Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06356844 |
| Other study ID # |
27.02.2023-E.142568 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 27, 2024 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Bezmialem Vakif University |
| Contact |
zübeyde özdemir |
| Phone |
+90 2125232288 |
| Email |
etikkurul[@]bezmialem.edu.tr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Brief Summary: Inflammatory back pain is a chronic condition localized in the axial spine and
sacroiliac joints.1 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
ineffective.2 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 surgery.3,4 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: n=25) will
receive epidural steroids, while the study group (Group R: n=25) 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 protruded/extruded 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.
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 pain.5 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 macrophages.6,7 Cytokines, as regulatory proteins
acting as pro-inflammatory biomarkers, modulate the inflammatory response of all immune
system cells during instances of inflammation.8 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 individuals.9
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. 9,10 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, and/or 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
kg/m²), 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 4L/min 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 0.50 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 Student's
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 0.05.
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
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(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
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inflammation and pain. Trends Neurosci. 2011 Nov;34(11):599-609. PMID: 21963090; PMCID:
PMC3200462.
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