The Lumbar Interbody Fusion vs. Multidisciplinary Rehabilitation (LIFEHAB) Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 202
- 试验地点
- 5
- 主要终点
- Oswestry Disability Index (ODI): Change in percent
研究概览
简要总结
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
详细描述
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 (e.g., 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Outcomes assessors will not have access to information about participants' allocated treatment groups (lumbar interbody fusion or multidisciplinary rehabilitation)
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and non-pregnant female patients between 20 and 65 years of age with persistent low back pain of at least one year's duration at inclusion
- •Received non-operative treatment in line with national [50] and international [49] guidelines, including at least self-management, exercise, and physical therapy, without satisfactory effect before study enrolment
- •Back-related disability: ODI 30 - 60 points at baseline
- •Back pain > leg pain
- •One- or two-level disc degeneration between L2 and sacrum with any of the following:
- •High-intensity zone (HiZ)
- •Modic changes
- •Severe disc height reduction exceeding 50% of the cranial disc
排除标准
- •Multilevel disc degeneration requiring intervention beyond two levels
- •Spondylolysis or lytic spondylolisthesis
- •History of previous spondylodiscitis
- •Previous lumbar fusion surgery
- •Scoliosis >20 degrees
- •Signs of a vertebral fracture at the planned level of fusion or its adjacent levels
- •Active smokers
- •Unlikely to adhere to treatment or complete follow-up (e.g., ongoing serious psychiatric disease, drug abuse, plans to move outside the catchment areas of the trial centers)
- •Significant nerve root compression assessed by MRI and clinical examination
- •Not understanding the Norwegian language.
- •Generalized myalgia, including history or signs of fibromyalgia and myalgic encephalitis
- •Contraindications to MRI (e.g., cardiac pacemaker electrodes, metal implants in the eye or brain, claustrophobia).
- •Active cancer
- •Disabling chronic neurological disease (e.g., Parkinson's disease, ALS, MS)
- •Disabling osteoarthritis of the hip or knee (Kellgren & Lawrence grade III or higher)
- •Daily use of morphine equivalents ≥ 60mg or regular use of morphine-containing pain patches
- •Decline specific treatment arm
研究组 & 干预措施
Lumbar Interbody Fusion (LIF)
Per center standard, the LIF procedure is done in one or two levels between the second lumbar vertebra and sacrum, as a transforaminal lumbar interbody fusion (TLIF) or anterior lumbar interbody fusion (ALIF). Stabilization with screws is mandatory. TLIF employs bilateral pedicle screws. ALIF uses either pedicle or intra-device screws.
At least one surgeon must be proficient in both procedure and implants. TLIF requires visual aids (microscope/magnifying glasses) for precise disc preparation. In the TLIF procedure, surgeons will maximize bone implantation into the disc space, anteriorly, posteriorly, or both.
If the disc space is too narrow for an interbody device, autologous bone grafting into the disc space (local, spongious, or both) with posterior pedicle screw fixation is accepted. Optional posterolateral autologous bone grafting is allowed, but no substitutes or osteoinductive proteins (e.g., BMP). Surgical drain is optional.
干预措施: Lumbar Interbody Fusion (Procedure)
Multidisciplinary Rehabilitation
Rehabilitation, guided by a team of experienced specialists in physical medicine and rehabilitation and physiotherapists trained in cognitive therapy, will direct the multidisciplinary treatment. Patients receive 2.5-5 hour sessions 2-4 days weekly over 3-5 weeks. Standardization is maintained through pre-study training for providers, including seminars, podcasts, videos, and lectures.
Individual screenings start the process, leading to focused discussions on thoughts, feelings, behaviour, and physical symptoms. A plan for the rehabilitation process with clearly defined individual goals will be worked out and revised every week. The three components described within the framework of cognitive functional therapy will be a template for the implementation of the functional and physical rehabilitation, involving pain understanding, exposure with control, and lifestyle changes like physical activity, sleep, diet, stress management, and social engagement.
干预措施: Multidisciplinary rehabilitation (Behavioral)
结局指标
主要结局
Oswestry Disability Index (ODI): Change in percent
时间窗: At one-year follow-up
Improvement in the ODI score of a minimum of 30% from baseline. The ODI questionnaire examines the level of disability based on 10 everyday activities of daily living. Each item consists of 6 statements which are scored from 0 to 5, with 0 indicating the least disability and 5 the highest level of disability. The total score is calculated as a percentage, with 0% indicating no disability and 100% indicating the highest level of disability.
次要结局
- Oswestry Disability Index (ODI): Dichotomized(At one-year follow-up)
- MRI spectroscopy biomarkers and molecular biomarkers(At baseline, 6-, and 12 months follow-up)
- Oswestry Disability Index (ODI): Continuous(At one-year follow-up)
- Numeric Rating Scale leg pain (NRS leg pain)(At one-year follow-up)
- Global perceived effect (GPE)(At one-year follow-up)
- EuroQol-5 dimensions-5 levels (EQ-5D-5L)(At one-year follow-up)
- Numeric Rating Scale back pain (NRS back pain)(At one-year follow-up)
- Fear Avoidance Beliefs Questionnaire (FABQ)(At one-year follow-up)
- Hopkins Symptom Check List (HSCL-25)(At one-year follow-up)
- Pain Catastrophizing Scale (PCS)(At one-year follow-up)
- Adverse Events of special interest (AESI) and Serious Adverse Events (SAEs)(During study period (two years))
- Occupational status and return to work(At one-year follow-up)
- ActivePAL accelerometer and sleep diary(At one-year follow-up)
- Molecular biomarkers: Change in ODI from baseline (continuous variable)(At one-year follow-up)
- Molecular biomarkers: Change in NRS leg pain from baseline (continuous variable)(At one-year follow-up)
- Cost-effectiveness: EQ-5D-5L(At one-year follow-up)
- Cost-effectiveness: Hospital costs(At one-year follow-up)
- Cost-effectiveness: Co-interventions (pharmacological and non-pharmacological)(At one-year follow-up)
- Cost-effectiveness: Community costs including sick leave(At one-year follow-up)
- Molecular biomarkers: Change in NRS back pain from baseline (continuous variable)(At one-year follow-up)
- Molecular biomarkers: Improvement in the ODI score of a minimum 30% from baseline(At one-year follow-up)
- MRI spectroscopy biomarkers: Change in ODI from baseline (continuous variable)(At one-year follow-up)
- MRI spectroscopy biomarkers: Change in NRS back pain from baseline (continuous variable)(At one-year follow-up)
- MRI spectroscopy biomarkers: Change in NRS leg pain from baseline (continuous variable)(At one-year follow-up)
- MRI spectroscopy biomarkers: Improvement in the ODI score of a minimum 30% from baseline(At one-year follow-up)
研究者
Kjersti Storheim
Senior researcher, professor
Oslo University Hospital