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Intradiscal rhGDF-5 Phase I/II Clinical Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
DePuy Spine
ClinicalTrials.gov Identifier:
NCT00813813
First received: December 22, 2008
Last updated: January 26, 2016
Last verified: January 2016
  Purpose
Study to show the effectiveness and safety of a single injection of rhGDF5 into a degenerating single spinal disc in treating lumbar level degenerative disc disease

Condition Intervention Phase
Degenerative Disc Disease
Drug: Intradiscal rhGDF-5
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II, Multicenter, Open-label, Single Administration, Dose Finding, Clinical Trial to Evaluate the Safety and Tolerability of Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration

Resource links provided by NLM:


Further study details as provided by DePuy Spine:

Primary Outcome Measures:
  • Neurological Assessment for Motor Function and Reflexes/Sensory [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

    Neurological Assessment for Motor Function and Reflexes/Sensory- Number of patients with Clinically Significant Abnormal results at 12 months.

    For Motor Function, Clinically Significant Abnormal results are determined by the surgeon investigator and are further classified by grade: 0= No Movement, 1= Flicker/trace of contraction, 2=Active movement when gravity removed, 3= Active movement against gravity, 4= Active Movement against gravity and resistance.

    For Reflexes/Sensory, Clinically Significant Abnormal results are determined by the surgeon investigator and are based on exams of the Knee, Ankle, L3-L5 Dermatone, and S1 Dermatome. Tension signs are evaluated with a straight leg raise to determine at which point, if any, sciatic pain occurs.


  • Treatment Emergent Adverse Events- Relationship to Study Drug [ Time Frame: Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up ] [ Designated as safety issue: Yes ]
    Number of patients with Treatment Emergent Adverse Events that were designated as related or possibly related to Study Drug.


Secondary Outcome Measures:
  • Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The Oswestry Disability Index (ODI) is a 10-category (Pain Intensity, Personal Care, Lifting, Walking, Sitting, Standing, Sleeping, Sex Life, Social Life, Traveling) disability measurement scale with a graded response from 0 to 5, with 0 being the best score (no impairment) to 5 being the worst score (significant impairment). ODI score for a subject is calculated by adding the scores and converting the score to a 100 point scale.

  • Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The Visual Analog Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 10=10cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their back.

  • Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component - PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health).

  • Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component - PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health).


Enrollment: 32
Study Start Date: June 2008
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intradiscal rhGDF-5
The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. In vitro experiments have shown that rhGDF-5 can stimulate gene expression and synthesis of the extracellular matrix proteins type II collagen and aggrecan. In vivo experiments in rabbit models of disc degeneration have shown that intradiscal injections of rhGDF-5 can stimulate an increase in disc height and hydration.
Drug: Intradiscal rhGDF-5
The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. In vitro experiments have shown that rhGDF-5 can stimulate gene expression and synthesis of the extracellular matrix proteins type II collagen and aggrecan. In vivo experiments in rabbit models of disc degeneration have shown that intradiscal injections of rhGDF-5 can stimulate an increase in disc height and hydration.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Persistent low back pain, with at least 3 months of non-surgical therapy, at one symptomatic lumbar level (L3/L4 to L5/S1) as confirmed using a standardized discography protocol
  2. Oswestry Disability Index of 30 or greater
  3. Low back pain score greater than or equal to 4 cm as measured by VAS, at Visit 1 baseline and on day of treatment to confirm eligibility prior to administration

Exclusion Criteria:

  1. Persons unable to have a discogram, CT or an MRI
  2. Abnormal neurological exam at baseline (e.g., radiculopathy)
  3. Radicular pain
  4. Leak of contrast agent during the discogram, into the epidural space (does not include leak of contrast agent along the needle track)
  5. MRI findings demonstrate any of the following:· Suspected disc appears normal· >50% decrease in disc height· Modic changes, and/or· Presence of osteophytes or significant facet arthrosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00813813

Locations
United States, California
Spine Institute
Santa Monica, California, United States, 90404
United States, Colorado
Durango Orthopedic Associates/Spine Colorado
Durango, Colorado, United States, 81301
United States, Georgia
Drug Studies America
Marietta, Georgia, United States, 30060
United States, Illinois
Rehabilitation Institute of Chicago
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Ohio
Riverhills Healthcare, Inc.
Cincinnati, Ohio, United States, 45242
United States, Texas
TBI Clinical Research, LLC
Plano, Texas, United States, 75093
United States, Virginia
Virginia Commonwealth University Spine Center
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
DePuy Spine
Investigators
Principal Investigator: James Rathmell, MD Massachusetts General Hospital
Principal Investigator: Richard Guyer, MD Texas Back Institute
Principal Investigator: Marvin Tark, MD Drug Study America
Principal Investigator: Jim Youssef, MD Durango Orthopedic Associates/Spine Colorado
Principal Investigator: Norman Harden, MD Rehabilitation Institute of Chicago
Principal Investigator: Jonathan Borden, MD Riverhills Healthcare, Inc.
Principal Investigator: Yaoming Gu, MD Virginia Commonwealth University
  More Information

Responsible Party: DePuy Spine
ClinicalTrials.gov Identifier: NCT00813813     History of Changes
Other Study ID Numbers: 07-Intradiscal rhGDF-5-01 
Study First Received: December 22, 2008
Results First Received: December 18, 2015
Last Updated: January 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Intervertebral Disc Degeneration
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on December 09, 2016