 42C 45 The mechanisms via which PRF causes analgesia are still not clearly understood but laboratory experiments have highlighted some possible ways in which it might act including its effects on neuropathic pain Clinical use of PRF has been expanding despite there being limited evidence of clinical efficacy in the form of randomized controlled trials RCTs 6 There have been few RCTs using PRF-DRG for radicular pain Van Zundert et al performed an RCT in subjects with cervical radicular pain7 Simopoulos et al did a pilot study on lumbar radicular pain but the methodology included application of conventional radiofrequency over PRF in the study group and was not an efficacy trial As such the efficacy of PRF-DRG in CLR has never been determined 8
Neuroplasticity or neuronal plasticity refers to the ability of the nervous system to do neuronal remodeling formation of novel synapses and birth of new neurons Neuronal plasticity is intimately linked to cellular responsiveness and may therefore be considered an index of the neuronal capability to restore its function Failure of such mechanisms might enhance the susceptibility to neuronal injury9 Neurotrophic factors NTFs and in particular the neurotrophin family play an important role In fact besides their classical role in supporting neuronal survival NTFs finely modulate all the crucial steps of network construction from neuronal migration to experience-dependent refinement of local connections It is now well established that NTFs are important mediators of neuronal plasticity also in adulthood where they modulate axonal and dendritic growth and remodeling membrane receptor trafficking neurotransmitter release synapse formation and function10 The neurotrophin brain-derived neurotrophic factor BDNF has emerged as crucial mediator of neuronal plasticity suggesting that it might indeed bridge experience with enduring change in neuronal function11BDNF acts on certain neurons of the central nervous system and the peripheral nervous system helping to support survival of existing neurons and encouraging growth and differentiation of new neurons and synapses1213 S100B belongs to the family ofcalcium binding proteins is expressed mainly by astrocytesand is found both intra- and extracellularly in brain tissue It was also reported that mature myelinating and non-myelinating Schwann cells of peripheral nerves strongly display S100 protein immunoreactivity Stefansson et al 1982 Sugimura et al 1989 Vega et al 199614 S100B can spill from injured cells and enter the extracellular space or bloodstream Serum levels of S100B increase in patients with neuronal damage Over the last decade S100B has emerged as a candidate peripheral biomarker of neuronal injury Elevated S100B levels accurately reflect the presence ofneurodegenerayion Its potential clinical use in the therapeutic decisions is substantiated by a vast body of literature Thus the major advantage of using S100B is that its elevatio in serum provides a sensitive measure for determining neuronal injury at the molecular level before gross changes level15
Detailed Description:
METHODS
All patientswill be subjected to the following
1 Clinical assessment
1 Detailed history taking regarding duration of pain the presence of discogenic pain radicular pain responseto medical treatment or previous interventional pain management
2 Neurological examination motor and sensory examination
3 Assessment of the severity of the neurological symptoms before 2 week 1 3 and 6 months after the interventional procedure by a physician who will be blinded to the patients condition and the type of intervention
Modified Oswestry Back Disability Score MODI It consisted of low back pain disability index questionnaire about pain intensity personal care lifting standing walking sitting sleeping social life travelling and employmenthomemaking Thus total 10 points each had score range of 0-5 Hence total score had range of 0-50 A high MODI score indicates a more severe functional disability related to the pain
Numeric Rating Scale NRS-11 It is a scale for assessment of intensity of pain It ranged from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain
4 Assessment of patients satisfaction about the intervention2 week 1 3 and 6months after the interventional procedure by a physician who will be blinded to the patients condition and the type of intervention
The Short Assessment of Patient Satisfaction SAPS It consists of seven items assessing the core domains of patient satisfaction which include treatment satisfaction explanation of treatment results clinician care participation in medical decision making respect by the clinician time with the clinician and satisfaction with hospitalclinic care Responses scales are 5-point scales SAPS scores can be interpreted as follows 0 to 10 very dissatisfied 11 to 18 dissatisfied 19 to 26 satisfied 27 to 28 very satisfied
2 Radiological assessment
Magnetic Resonance imaging MRI
Magnetic Resonance imaging of the lumbosacral spine will be performed for all patients included in the study
The following protocols will be used
1 T1- weighted images axial sagittal
2 T2- weighted images axial coronal
3 Fluid attenuated inversion recovery FLAIR sequence 3 Pulsed radio frequency PRF PRF of the dorsal root ganglion DRG will be performed to all participants in this study The procedures will beperformed in the operating room under fluoroscopic guidance following radiation safety standards The dorsal root ganglion of lumbosacral roots will be targeted The patients will be positioned prone Lidocaine 1 will be infiltrated at the skin entry site A 10 cm 22-gauge radiofrequency needle with a 5 mm curved active tip will be used A radiculogram will be done to confirm appropriate placement and DRG will be stimulated for confirmation of the appropriate nerve root involved Proximity of the needle to the DRG will be determined by appropriate sensory stimulation with 50 Hz 04-06 V and motor stimulation at 2 Hz will be used to determine a threshold 15-20 times greater than the sensory threshold to avoid placement near the anterior nerve root A pulsed lesion will be generated by applying 45 V to the DRG for 6 minutes at 42C
4 Laboratory assessment
A Assessment of Brain Derived Neurotrophic Factor BDNF serum level
Venous blood samples will be taken from all included patients before the interventional procedure and kept 30 minutes for clotting then centrifuged at 2000-3000 rpm for 20 minutes Then serum will be separated and kept under -80 c The BDNF levels will be assessed using commercial sandwich-ELISA kits The Microelisastripplatewill be pre-coated with an antibody specific to BDNF Samples will be added to the appropriate Microelisastripplate wells and comoned to specific antibody Then a Horseradish Peroxidase HRP conjugated antibody specific for BDNF will be added to each Microelisastripplate well and incubated Free components will be washed away The TMB substrate solution will be added to each well Only those wells that contain BDNF and HRP conjugated BDNF antibody will appear blue and then turn to yellow after the addition of the stop solution The optical density OD will be measured spectrophotometrically at a wavelength of 450 nm
B Assessment of S100B serum level
All participants will undergo quantitative assessment of serum S100B before the interventional procedure by applying a sandwich enzyme- linked immunoabsorbent assay technique ELISA Assays will be performed at the clinical and chemical pathology department Beni-suef university hospital on an automated ELISA platform Five mL of whole blood will be drawn from all included patients and put into a sterile plain tube The blood samples will be centrifuged for twenty minutes at a speed 2000-3000 rpm The supernatant serum will be collected and stored at -20 C till the time of analysis Standard of S100B will be supplied as 120 microlitre containing 4000ngL of S100B diluted by standard diluents to generate dilution range from 0 to 2000ngL Fifty mL of standard will be added to wells they will be incubated for one hour at room temperature The wells will be washed three times with washing solution phosphate buffered saline PH is from 70 to 72 100 mL of conjugate will be added per each well Each well will be washed again by washing solution five times Fifty mL of substrate A S100B horseradish peroxidase HRP conjugate will be added to each well followed by addition of Fifty mL of substrate B substrate for HRP enzyme containing small amount of 3355 tetramethylbenzidine then the wells will be covered and left at room temperature for ten minutes Finally fifty mL of stop solution sulphuric acid will be added to each well Optical density will be read at 450 nm The standard curve will be constructed using statistical software
All patientswill be subjected to the following
1 Clinical assessment
1 Detailed history taking regarding duration of pain the presence of discogenic pain radicular pain responseto medical treatment or previous interventional pain management
2 Neurological examination motor and sensory examination
3 Assessment of the severity of the neurological symptoms before 2 week 1 3 and 6 months after the interventional procedure by a physician who will be blinded to the patients condition and the type of intervention
Modified Oswestry Back Disability Score MODI It consisted of low back pain disability index questionnaire about pain intensity personal care lifting standing walking sitting sleeping social life travelling and employmenthomemaking Thus total 10 points each had score range of 0-5 Hence total score had range of 0-50 A high MODI score indicates a more severe functional disability related to the pain
Numeric Rating Scale NRS-11 It is a scale for assessment of intensity of pain It ranged from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain
4 Assessment of patients satisfaction about the intervention2 week 1 3 and 6months after the interventional procedure by a physician who will be blinded to the patients condition and the type of intervention
The Short Assessment of Patient Satisfaction SAPS It consists of seven items assessing the core domains of patient satisfaction which include treatment satisfaction explanation of treatment results clinician care participation in medical decision making respect by the clinician time with the clinician and satisfaction with hospitalclinic care Responses scales are 5-point scales SAPS scores can be interpreted as follows 0 to 10 very dissatisfied 11 to 18 dissatisfied 19 to 26 satisfied 27 to 28 very satisfied
2 Radiological assessment
Magnetic Resonance imaging MRI
Magnetic Resonance imaging of the lumbosacral spine will be performed for all patients included in the study
The following protocols will be used
1 T1- weighted images axial sagittal
2 T2- weighted images axial coronal
3 Fluid attenuated inversion recovery FLAIR sequence 3 Pulsed radio frequency PRF PRF of the dorsal root ganglion DRG will be performed to all participants in this study The procedures will beperformed in the operating room under fluoroscopic guidance following radiation safety standards The dorsal root ganglion of lumbosacral roots will be targeted The patients will be positioned prone Lidocaine 1 will be infiltrated at the skin entry site A 10 cm 22-gauge radiofrequency needle with a 5 mm curved active tip will be used A radiculogram will be done to confirm appropriate placement and DRG will be stimulated for confirmation of the appropriate nerve root involved Proximity of the needle to the DRG will be determined by appropriate sensory stimulation with 50 Hz 04-06 V and motor stimulation at 2 Hz will be used to determine a threshold 15-20 times greater than the sensory threshold to avoid placement near the anterior nerve root A pulsed lesion will be generated by applying 45 V to the DRG for 6 minutes at 42C
4 Laboratory assessment
A Assessment of Brain Derived Neurotrophic Factor BDNF serum level
Venous blood samples will be taken from all included patients before the interventional procedure and kept 30 minutes for clotting then centrifuged at 2000-3000 rpm for 20 minutes Then serum will be separated and kept under -80 c The BDNF levels will be assessed using commercial sandwich-ELISA kits The Microelisastripplatewill be pre-coated with an antibody specific to BDNF Samples will be added to the appropriate Microelisastripplate wells and comoned to specific antibody Then a Horseradish Peroxidase HRP conjugated antibody specific for BDNF will be added to each Microelisastripplate well and incubated Free components will be washed away The TMB substrate solution will be added to each well Only those wells that contain BDNF and HRP conjugated BDNF antibody will appear blue and then turn to yellow after the addition of the stop solution The optical density OD will be measured spectrophotometrically at a wavelength of 450 nm
B Assessment of S100B serum level
All participants will undergo quantitative assessment of serum S100B before the interventional procedure by applying a sandwich enzyme- linked immunoabsorbent assay technique ELISA Assays will be performed at the clinical and chemical pathology department Beni-suef university hospital on an automated ELISA platform Five mL of whole blood will be drawn from all included patients and put into a sterile plain tube The blood samples will be centrifuged for twenty minutes at a speed 2000-3000 rpm The supernatant serum will be collected and stored at -20 C till the time of analysis Standard of S100B will be supplied as 120 microlitre containing 4000ngL of S100B diluted by standard diluents to generate dilution range from 0 to 2000ngL Fifty mL of standard will be added to wells they will be incubated for one hour at room temperature The wells will be washed three times with washing solution phosphate buffered saline PH is from 70 to 72 100 mL of conjugate will be added per each well Each well will be washed again by washing solution five times Fifty mL of substrate A S100B horseradish peroxidase HRP conjugate will be added to each well followed by addition of Fifty mL of substrate B substrate for HRP enzyme containing small amount of 3355 tetramethylbenzidine then the wells will be covered and left at room temperature for ten minutes Finally fifty mL of stop solution sulphuric acid will be added to each well Optical density will be read at 450 nm The standard curve will be constructed using statistical software
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