Back Pain, Chronic Low Back Pain, Degenerative Disc Disease, Internal Disc Disruption
Conditions
Keywords
intervertebral disk
Brief summary
The purpose of this investigation is to establish the safety and efficacy of the Biostat System when used for treatment of chronic low back (lumbar) pain due to symptomatic internal disc disruptions (IDD) by comparing safety and efficacy outcome measures between one group receiving BIOSTAT BIOLOGX® Fibrin Sealant through the Biostat® Delivery Device and another group receiving a preservative-free normal saline control delivered with the Biostat Delivery Device.
Detailed description
The Biostat System is a combination product combining a resorbable biologic product with a delivery device system used to prepare and insert the biologic material into a lumbar intervertebral disc. Symptomatic IDD is defined as a painful disruption of the internal architecture of a lumbar intervertebral disc, which appears as fissures, cracks or tears within the internal structures of the disc. Pain arising from a lumbar disc may not only be perceived as pain located in the low back (axial pain) but also as somatic referred pain involving the posterior hips, buttocks, lateral hips, groin, or posterior thighs. The diagnosis of symptomatic IDD cannot currently be made on the basis of imaging studies, physical examination, or symptoms alone, and is best established with meticulously conducted disc provocation studies (provocation discography) that include pressure manometry and identification of an adjacent normal disc. This treatment and study are not designed for patients exhibiting other potential sources of chronic low back pain such as more advanced degenerative disc disease with significant loss of disc height (\>33%), spinal stenosis, or spondylolisthesis (see Eligibility Criteria).
Interventions
BIOLOGICALBIOSTAT BIOLOGX
One injection of up to 4 mL of BIOSTAT BIOLOGX Fibrin Sealant into a single lumbar intervertebral disc using the Biostat Delivery Device
DRUGSaline
One injection of up to 4 mL of saline using the Biostat Delivery Device
Sponsors
Spinal Restoration, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older and skeletally mature. * Voluntarily signs the subject informed consent form and agrees to the release of medical information for purposes of this study (HIPAA authorization). * Physically and mentally able to comply with the protocol, including ability to read and complete required forms, and willing and able to adhere to the follow-up requirements of the protocol. * Chronic low back pain for at least 6 months. * Pretreatment baseline low back pain of at least 40 mm on a 100 mm visual analog scale. * Pretreatment baseline Roland-Morris Disability Questionnaire score of at least 9 on the 24-point questionnaire. * Leg pain, if present, is of nonradicular origin, i.e., not due to stimulation of nerve roots or dorsal root ganglion of a spinal nerve by compressive forces. * Leg pain, if present, does not extend below the knee and is no greater than 50% of low back pain as measured on a visual analog scale. If bilateral leg pain, the worst leg pain is no greater than 50% of low back pain. * Low back pain unresponsive to at least 3 months of nonoperative care, which may include bed rest, antiinflammatory and analgesic medications, chiropractic manipulations, acupuncture, massage, physical therapy or home-directed lumbar exercise program. * Diagnostic medial branch block or facet joint injection between 18 months and 2 weeks prior to the study procedure indicates no facet joint involvement. * Diagnosis of symptomatic lumbar (L1-L2 - L5-S1) internal disc disruption (IDD), which requires confirmation of discogenic pain at one or two contiguous levels through positive provocation discography performed between 18 months and 2 weeks prior to the study procedure using pressure manometry and identification of an adjacent nonpainful disc. The disc provocation studies must precisely demonstrate concordant pain (\<50 psi above opening pressure) and must demonstrate a fissure(s) in the outer one-third of the posterior or lateral anulus.
Exclusion criteria
* Cauda equina syndrome. * Active malignancy or tumor as source of symptoms. * Current infection or prior history of spinal infection (e.g., discitis, septic arthritis, epidural abscess) or an active systemic infection. * Previous lumbar spine surgery. * Evidence of prior lumbar vertebral body fracture. * Disc bulge/protrusion or focal herniation at the symptomatic level(s) \> 4 mm. * Presence of disc extrusion or sequestration. * Leg pain is greater than 50% of low back pain as measured on a visual analog scale. * Leg pain that extends below the knee. * Lumbar intervertebral foramen stenosis at the affected level(s) resulting in significant spinal nerve root compression (effacement of the majority of periganglion fat and loss of CSF signal around the nerve rootlets). * Symptomatic central vertebral canal stenosis or absolute sagittal vertebral canal diameter \< 9mm. * Loss of disc space height at the symptomatic level(s) greater than one-third of an adjacent normal disc (or of the expected height in the case of an L5-S1 disc). * Spondylolisthesis (\> Grade 1) with or without spondylolysis at the symptomatic level(s). * Lumbar spondylitis or other undifferentiated spondyloarthropathy. * Dynamic instability at the symptomatic level(s) on lumbar flexion-extension radiographs indicated by \>4.5 mm of translation or angular motion \>15° at L1-L2, L2-L3, or L3-L4; \>20° at L4-L5; or \>25° at L5-S1. * Diagnostic medial branch block or facet joint injection indicate facet joint involvement. * Diagnostic sacroiliac injection indicates sacroiliac joint involvement for those patients with pain in the sacral region. * Sustained relief (\>3 months) of low back pain obtained with epidural injection of corticosteroids. * Symptomatic involvement of more than two lumbar disc levels determined from discography. * Neurological examination shows findings of radiculopathy or a significant underlying neurological condition (motor strength \<4; sensory assessment abnormal; or reflexes absent or hyperactive with clonus). * Prior thermal intradiscal procedure (e.g., intradiscal electrothermal therapy, intradiscal radiofrequency thermocoagulation). * Any lumbar intradiscal injection procedure other than discography (e.g., injection of corticosteroids, methylene blue, dextrose, or glucosamine and chondroitin sulfate). * Significant systemic disease, including unstable angina, autoimmune disease, rheumatoid arthritis, and muscular dystrophy. * Congenital or acquired coagulopathy or thrombocytopenia; or currently taking anticoagulant, antineoplastic, antiplatelet, or thrombocytopenia-inducing medications; or undergoing radiation therapy. * History of unexplained, easy, or persistent bruising or bleeding, bleeding from the gums, or bleeding problems experienced in previous surgical procedures. * Aspirin or aspirin-containing medication taken ≤ 7 days prior to the procedure. * Known or suspected hypersensitivity or allergy to drugs or components of the fibrin sealant (fibrinogen, thrombin, aprotinin, CaCl2) used in the procedure. * History of, or current psychiatric or psychological condition, or substance or alcohol abuse that would potentially interfere with the subject's participation in the study. * Ongoing or previous participation in another drug or device clinical study within the previous 2 months. * Subject known to be pregnant or nursing at time of enrollment or with plans to become pregnant within the planned length of follow-up. * Body habitus precludes adequate fluoroscopic visualization for the procedure or the procedure is physically impossible using the device. * Concomitant conditions requiring daily oral steroid use for more than 30 days in the preceding 90 days. * Pending litigation against a health care professional, except where required by the insurer as a condition of coverage, personal injury compensation or litigation claims. * Prisoner or active military personnel who would not be available for follow-up. * Presence of ferromagnetic implants that would disallow MRI of the symptomatic disc(s). * Active or pending workers' compensation claims.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject Composite Success | 26 weeks | Subject success based on a composite of minimum 30% decrease in low back pain, 30% improvement in function, maintenance of neurological status, no secondary interventions, and no serious adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale for Low Back Pain | 26-weeks | Percent of subjects achieving a minimum 30% decrease in pain from baseline. The visual analog scale is a horizontal 100 mm line anchored on the left with the words No Pain and on the right with the words Worst Possible Pain. Scores were obtained by measuring the distance in millimeters from the left origin of the line (0) to the point indicated with a slash placed by the subject to indicate the subject's level of low back pain experienced over the last week. |
| Roland-Morris Disability Questionnaire Score | 26-weeks | Percent of subjects achieving a minimum 30% decrease in Roland-Morris Disability Questionnaire score The Roland-Morris Disability Questionnaire is a widely studied and frequently used instrument for the assessment of function and disability related to low back pain. The questionnaire consists of 24 statements related to how a subject's back condition affects various activities of daily living. Subjects marked whether the statement either applied to them or did not apply at the time they responded to the statements. The score is the total number of questions with which the subject agreed. A higher score indicates less function and greater disability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIOSTAT BIOLOGX One injection of up to 4 mL of BIOSTAT BIOLOGX Fibrin Sealant into a single lumbar intervertebral disc using the Biostat Delivery Device | 164 |
| Saline One injection of up to 4 mL of saline solution into a single lumbar intervertebral disc using the Biostat Delivery Device | 56 |
| Total | 220 |
Baseline characteristics
| Characteristic | Saline | BIOSTAT BIOLOGX | Total |
|---|---|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 11.4 | 39.7 years STANDARD_DEVIATION 10.7 | 40.2 years STANDARD_DEVIATION 10.9 |
| Age, Customized ≥18-≤29 years | 11 participants | 30 participants | 41 participants |
| Age, Customized ≥30-≤39 years | 12 participants | 50 participants | 62 participants |
| Age, Customized ≥40-≤49 years | 20 participants | 51 participants | 71 participants |
| Age, Customized ≥50-≤59 years | 9 participants | 28 participants | 37 participants |
| Age, Customized ≥60 years | 4 participants | 5 participants | 9 participants |
| Baseline Opioid Medication for Back Pain No | 19 participants | 55 participants | 74 participants |
| Baseline Opioid Medication for Back Pain Yes | 37 participants | 109 participants | 146 participants |
| BMI | 27.5 kg/m^2 STANDARD_DEVIATION 5.6 | 28.0 kg/m^2 STANDARD_DEVIATION 6.1 | 27.9 kg/m^2 STANDARD_DEVIATION 5.9 |
| Currently Employed No | 22 participants | 65 participants | 87 participants |
| Currently Employed No Response | 0 participants | 3 participants | 3 participants |
| Currently Employed Yes | 34 participants | 96 participants | 130 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 8 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 156 Participants | 207 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| History Left Leg Pain 1 - <2 years | 2 participants | 7 participants | 9 participants |
| History Left Leg Pain <1 year | 6 participants | 11 participants | 17 participants |
| History Left Leg Pain 2 - <3 years | 7 participants | 14 participants | 21 participants |
| History Left Leg Pain 3 - <4 years | 1 participants | 3 participants | 4 participants |
| History Left Leg Pain >=4years | 7 participants | 19 participants | 26 participants |
| History Left Leg Pain None | 33 participants | 110 participants | 143 participants |
| History Low Back Pain 0.5 - 1 year | 3 participants | 7 participants | 10 participants |
| History Low Back Pain 10 - <20 years | 12 participants | 32 participants | 44 participants |
| History Low Back Pain 1 - <5 years | 24 participants | 76 participants | 100 participants |
| History Low Back Pain >=20 years | 8 participants | 8 participants | 16 participants |
| History Low Back Pain 5 - <10 years | 9 participants | 41 participants | 50 participants |
| History Right Leg Pain 1 - <2 years | 2 participants | 11 participants | 13 participants |
| History Right Leg Pain <1 year | 3 participants | 8 participants | 11 participants |
| History Right Leg Pain 2 - <3 years | 5 participants | 11 participants | 16 participants |
| History Right Leg Pain 3 - <4 years | 0 participants | 2 participants | 2 participants |
| History Right Leg Pain >=4 years | 6 participants | 14 participants | 20 participants |
| History Right Leg Pain None | 40 participants | 118 participants | 158 participants |
| Injection Volume | 3.3 ml STANDARD_DEVIATION 0.8 | 2.8 ml STANDARD_DEVIATION 0.9 | 2.9 ml STANDARD_DEVIATION 0.9 |
| Lumbar Level Treated L3/L4 | 8 participants | 12 participants | 20 participants |
| Lumbar Level Treated L4/L5 | 11 participants | 48 participants | 59 participants |
| Lumbar Level Treated L5/S1 | 37 participants | 104 participants | 141 participants |
| Maximum Injection Pressure | 49.7 psi STANDARD_DEVIATION 25.7 | 83.0 psi STANDARD_DEVIATION 29.3 | 74.6 psi STANDARD_DEVIATION 31.9 |
| Previous Back Surgery Cervical | 1 participants | 3 participants | 4 participants |
| Previous Back Surgery None | 55 participants | 161 participants | 216 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 15 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 52 Participants | 147 Participants | 199 Participants |
| Reason for Stopping Injection Maximum Pressure Reached | 6 participants | 91 participants | 97 participants |
| Reason for Stopping Injection Other [investigator discretion; saline backflow] | 3 participants | 1 participants | 4 participants |
| Reason for Stopping Injection Subject Discomfort | 2 participants | 4 participants | 6 participants |
| Reason for Stopping Injection Total Available Volume Delivered | 45 participants | 68 participants | 113 participants |
| Sex: Female, Male Female | 32 Participants | 83 Participants | 115 Participants |
| Sex: Female, Male Male | 24 Participants | 81 Participants | 105 Participants |
| Smoking Status Current | 16 participants | 28 participants | 44 participants |
| Smoking Status Never | 21 participants | 90 participants | 111 participants |
| Smoking Status Previous | 19 participants | 46 participants | 65 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 49 / 164 | 11 / 56 |
| serious Total, serious adverse events | 22 / 164 | 7 / 56 |
Outcome results
Primary
Subject Composite Success
Subject success based on a composite of minimum 30% decrease in low back pain, 30% improvement in function, maintenance of neurological status, no secondary interventions, and no serious adverse events.
Time frame: 26 weeks
Population: All subjects adjudicated as a success or failure. Missed 26-week visit counted as failure (7 BIOSTAT BIOLOGX; 2 Saline). Unblinded subjects counted as failures (2 BIOSTAT BIOLOGX).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIOSTAT BIOLOGX | Subject Composite Success | 33.5 percentage of subjects |
| Saline | Subject Composite Success | 39.3 percentage of subjects |
Comparison: Null: No differenc between the percent success of Saline and BIOSTAT BIOLOGXp-value: 0.52Fisher Exact
Secondary
Roland-Morris Disability Questionnaire Score
Percent of subjects achieving a minimum 30% decrease in Roland-Morris Disability Questionnaire score The Roland-Morris Disability Questionnaire is a widely studied and frequently used instrument for the assessment of function and disability related to low back pain. The questionnaire consists of 24 statements related to how a subject's back condition affects various activities of daily living. Subjects marked whether the statement either applied to them or did not apply at the time they responded to the statements. The score is the total number of questions with which the subject agreed. A higher score indicates less function and greater disability.
Time frame: 26-weeks
Population: All subjects assigned as success or failure. Missed 26-week visit counted as failure (7 BIOSTAT BIOLOGX; 2 Saline). Unblinded subjects counted as failures (2 BIOSTAT BIOLOGX).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIOSTAT BIOLOGX | Roland-Morris Disability Questionnaire Score | 52.4 percentage of subjects |
| Saline | Roland-Morris Disability Questionnaire Score | 50.0 percentage of subjects |
Secondary
Visual Analog Scale for Low Back Pain
Percent of subjects achieving a minimum 30% decrease in pain from baseline. The visual analog scale is a horizontal 100 mm line anchored on the left with the words No Pain and on the right with the words Worst Possible Pain. Scores were obtained by measuring the distance in millimeters from the left origin of the line (0) to the point indicated with a slash placed by the subject to indicate the subject's level of low back pain experienced over the last week.
Time frame: 26-weeks
Population: All subjects assigned success or failure. Missed 26-week visit counted as failure (7 BIOSTAT BIOLOGX; 2 Saline). Unblinded subjects counted as failures (2 BIOSTAT BIOLOGX).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIOSTAT BIOLOGX | Visual Analog Scale for Low Back Pain | 42.1 percentage of subjects |
| Saline | Visual Analog Scale for Low Back Pain | 50.0 percentage of subjects |