Ignite Creation Date:
2024-05-06 @ 7:52 PM
Last Modification Date:
2024-10-26 @ 3:16 PM
Study NCT ID:
NCT06169488
Status:
RECRUITING
Last Update Posted:
2024-05-01
First Post:
2023-11-22
Brief Title:
The Lumbar Interbody Fusion vs Multidisciplinary Rehabilitation LIFEHAB Trial
Sponsor:
Oslo University Hospital
Organization:
Oslo University Hospital
Study Overview
Official Title:
The Lumbar Interbody Fusion vs Multidisciplinary Rehabilitation LIFEHAB Trial
Status:
RECRUITING
Status Verified Date:
2024-04
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:
LIFEHAB
Brief Summary:
The goal of this randomized controlled trial is to compare lumbar interbody fusion surgery with multidisciplinary rehabilitation in participants aged 20-65 years with persisting one year low back pain The main question it aims to answer is
Is lumbar fusion surgery superior to multidisciplinary rehabilitation in alleviating persisting low back pain
Participants will be randomized to either lumbar interbody fusion surgery or a multidisciplinary rehabilitation program
If randomized to lumbar fusion interbody surgery the participants will
undergo radiologic examinations including X-ray MRI and MRI spectroscopy
provide blood samples at four intervals including postoperatively
complete PROMs at five intervals
have their activity monitored through the ActivePAL accelerometer
undergo lumbar fusion surgery
If randomized to multidisciplinary rehabilitation the participants will
undergo radiologic examinations including X-ray MRI and MRI spectroscopy
provide blood samples at three intervals
complete PROMs at five intervals
have their activity monitored through the ActivePAL accelerometer
undergo multidisciplinary rehabilitation
Is lumbar fusion surgery superior to multidisciplinary rehabilitation in alleviating persisting low back pain
Participants will be randomized to either lumbar interbody fusion surgery or a multidisciplinary rehabilitation program
If randomized to lumbar fusion interbody surgery the participants will
undergo radiologic examinations including X-ray MRI and MRI spectroscopy
provide blood samples at four intervals including postoperatively
complete PROMs at five intervals
have their activity monitored through the ActivePAL accelerometer
undergo lumbar fusion surgery
If randomized to multidisciplinary rehabilitation the participants will
undergo radiologic examinations including X-ray MRI and MRI spectroscopy
provide blood samples at three intervals
complete PROMs at five intervals
have their activity monitored through the ActivePAL accelerometer
undergo multidisciplinary rehabilitation
Detailed Description:
Background Low back pain LBP is the number one cause of disability worldwide Chronic LBP cLBP also referred to as persisting low back pain is defined as low back pain lasting at least twelve weeks with a lifetime prevalence of about 23 It represents extensive individual societal and financial burdens
The etiology of cLBP is multifactorial with complex pathogenesis and only a small proportion of patients with disabling cLBP have a well-understood pathophysiological cause Over the last several decades the biopsychosocial model of LBP has been the standard approach Accordingly current clinical guidelines recommend treatments such as advice to stay active exercise reassurance and coping strategies analgesic medications and avoiding bed rest The existing treatments however have only small to moderate effects and 85-90 of patients do not receive a pathoanatomical diagnosis National Institute for Health and Care Excellence NICE
Many pathophysiological hypotheses for cLBP have been proposed eg annular tear disc herniation loss of disc height facet joint degeneration and Modic changes For example it has been hypothesized that cLBP with Modic changes is caused by bacterial infection A Danish trial reported that antibiotic treatment was superior to placebo in selected cLBP patients with focal vertebral bone marrow changes Modic changes graded by MRI of the lumbar spine However the Norwegian AIM Antibiotic In Modic changes study did not support this finding Nonetheless intervertebral disc IVD degeneration is generally accepted as a relevant cause of cLBP especially among surgeons treating the condition An experimental study of cultured human nucleus pulposus cells showed that acidic pH caused an increase in several pro-inflammatory neurotrophic and pain-related factors This upregulation of inflammatory substances may in turn induce the ingrowth of nerve fibers into degenerative IVDs possibly explaining how discs can become painful Therefore one possible approach to diagnose painful IVDs could be to measure IVD pH levels by MRI spectroscopy MRS The local inflammation in degenerative IVD is correlated with a systemic inflammatory response that can be measured in serum samples and is related to symptoms Recent developments in diagnostics and biomarkers in the field may improve patient selection and support an individually tailored treatment
A few randomized controlled trials have compared lumbar spine fusion with non-operative treatment finding similar improvements in pain and disability for both treatment alternatives This has led to guidelines recommending non-operative treatment
The researchers in the current project aim to improve treatment develop refined diagnostic assessments and explore potential biomarkers in a multicenter randomized controlled trial RCT adding level-one evidence to the subject
The overall concept is to assess whether there is a difference in treatment effect between modern lumbar interbody fusion LIF and multidisciplinary rehabilitation MRE for patients with cLBP The researchers aim to
Evaluate the effect of LIF versus MRE at one-year follow-up FU
Evaluate the treatment effectiveness at two-year FU in the cohort of patients crossing over from one treatment arm to the other at one-year FU Primary and secondary outcome measures will be the same as those listed in sections 1 through 12 of the Outcome Measures section
Evaluate the effect of LIF versus MRE at one-year FU on physical activity sleep disturbances and circadian rhythm
Evaluate whether baseline MRS biomarkers are associated with treatment response after LIF at one-year FU
Evaluate whether baseline MRS biomarkers are associated with treatment response after MRE at one-year FU
Evaluate whether MRS biomarkers are associated with molecular biomarkers in blood samples collected at three time points
Evaluate if molecular biomarkers can identify patients with improvement after LIF at one-year FU
Evaluate if molecular biomarkers can identify patients with improvement after MRE at one-year FU
Evaluate if feasible the correlation between MRS biomarkers and perioperative pH measurement of the IVD
Evaluate the cost-effectiveness of LIF versus MRE from baseline to one-year FU The spinal surgeons will screen participants for trial eligibility by predetermined inclusion- and exclusion criteria and ensure that necessary imaging examinations MRI and X-ray have been done per protocol
Patients will be invited to trial participation if all the inclusion criteria and none of the exclusion criteria are satisfied Patients who may be relevant study candidates are set up for a new appointment with another surgeon associated with the project so that each potential participant receives an individual assessment by two different surgeons ensuring a thorough evaluation and sufficient reflection period for the patient To avoid undue pressure to participate in the study one of the treating surgeons who have assessed the patient at the outpatient clinic will provide information about the project and obtaining informed consent will be done by an independent third party for example a study nurse a representative from rehabilitation or another surgeon associated with the project To ensure comprehensive and unbiased information regarding both trial arms representatives from the MRE arm will also have a face-to-face or electronic meeting with potential trial participants before their inclusion General consent as well as specific consent to the neuroscientific biobank will be obtained However consent to the neuroscience biobank is not mandatory for study participation The participant will be issued copies of the letter informing about the trial and the signed informed consents
Eligible patients will be allocated in a 11 ratio between LIF and MRE using a computer randomization procedure stratified by center Block size and allocation sequence generation details will be provided in a separate document unavailable to those who enroll patients or assign treatment Following screening eligible participants will be randomized in a continuous manner Treatment initiation will occur within three months of randomization for both treatment groups
Baseline data collection will include sociodemographic variables age gender BMI ethnicity educational level work status as well as information on physical workload leisure activities smoking habits emotional distress assessed with Hopkins Symptom Checklist-25 HSCL-25 fear avoidance beliefs FABQ Örebro Musculoskeletal Pain Screening Questionnaire Short-form and cLBP history including duration and prior treatments such as spinal surgery physiotherapy and chiropractic therapy At baseline we will ask all participants to report their smallest worthwhile reduction of pain and disability in percent not specified to measurement instrument what treatment group they hope to be randomized to and how well they expect to be at one-year FU Likert scale 1-7 We will further ask all investigators at baseline to report what treatment allocation they think would be best for the individual participant if they were not participating in a study and to rate Likert scale 1-7 how well they expect the participant to be at one-year FU given the randomization
Baseline sick listing and subsequent sick listing at each FU consultation will include documentation of complete work absence and part-time absence
Prospective participants must undergo radiological examinations before study inclusion including MRI and plain radiographs for measuring pelvic spine parameters The MRI and radiographs must be obtained within six months before the initiation of treatment
Hematological parameters leucocytes thrombocytes hemoglobin Hb sedimentation rate CRP electrolytes Na and K and measures of kidney creatinine and liver function ALAT will be assessed and registered at baseline if allocated to LIF intervention Functional comorbidity index will be reported at screening and serve as a screening tool for other relevant illnesses together with physical examination at baseline
The study will be monitored by the Clinical Trial Unit at Oslo University Hospital according to the standard by NorCRIN and Good Clinical Practice Adverse events and serious adverse events will be registered at all study FUs The study will focus on monitoring specific adverse events in individuals allocated to the LIF intervention These events include the following
Deep and superficial wound infection and rupture of the surgical wound
Hardware mechanical complications with loosening of pedicle screws and interbody implants before bony fusion of the addressed lumbar level are evidenced
Improper hardware placement
Wrong-level surgery
Dural tears leading to spinal headaches and possibly a pseudo-meningocele
Nerve root injury possibly leading to chronic neuropathic pain palsy and dysfunction of the muscles affected
Postoperative spinal hematoma necessitating an acute surgical evacuation
Cauda equina compression that may lead to transient or permanent dysfunction of the urinary bladder and bowel function
Potentially life-threatening hemorrhage by iatrogenic injury to large pelvic vessels
Iatrogenic injury to the ureter necessitating additional urologic procedures
Bowel perforation in case of ALIF
Retrograde ejaculation due to iatrogenic injury to the lumbar autonomous nervous system ALIF Monitoring for these adverse events will involve clinical examination blood sample analysis including parameters such as Hb CRP and leukocytes and radiologic imaging such as CT scans and MRI
Blood samples for DNA genotyping Genomics methylation Epigenetics and RNA sequencing Transcriptomics will be collected at baseline 6- and 12-months FU from participants who have consented to participate in the genetic analysis component of the study Participation is optional Participants who do not wish to participate in the genetic research may still participate in the study
The researchers will also at baseline 6- and 12 months measure a panel of 40 cytokines by duplicate serum analysis with a 40-plex Pro Human Chemokine multi-bead assay Samples that can be used to analyze suspected molecular biomarkers in the future will also be collected
For all participants throughout the study the investigator and study site personnel will collect data about healthcare resource utilization associated with medical encounters The cost-benefit analysis of LIF versus MRE will be assessed by QUALYs derived from EQ-5D-5L and hospital and community treatment costs The following data will be collected
LIF Time in theatre duration of surgery blood loss and transfusions number of surgeons anesthesiologists and nurses implant costs length of sick leave use of non-operative treatment ie physiotherapy rehabilitation additional visits to the GP additional follow-ups including imaging outside the study protocol
MRE Medical consultations at the general practitioner or other primary care treatment additional diagnostic tests eg X-ray MRI CT laboratory tests medications eg pain relievers muscle relaxants anti-inflammatories antidepressants time spent at treatment facilities staffing costs travel expenses for patients traveling to rehabilitation institution for every treatment day or session accommodation costs for patients staying at the rehabilitation institution during the treatment period and sick leave
The etiology of cLBP is multifactorial with complex pathogenesis and only a small proportion of patients with disabling cLBP have a well-understood pathophysiological cause Over the last several decades the biopsychosocial model of LBP has been the standard approach Accordingly current clinical guidelines recommend treatments such as advice to stay active exercise reassurance and coping strategies analgesic medications and avoiding bed rest The existing treatments however have only small to moderate effects and 85-90 of patients do not receive a pathoanatomical diagnosis National Institute for Health and Care Excellence NICE
Many pathophysiological hypotheses for cLBP have been proposed eg annular tear disc herniation loss of disc height facet joint degeneration and Modic changes For example it has been hypothesized that cLBP with Modic changes is caused by bacterial infection A Danish trial reported that antibiotic treatment was superior to placebo in selected cLBP patients with focal vertebral bone marrow changes Modic changes graded by MRI of the lumbar spine However the Norwegian AIM Antibiotic In Modic changes study did not support this finding Nonetheless intervertebral disc IVD degeneration is generally accepted as a relevant cause of cLBP especially among surgeons treating the condition An experimental study of cultured human nucleus pulposus cells showed that acidic pH caused an increase in several pro-inflammatory neurotrophic and pain-related factors This upregulation of inflammatory substances may in turn induce the ingrowth of nerve fibers into degenerative IVDs possibly explaining how discs can become painful Therefore one possible approach to diagnose painful IVDs could be to measure IVD pH levels by MRI spectroscopy MRS The local inflammation in degenerative IVD is correlated with a systemic inflammatory response that can be measured in serum samples and is related to symptoms Recent developments in diagnostics and biomarkers in the field may improve patient selection and support an individually tailored treatment
A few randomized controlled trials have compared lumbar spine fusion with non-operative treatment finding similar improvements in pain and disability for both treatment alternatives This has led to guidelines recommending non-operative treatment
The researchers in the current project aim to improve treatment develop refined diagnostic assessments and explore potential biomarkers in a multicenter randomized controlled trial RCT adding level-one evidence to the subject
The overall concept is to assess whether there is a difference in treatment effect between modern lumbar interbody fusion LIF and multidisciplinary rehabilitation MRE for patients with cLBP The researchers aim to
Evaluate the effect of LIF versus MRE at one-year follow-up FU
Evaluate the treatment effectiveness at two-year FU in the cohort of patients crossing over from one treatment arm to the other at one-year FU Primary and secondary outcome measures will be the same as those listed in sections 1 through 12 of the Outcome Measures section
Evaluate the effect of LIF versus MRE at one-year FU on physical activity sleep disturbances and circadian rhythm
Evaluate whether baseline MRS biomarkers are associated with treatment response after LIF at one-year FU
Evaluate whether baseline MRS biomarkers are associated with treatment response after MRE at one-year FU
Evaluate whether MRS biomarkers are associated with molecular biomarkers in blood samples collected at three time points
Evaluate if molecular biomarkers can identify patients with improvement after LIF at one-year FU
Evaluate if molecular biomarkers can identify patients with improvement after MRE at one-year FU
Evaluate if feasible the correlation between MRS biomarkers and perioperative pH measurement of the IVD
Evaluate the cost-effectiveness of LIF versus MRE from baseline to one-year FU The spinal surgeons will screen participants for trial eligibility by predetermined inclusion- and exclusion criteria and ensure that necessary imaging examinations MRI and X-ray have been done per protocol
Patients will be invited to trial participation if all the inclusion criteria and none of the exclusion criteria are satisfied Patients who may be relevant study candidates are set up for a new appointment with another surgeon associated with the project so that each potential participant receives an individual assessment by two different surgeons ensuring a thorough evaluation and sufficient reflection period for the patient To avoid undue pressure to participate in the study one of the treating surgeons who have assessed the patient at the outpatient clinic will provide information about the project and obtaining informed consent will be done by an independent third party for example a study nurse a representative from rehabilitation or another surgeon associated with the project To ensure comprehensive and unbiased information regarding both trial arms representatives from the MRE arm will also have a face-to-face or electronic meeting with potential trial participants before their inclusion General consent as well as specific consent to the neuroscientific biobank will be obtained However consent to the neuroscience biobank is not mandatory for study participation The participant will be issued copies of the letter informing about the trial and the signed informed consents
Eligible patients will be allocated in a 11 ratio between LIF and MRE using a computer randomization procedure stratified by center Block size and allocation sequence generation details will be provided in a separate document unavailable to those who enroll patients or assign treatment Following screening eligible participants will be randomized in a continuous manner Treatment initiation will occur within three months of randomization for both treatment groups
Baseline data collection will include sociodemographic variables age gender BMI ethnicity educational level work status as well as information on physical workload leisure activities smoking habits emotional distress assessed with Hopkins Symptom Checklist-25 HSCL-25 fear avoidance beliefs FABQ Örebro Musculoskeletal Pain Screening Questionnaire Short-form and cLBP history including duration and prior treatments such as spinal surgery physiotherapy and chiropractic therapy At baseline we will ask all participants to report their smallest worthwhile reduction of pain and disability in percent not specified to measurement instrument what treatment group they hope to be randomized to and how well they expect to be at one-year FU Likert scale 1-7 We will further ask all investigators at baseline to report what treatment allocation they think would be best for the individual participant if they were not participating in a study and to rate Likert scale 1-7 how well they expect the participant to be at one-year FU given the randomization
Baseline sick listing and subsequent sick listing at each FU consultation will include documentation of complete work absence and part-time absence
Prospective participants must undergo radiological examinations before study inclusion including MRI and plain radiographs for measuring pelvic spine parameters The MRI and radiographs must be obtained within six months before the initiation of treatment
Hematological parameters leucocytes thrombocytes hemoglobin Hb sedimentation rate CRP electrolytes Na and K and measures of kidney creatinine and liver function ALAT will be assessed and registered at baseline if allocated to LIF intervention Functional comorbidity index will be reported at screening and serve as a screening tool for other relevant illnesses together with physical examination at baseline
The study will be monitored by the Clinical Trial Unit at Oslo University Hospital according to the standard by NorCRIN and Good Clinical Practice Adverse events and serious adverse events will be registered at all study FUs The study will focus on monitoring specific adverse events in individuals allocated to the LIF intervention These events include the following
Deep and superficial wound infection and rupture of the surgical wound
Hardware mechanical complications with loosening of pedicle screws and interbody implants before bony fusion of the addressed lumbar level are evidenced
Improper hardware placement
Wrong-level surgery
Dural tears leading to spinal headaches and possibly a pseudo-meningocele
Nerve root injury possibly leading to chronic neuropathic pain palsy and dysfunction of the muscles affected
Postoperative spinal hematoma necessitating an acute surgical evacuation
Cauda equina compression that may lead to transient or permanent dysfunction of the urinary bladder and bowel function
Potentially life-threatening hemorrhage by iatrogenic injury to large pelvic vessels
Iatrogenic injury to the ureter necessitating additional urologic procedures
Bowel perforation in case of ALIF
Retrograde ejaculation due to iatrogenic injury to the lumbar autonomous nervous system ALIF Monitoring for these adverse events will involve clinical examination blood sample analysis including parameters such as Hb CRP and leukocytes and radiologic imaging such as CT scans and MRI
Blood samples for DNA genotyping Genomics methylation Epigenetics and RNA sequencing Transcriptomics will be collected at baseline 6- and 12-months FU from participants who have consented to participate in the genetic analysis component of the study Participation is optional Participants who do not wish to participate in the genetic research may still participate in the study
The researchers will also at baseline 6- and 12 months measure a panel of 40 cytokines by duplicate serum analysis with a 40-plex Pro Human Chemokine multi-bead assay Samples that can be used to analyze suspected molecular biomarkers in the future will also be collected
For all participants throughout the study the investigator and study site personnel will collect data about healthcare resource utilization associated with medical encounters The cost-benefit analysis of LIF versus MRE will be assessed by QUALYs derived from EQ-5D-5L and hospital and community treatment costs The following data will be collected
LIF Time in theatre duration of surgery blood loss and transfusions number of surgeons anesthesiologists and nurses implant costs length of sick leave use of non-operative treatment ie physiotherapy rehabilitation additional visits to the GP additional follow-ups including imaging outside the study protocol
MRE Medical consultations at the general practitioner or other primary care treatment additional diagnostic tests eg X-ray MRI CT laboratory tests medications eg pain relievers muscle relaxants anti-inflammatories antidepressants time spent at treatment facilities staffing costs travel expenses for patients traveling to rehabilitation institution for every treatment day or session accommodation costs for patients staying at the rehabilitation institution during the treatment period and sick leave
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