Treatment of Symptomatic Lumbar Internal Disc Disruption (IDD) With the Biostat® System

Back Pain Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01011816
• Other study ID #: SR-BX01-2007
• Status: Terminated
• Phase: Phase 3
• First received: November 9, 2009
• Last updated: May 5, 2014
• Start date: March 2010
• Est. completion date: May 2013

Study information

• Verified date: May 2014
• Source: Spinal Restoration, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 220
• Est. completion date: May 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Back Pain
• Chronic Low Back Pain
• Degenerative Disc Disease
• Internal Disc Disruption
• Intervertebral Disc Degeneration
• Low Back Pain

Intervention

Biological:
• 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

Drug:
• Saline
One injection of up to 4 mL of saline using the Biostat Delivery Device

Locations

Country	Name	City	State
United States	Allegheny Pain Management	Altoona	Pennsylvania
United States	The Spine Center	Baltimore	Maryland
United States	Bellingham Spine Pain Specialists PS	Bellingham	Washington
United States	Alabama Clinical Therapeutics, LLC	Birmingham	Alabama
United States	Millennium Pain Center	Bloomington	Illinois
United States	OrthoCarolina Spine Center	Charlotte	North Carolina
United States	Pain Control Associates of San Diego	Chula Vista	California
United States	Cleveland Clinic	Cleveland	Ohio
United States	Medical Advanced Pain Specialists Applied Research Center	Edina	Minnesota
United States	NewSouth NeuroSpine Pain Center	Flowood	Mississippi
United States	The Pain Institute, Inc	Merritt Island	Florida
United States	Napa Pain Institute	Napa	California
United States	OrthoNeuro, Inc.	New Albany	Ohio
United States	HOPE Research Institute	Phoenix	Arizona
United States	Virginia Spine Research Institute	Richmond	Virginia
United States	California Spine Diagnostics	San Francisco	California
United States	The Spine Institute	Santa Monica	California
United States	Spine Specialists PA	Tyler	Texas
United States	Advanced Pain Management	Virginia Beach	Virginia
United States	Orthopaedic & Spine Specialists	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Spinal Restoration, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

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.

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. — View 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. — View 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.

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	26 weeks	Yes
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.	26-weeks	No
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.	26-weeks	No