Clinical Trial: A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Study of INFUSE Bone Graft (Recombinant Human Bone Morphogenetic Protein-2/Absorbable Collagen Sponge) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis 1 (NF1)

Brief Summary: The current study proposes adding BMP-2 (INFUSE), an anabolic agent, at the surgical site of TPA repair in children with NF1, compared to a control group of patients treated surgically without BMP-2. The following Specific Aims will be addressed: 1) to determine if use of an osteogenic agent (BMP-2) at the time of surgical repair of TPA in NF1 patients will result in improved bone healing; 2) to document safety of BMP-2 in a pediatric NF1 population; and 3) to collect, process, and preserve biologic specimens at the time of surgery for future studies.

Detailed Summary: A randomized study will be performed by a multi-center group of the NF Consortium. A total of 54 patients will be randomized for treatment with or without INFUSE Bone Graft at the time of surgical repair. For all patients, a standard surgical procedure will be used, including: resection of pseudarthrosis tissue; placement of a rigid intramedullary rod; and placement of autogenous bone graft from iliac crest. For patients in the BMP group, the INFUSE device containing BMP-2 will in addition be applied intraoperatively to the osteotomy site. Fracture union will be determined by scoring of radiographs (RUST score) for cortical bone fusion and callus formation at the osteotomy site. RUST score at 12 months post-surgery will be the primary outcome measure to determine efficacy. Secondary measures will include determination of time to healing (months); quality of life measures; functional walking measures; and incidence of refracture after surgery. This study, once successfully completed, will determine if use of INFUSE Bone Graft improves healing of tibial pseudarthrosis in NF1 and will document safety issues. Regardless of results, the better performing of the two groups (control or BMP) will be able to serve as a much-needed control arm for future studies of additional targeted therapeutic agents for NF1-related bone disease. An international working group of orthopaedic surgeons and NF specialists has been formed and is committed to successful completion of this trial.
Sponsor: University of Alabama at Birmingham

Current Primary Outcome: RUST score [ Time Frame: 12 mos post surgery. The score at 12 mos post surgery will be used to determine success of healing ]

Radiographic Union Score of Tibia (RUST) calculated from X-rays.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Average time to healing in months [ Time Frame: X-rays obtained at 3, 6, 9, and 12 mos. post-surgery ]
    Time to healing is determined by RUST scores calculated at 3 month intervals after surgery. A score of 9/12 is considered to be complete healing.
  • Refracture rate [ Time Frame: 12 months post-surgery ]
    Numbers of patients with refracture within 1 year after surgery.
  • Long-term refracture [ Time Frame: annually, up to 10 years post-surgery ]
    Numbers of patients with refracture over long-term follow up of up to 10 years.
  • Ten Meter Timed Walk [ Time Frame: 6 and 12 mos. after surgery. ]
    Time (seconds) to perform the Ten Meter Timed Walk.
  • Pain intensity [ Time Frame: measured at post-op visits at 6 weeks, 3 mos, 6 mos, and 12 mos after surgery ]
    Pain intensity as assessed by the patient with the Faces Pain Scale-Revised (FPS-R).
  • Quality of life score [ Time Frame: 6 and 12 mos. after surgery ]
    QOL measured by the Pediatric Outcome Data Collection Instrument (PODCI), filled out by patient and parent.
  • Adverse Events [ Time Frame: measured at post-op visits at 6 weeks, 3 mos, 6 mos, and 12 mos after surgery ]
    Numbers of participants with treatment-related adverse events as assessed by CTCAE v4.0.


Original Secondary Outcome: Same as current

Information By: University of Alabama at Birmingham

Dates:
Date Received: March 7, 2016
Date Started: March 2016
Date Completion: December 2021
Last Updated: May 3, 2017
Last Verified: May 2017