Clinical trial NCT01011816: Treatment of Symptomatic Lumbar Internal Disc Disruption (IDD) With the Biostat® System
Official title: A Multicenter, Randomized, Blinded, Saline-Controlled Trial of Resorbable Biologic Disc Augmentation for Treatment of Symptomatic Lumbar Internal Disc Disruption (IDD) With the Biostat® System
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Back Pain
Chronic Low Back Pain
Internal Disc Disruption
Degenerative Disc Disease
Keywords: intervertebral disk
Lead sponsor: Spinal Restoration, Inc.
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Subject Composite Success
timeFrame: 26 weeks
Secondary outcomes:
measure: Visual Analog Scale for Low Back Pain
timeFrame: 26-weeks
measure: Roland-Morris Disability Questionnaire Score
timeFrame: 26-weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC
state: Alabama
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Chula Vista
country: United States
facility: Pain Control Associates of San Diego
state: California
city: Napa
country: United States
facility: Napa Pain Institute
state: California
city: San Francisco
country: United States
facility: California Spine Diagnostics
state: California
city: Santa Monica
country: United States
facility: The Spine Institute
state: California
city: Merritt Island
country: United States
facility: The Pain Institute, Inc
state: Florida
city: Bloomington
country: United States
facility: Millennium Pain Center
state: Illinois
city: Baltimore
country: United States
facility: The Spine Center
state: Maryland
city: Edina
country: United States
facility: Medical Advanced Pain Specialists Applied Research Center
state: Minnesota
city: Flowood
country: United States
facility: NewSouth NeuroSpine Pain Center
state: Mississippi
city: Charlotte
country: United States
facility: OrthoCarolina Spine Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: New Albany
country: United States
facility: OrthoNeuro, Inc.
state: Ohio
city: Altoona
country: United States
facility: Allegheny Pain Management
state: Pennsylvania
city: York
country: United States
facility: Orthopaedic & Spine Specialists
state: Pennsylvania
city: Tyler
country: United States
facility: Spine Specialists PA
state: Texas
city: Richmond
country: United States
facility: Virginia Spine Research Institute
state: Virginia
city: Virginia Beach
country: United States
facility: Advanced Pain Management
state: Virginia
city: Bellingham
country: United States
facility: Bellingham Spine Pain Specialists PS
state: Washington
Study officials:
affiliation: Spine Specialists PA
name: Kevin J Pauza, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yin W, Pauza K, Olan WJ, Doerzbacher JF, Thorne KJ. Intradiscal injection of fibrin sealant for the treatment of symptomatic lumbar internal disc disruption: results of a prospective multicenter pilot study with 24-month follow-up. Pain Med. 2014 Jan;15(1):16-31. doi: 10.1111/pme.12249. Epub 2013 Oct 23.
citation: Buser Z, Keulling F, Jane L, Liebenberg E, Tang J, Thorne K, Coughlin D, Lotz J. Fibrin injection stimulates early disc healing in the porcine model [NASS Abstract 199]. Spine Journal 9:105S, 2009.
citation: Buser Z, Kuelling F, Liu J, Liebenberg E, Thorne KJ, Coughlin D, Lotz JC. Biological and biomechanical effects of fibrin injection into porcine intervertebral discs. Spine (Phila Pa 1976). 2011 Aug 15;36(18):E1201-9. doi: 10.1097/BRS.0b013e31820566b2.
citation: Pauza K, Yin W, Olan W, Doerzbacher JF. BIOSTAT BIOLOGX(R) intradiscal fibrin sealant used for treatment of chronic low back pain caused by lumbar disc disruption: results of a 12 month, prospective multicenter pilot study. Spine Arthroplasty Society Meeting, April 27-30, 2010; New Orleans, LA. Abstract 248.
citation: Yin W, Pauza K, Olan W, Doerzbacher JF. Long-term outcomes from a prospective, multicenter investigational device exemption (IDE) pilot study of intradiscal fibrin sealant for the treatment of discogenic pain [ISIS Abstract]. Pain Medicine 12:1446-1447, 2011
citation: Buser Z, Liu J, Thorne KJ, Coughlin D, Lotz JC. Inflammatory response of intervertebral disc cells is reduced by fibrin sealant scaffold in vitro. J Tissue Eng Regen Med. 2014 Jan;8(1):77-84. doi: 10.1002/term.1503. Epub 2012 May 18.