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Use of Adipose Derived Regenerative Cells in Bilateral Femoral Head Osteonecrosis

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ClinicalTrials.gov Identifier: NCT03269409
Recruitment Status : Recruiting
First Posted : August 31, 2017
Last Update Posted : July 11, 2018
Sponsor:
Information provided by (Responsible Party):
Rafael J. Sierra, M.D., Mayo Clinic

Brief Summary:
This randomized clinical trial aims to determine if cells from a patient's own adipose tissue is safe and capable of helping regenerate the femoral head in patients with osteonecrosis. The standard of care is known as hip decompression which simply removes dead tissue from the femoral head and creates a new cavity to be filled in by healthy bone. This trial will use hip decompression plus saline injection in one hip and hip decompression supplemented with adipose derived regenerative cells in patients with osteonecrosis in both of their hips.

Condition or disease Intervention/treatment Phase
Osteonecrosis Other: Saline Device: The Celution System (Cytori Therapeutics) Biological: Adipose Derived Regenerative Cells (ADRC) Not Applicable

Detailed Description:

Preclinical and clinical data suggest that ADRC may serve as a safe and efficacious adjuvant agent for the treatment of ON. However, no randomized control study in the United States has formally evaluated safety of ADRC in the setting of ON. Therefore, the primary endeavor of this Phase I pilot study will be to evaluate safety of ADRC for pre-collapse ON of the femoral head.

The Celution System (Cytori Therapeutics, San Diego, USA) for preparation of ADRC from lipoaspirate is currently being evaluated in FDA approved clinical trials including an orthopedic indication (osteoarthritis). In addition, the device has a registration in Europe and Class I approval in Japan. As such, it serves as a known platform that produces a clinical grade product for human use. Other devices on the market process lipoaspirate by either mechanical, washing, or centrifugation methods; however, the remaining components of original adipose tissue are significant and impair the regenerative process. Derivation of relatively pure ADRC has been achieved by few devices and the Cytori Celution System is the only one to our knowledge with a sufficient safety and efficacy track record enabling multiple investigational device exemption (IDE) approvals. The reagent used (Celase®) is of a clinical and pharmacologic grade for use in humans. The production of Celase is free of mammalian products.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double Blind, Phase I, Randomized, Parallel Group Study of Hip Decompression Compared to Hip Decompression Supplemented at the Point of Care With Adipose Derived Regenerative Cells for Bilateral Pre-Collapse Femoral Head Osteonecrosis
Actual Study Start Date : November 15, 2017
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteonecrosis
Drug Information available for: Coal Tar

Arm Intervention/treatment
Sham Comparator: Hip Decompression with saline injection
Subjects will receive standard of care hip decompression along with an injection of 5 ccs of saline.
Other: Saline
5 cc's of saline will be injected after decompression into the hip that does not receive adipose derived regenerative cells.

Experimental: Hip Decompression with ADRC
Subjects in this arm will have Adipose Derived Regenerative Cells (ADRC)harvested through autologous liposuction and processed outside the body using The Celution System (Cytori Therapeutics) before being transplanted into the femoral head after standard of care hip decompression.
Device: The Celution System (Cytori Therapeutics)
The Celution System will be used for the preparation of adipose derived regenerative cells from lipoaspirate. The adipose derived regenerative cells will then be transplanted into the hip, post decompression.

Biological: Adipose Derived Regenerative Cells (ADRC)
Adipose Derived Regenerative Cells (ADRC) will be harvested through autologous liposuction and processed outside the body autologous transplantation..




Primary Outcome Measures :
  1. Safety, as measured by the type of serious adverse events related to Hip Decompression supplemented with autologous ADRC transplantation compared to Hip Decompression alone. [ Time Frame: End of the study (24 months) ]
    Serious adverse events will only include those that are determined to be related to the transplantation of ADRC and/or Hip Decompression

  2. Safety, as measured by the number of serious adverse events related to Hip Decompression supplemented with autologous ADRC transplantation compared to Hip Decompression alone. [ Time Frame: End of the study (24 months) ]
    Serious adverse events will only include those that are determined to be related to the transplantation of ADRC and/or Hip Decompression


Secondary Outcome Measures :
  1. Efficacy, as measured by change in MRI lesion volume. [ Time Frame: PreoperativeVisit, Month 12 ]
    Preoperative MRI and 1 year postoperative MRI will be compared based on formal quantification of the osteonecrotic lesion volume size.

  2. Efficacy, as change measured by patient reported outcome metrics via the Hip Dysfunction and Osteoarthritis Outcome Score (HOOS) [ Time Frame: Baseline, Month 24 ]

    The HOOS is a 40 item self-report questionnaire with 5 subsets. The five subscales include 10 items on pain, 5 items for symptoms (3 symptoms items, 2 stiffness items) 17 items for activities for daily living (ADLs), 4 items for sports and recreations, and 4 items for hip related quality of life.

    Scoring: Each question contains five answer choices ranging from never (score of 0) to extreme (score of 4). A normalized score is calculated for each subscale with 0 indicating extreme symptoms and 100 representing no symptoms.


  3. Efficacy, as change measured by patient reported outcome metrics via the 12 Question Short Form (SF-12) [ Time Frame: Baseline, Month 24 ]
    The SF-12 uses 12 questions to measure functional health and well-being from a patient's point of view. It measures eight concepts commonly represented in widely used surveys: physical functioning, role limitation due to physical health problems, bodily pain, general health, vitality (energy/fatigue), social functioning, role limitations due to emotional problems and mental health distress and psychological well-being). We will use the standard 4 week recall version.

  4. Efficacy, as change measured by patient reported outcome metrics via University of California Los Angeles (UCLA) Activity Score [ Time Frame: Baseline, Month 24 ]
    The UCLA Activity Score is a simple scale ranging from 1 to 10. The patient indicates their most appropriate activity level, with 1 defined as "no physical activity, dependent on others" and 10 defined as "regular participation in impact sports".

  5. Efficacy, as change measured by patient reported outcome metrics via Harris Hip Score (HHS) [ Time Frame: Baseline, Month 24 ]
    The Harris Hip Score (HHS) has 10 question items and scores range from 0-100 with higher scores representing less dysfunction and better outcomes

  6. Sterility of ADRC samples as measured by gram stain and culture. [ Time Frame: Day of surgery ]
    Following cell processing in the Celution System, sterility testing will be performed using gram stain. A negative gram stain test result is required for ADRC samples prior to injection. If the gram stain is positive the regenerative product administration procedure must be stopped.

  7. Cell counts of the ADRC transplanted in the subject. [ Time Frame: Through study completion, approximately month 24 ]
    Cell products will be tested at the point-of-care for sterility. The remainder of the quality control sample will be returned to the laboratory for analysis of cell counts and functionality to work towards product standardization and monitoring.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Males and females 18-70 years of age.
  • Diagnosis of Steinberg Classification osteonecrosis (Stages < IIC) as measured by MRI.
  • Target disease or condition: Bilateral pre-collapse osteonecrosis of the femoral head.
  • Atraumatic osteonecrosis of the femoral head (all other etiologies eligible including corticosteroid and alcohol induced osteonecrosis).
  • Ability to safely undergo liposuction that will result in the harvest of a sufficient quantity of adipose tissue (approximately 300 mL)
  • Capacity to provide informed consent
  • Ability to comply with protocol
  • Normal laboratory values of complete blood count (CBC), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), Bilirubin, blood urea nitrogen (BUN) and Creatinine. If any value is abnormal, then the patient must be under active monitoring by appropriate subspecialist.

Exclusion Criteria:

  • Post traumatic femoral head osteonecrosis.
  • Osteonecrosis of the femoral head (stages ≥ IIIA) according to the Steinberg classification.
  • Asymptomatic osteonecrosis on exam
  • Flattening of the femoral head (Steinberg classification Type IV) or articular cartilage collapse at the time of core decompression surgery.
  • Septic arthritis, stress fracture, or non-osteonecrosis metabolic bone diseases (e.g., Paget's disease of bone, osteogenesis imperfecta, primary hyperparathyroidism, osteopetrosis, and fibrous dysplasia including monostotic, polyostotic, and McCune-Albright syndrome.
  • Skeletal immaturity.
  • Known history of HIV, or has active Hepatitis B or active Hepatitis C.
  • Disease or medication-related disorder of coagulation (i.e., elevated partial thromboplastin time (PTT) >13.8 seconds, international normalized ratio (INR) >1.2, or low platelet count <150x109/L). Patients on coumadin, heparin products, and novel oral anticoagulants will be excluded. Antiplatelet medications (e.g. aspirin, clopidogrel) are permitted as long as the aforementioned coagulation labs are within the specified range.
  • Fibromyalgia, lumbar radiculopathy, and/or neurogenic or vascular claudication.
  • Skin infection or any abnormal skin pathology at the time of surgery.
  • Local bone infection at the time of surgery.
  • Patients in active treatment for cancer or a blood dyscrasia, or having received chemotherapy, radiotherapy or immunotherapy in past 1 year.
  • Participation in another clinical study in the past 30 days or concurrent participation in another clinical trial.
  • MRI-incompatible internal devices (pacemakers, aneurysm clips, etc).
  • Patients with poorly controlled diabetes mellitus (HbA1C ≥ 8%), peripheral neuropathy, or known concomitant vascular problems.
  • Patients receiving treatment with hematopoietic growth factors or anti-vasculogenesis or anti-angiogenesis treatment (e.g., anti-VEGF).
  • Patients requiring bisphosphonate treatment after the procedure.
  • Pregnant or lactating female patients.
  • Prisoners.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269409


Contacts
Contact: Pam J Draayer 507-284-1175 draayer.pamela@mayo.edu
Contact: Teron T Cox 507-538-3560 cox.teron@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Rafael J Sierra Mayo Clinic

Responsible Party: Rafael J. Sierra, M.D., Professor of Orthopedics, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03269409     History of Changes
Other Study ID Numbers: 16-003846
First Posted: August 31, 2017    Key Record Dates
Last Update Posted: July 11, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Osteonecrosis
Bone Diseases
Musculoskeletal Diseases
Necrosis
Pathologic Processes
Coal Tar
Keratolytic Agents
Dermatologic Agents