OsteonecrosisPhase 1NCT03269409
Use of Adipose Derived Regenerative Cells in Bilateral Femoral Head Osteonecrosis
A Phase 1 study testing Lactated Ringers, The Celution 800/GP System (Cytori Therapeutics) and Adipose Derived Regenerative Cells (ADRC) in people with Osteonecrosis, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 70 years
- Conditions the study is for
- Osteonecrosis
- What is being tested?
- Lactated Ringers, The Celution 800/GP System (Cytori Therapeutics) and Adipose Derived Regenerative Cells (ADRC)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2017to 28 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females 22-70 years of age.
- No articular surface collapse of the femoral heads 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 360 mL). A plastic surgeon evaluation will be performed in order to determine adequate adipose tissue is available for harvest.
- Capacity to provide informed consent
- Ability to comply with protocol
- Normal laboratory values of CBC, CRP, AST, ALT, Bilirubin (total \& direct), BUN and Creatinine.
Who cannot join
- Post traumatic femoral head osteonecrosis.
- Osteonecrosis of the femoral head in 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.
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- Known history of HIV, or has active Hepatitis B or active Hepatitis C.
- Disease or medication-related disorder of coagulation (i.e., elevated PTT >13.8 seconds, 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.
- Patients who have aPTT values greater than or equal to 1.8 times the normal limit.
- Patients who are actively or recently received glycoprotein IIb/IIIa inhibitors (abciximab/ ReoPro, Aggrastat/ tirofiban, eptifibatide/ Integrilin)
- All patients who have inadequate fat deposits (i.e. < 200 ml of lipoaspirate from 3 bilateral sites) will be excluded from the study.
- Lumbar radiculopathy, and/or neurogenic or vascular claudication.
- Active Skin infection at the time of surgery
- Active Local bone infection
- 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 severe vascular problems.
- Patients receiving treatment with hematopoietic growth factors or antivasculogenesis or anti-angiogenesis treatment (e.g., anti-VEGF).
- Patients requiring bisphosphonate treatment for study duration.
- Pregnant or lactating female patients.
- Prisoners.
- Known starch or gentamycin allergy
- Known amylase deficiency
- Laser- or ultrasound-assisted lipoaspiration technique is used during the lipoaspiration procedure
- An adverse event that meets one or more fat harvest stopping rules has occurred during the lipoaspiration procedure
- Positive gram stain result on ADRC product prior to administration
- If final viable cell count of ADRC product is < 34 million
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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
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 in one hip and hip decompression supplemented with adipose derived regenerative cells in patients with osteonecrosis in both of their hips.
Read the detailed description
Preclinical and clinical data suggest that ADRC may serve as a safe and efficacious adjuvant agent for the treatment of ON. However, to the authors knowledge no RCT 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 800/GP 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 CE Mark 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 800/GP 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.
- Conditions
- Osteonecrosis
- Being tested
- Lactated Ringers, The Celution 800/GP System (Cytori Therapeutics), Adipose Derived Regenerative Cells (ADRC)
- Medical subject headings
- Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactated RingersOther
Approximately 5 mls of lactated ringers will be injected after decompression into the hip that does not receive adipose derived regenerative cells.
The Celution 800/GP System (Cytori Therapeutics)Device
The Celution 800/GP 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.
Adipose Derived Regenerative Cells (ADRC)Biological
Subjects in this arm will have Adipose Derived Regenerative Cells (ADRC)harvested through autologous liposuction and processed outside the body using The Celution 800/GP System (Cytori Therapeutics) before having approximately 5 mls. of ADRCs transplanted into the femoral head after standard of care hip decompression.
| Study group | Role | What they receive |
|---|---|---|
| Hip Decompression with lactated ringers | Sham comparator | Subjects will receive standard of care hip decompression along with an injection of approximately 5 mls. of lactated ringers. Receives: Other: Lactated Ringers |
| Hip Decompression with ADRC | Experimental | Subjects in this arm will have Adipose Derived Regenerative Cells (ADRC)harvested through autologous liposuction and processed outside the body using The Celution 800/GP System (Cytori Therapeutics) before having approximately 5 mls. of ADRCs transplanted into the femoral head after standard of care hip decompression. Receives: Device: The Celution 800/GP System (Cytori Therapeutics); Biological: Adipose Derived Regenerative Cells (ADRC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, as measured by the type and number of serious adverse events related to Hip Decompression supplemented with autologous ADRC transplantation compared to Hip Decompression alone.
Serious adverse events will only include those that are determined to be related to the transplantation of ADRC and/or Hip Decompression.
Measured: End of the study (24 months)
Secondary outcomes (2)
In vitro laboratory metrics as measured by flow analysis as well as proliferation and differentiation potential of adipose and bone marrow derived mesenchymal stem cells (MSCs).
These immunophenotypic characterizations will be correlated with MRI imaging data and patient reported outcomes.
Measured: Preoperative, Month 12, and Month 24
Initial signals of efficacy as measured by MRI lesion volume quantification and patient reported outcome metrics.
Preoperative MRI, 1 and 2 year postoperative MRI osteonecrotic lesion volume size compared to quality of life and hip function scores.
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.
Measured: Preoperative, Month 12, and Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2017
- Study start15 Nov 2017
- Primary completion28 Jun 2021
- Study completion28 Jun 2021
Why it stopped: Logistical delays from device manufacturer due to COVID
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteonecrosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Cytori Celution 800/GP System to process ADRC from lipoaspirate at the point of care.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rafael J. Sierra, M.D., Mayo Clinic
- Investigators
- Rafael J Sierra, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03269409
- Sponsor's protocol ID
- 16-003846
- Status last verified
- Dec 2021
- First submitted
- 29 Aug 2017
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03269409
- Acronym / sponsor ID
- 16-003846
- Conditions
- Osteonecrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Logistical delays from device manufacturer due to COVID
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 28 Jun 2021 (actual)
- Study completion
- 28 Jun 2021 (actual)
- First posted
- 31 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 in one hip and hip decompression supplemented with adipose derived regenerative cells in patients with osteonecrosis in both of their hips.
Detailed description
Preclinical and clinical data suggest that ADRC may serve as a safe and efficacious adjuvant agent for the treatment of ON. However, to the authors knowledge no RCT 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 800/GP 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 CE Mark 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 800/GP 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Cytori Celution 800/GP System to process ADRC from lipoaspirate at the point of care.
| Arm | Type | Receives |
|---|---|---|
| Hip Decompression with lactated ringers | Sham comparator | Other: Lactated RingersSubjects will receive standard of care hip decompression along with an injection of approximately 5 mls. of lactated ringers. |
| Hip Decompression with ADRC | Experimental | Device: The Celution 800/GP System (Cytori Therapeutics), Biological: Adipose Derived Regenerative Cells (ADRC)Subjects in this arm will have Adipose Derived Regenerative Cells (ADRC)harvested through autologous liposuction and processed outside the body using The Celution 800/GP System (Cytori Therapeutics) before having approximately 5 mls. of ADRCs transplanted into the femoral head after standard of care hip decompression. |
Who may qualify
- Ages
- 22 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males and females 22-70 years of age.
- No articular surface collapse of the femoral heads 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 360 mL). A plastic surgeon evaluation will be performed in order to determine adequate adipose tissue is available for harvest.
Key exclusion criteria (28 listed)
- Post traumatic femoral head osteonecrosis.
- Osteonecrosis of the femoral head in 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactated RingersApproximately 5 mls of lactated ringers will be injected after decompression into the hip that does not receive adipose derived regenerative cells. | Other | Hip Decompression with lactated ringers |
| The Celution 800/GP System (Cytori Therapeutics)The Celution 800/GP 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. | Device | Hip Decompression with ADRC |
| Adipose Derived Regenerative Cells (ADRC)Subjects in this arm will have Adipose Derived Regenerative Cells (ADRC)harvested through autologous liposuction and processed outside the body using The Celution 800/GP System (Cytori Therapeutics) before having approximately 5 mls. of ADRCs transplanted into the femoral head after standard of care hip decompression. | Biological | Hip Decompression with ADRC |
Primary outcome
Safety, as measured by the type and 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.
2 secondary outcomes
In vitro laboratory metrics as measured by flow analysis as well as proliferation and differentiation potential of adipose and bone marrow derived mesenchymal stem cells (MSCs).
Time frame: Preoperative, Month 12, and Month 24
Initial signals of efficacy as measured by MRI lesion volume quantification and patient reported outcome metrics.
Time frame: Preoperative, Month 12, and Month 24
Results and safety
The study was stopped early (reason given: Logistical delays from device manufacturer due to COVID). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rafael J Sierra, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lactated Ringers, The Celution 800/GP System (Cytori Therapeutics) and Adipose Derived Regenerative Cells (ADRC) in people with Osteonecrosis, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Logistical delays from device manufacturer due to COVID). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, as measured by the type and 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.