Bone Marrow Concentrate for Craniocervical Injury

Overseen By Neven Steinmetz, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Regenexx, LLC

Must not be taking: Anticoagulants, Immunosuppressives, Opioids, others

Disqualifiers: EDS, Diabetes, Auto-immune, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 months

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the effectiveness of using anterior approach through the posterior oropharynx for treating alar and transverse ligament injuries with bone marrow concentrate for patients with craniocervical junction (CCJ) instability.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking anticoagulant (blood-thinning) or immunosuppressive medications.

What data supports the effectiveness of the treatment Bone Marrow Concentrate for Craniocervical Injury?

Research shows that Bone Marrow Aspirate Concentrate (BMAC) is used for treating various orthopedic conditions, including osteoarthritis and knee injuries, suggesting potential benefits for similar injuries. However, the effectiveness can vary due to different preparation methods and the variability in stem cells and growth factors. ^{1 2 3 4 5}

Is Bone Marrow Concentrate treatment safe for humans?

The safety of Bone Marrow Concentrate (BMC) treatment in humans is still being studied, and while it is used for various conditions like osteoarthritis, its safety compared to other treatments is not yet fully determined. ^{1 2 4 5 6}

How is Bone Marrow Concentrate treatment different from other treatments for craniocervical injury?

Bone Marrow Concentrate treatment is unique because it uses a patient's own bone marrow cells, which are concentrated and injected to potentially aid in healing, unlike traditional treatments that may not involve cell-based therapy. This approach is still being studied for its effectiveness and safety compared to other treatments. ^{4 5 6 7 8}

Research Team

Christopher Centeno, MD

Principal Investigator

Regenexx, LLC

Eligibility Criteria

This trial is for men and women aged 18-65 who have had a traumatic injury to the head or neck within the last 10 years, leading to instability at where the skull meets the spine. They should be able to care for themselves, have moderate disability from their condition, and not responded well to other treatments. Candidates are those wanting to avoid surgery but show signs of upper cervical injury.

Inclusion Criteria

Exam is c/w upper cervical injury (i.e. tenderness along upper cervical facet joints and/or musculature/skull base, proprioceptive difficulties)

My condition hasn't improved with standard treatments.

Must have a specific inciting injury event that occurred less than 10 years ago where the patient experienced trauma that caused the problem

Exclusion Criteria

Unable to tolerate the injection position

Known or diagnosed EDS based on Beighton criteria

Unable to tolerate injections due to central sensitization (i.e. significant intolerance to manual therapy such as massage, activity such as physical therapy, or an exaggerated pain response to prior injection therapy)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 bone marrow concentrate treatments or 2 sham procedures to evaluate the safety and effectiveness of the treatment

3 months

2 procedures

Follow-up

Participants are monitored for safety and effectiveness after treatment using patient-reported clinical outcome questionnaires and digital motion x-ray

3 months

1 visit (in-person)

Long-term Follow-up

Participants are monitored for changes in pain scores and other health metrics up to 12 months

6-12 months

Treatment Details

Interventions

• Bone Marrow Concentrate treatment
• Sham Control

Trial Overview The study tests bone marrow concentrate treatment's effectiveness against a sham control in treating ligament injuries at the craniocervical junction (where the skull meets the spine). The treatment involves an anterior approach through the back of the mouth area.

Participant Groups

Group I: Bone Marrow Concentrate treatment Experimental Treatment 1 Intervention

Bone marrow concentrate subjects will undergo a bone marrow aspiration of approximately 30-60 cc. Platelet rich plasma (PRP) and platelet lysate (PL) will be derived from the bone marrow aspirate and later mixed with the bone marrow nucleated cell layer. Injectate will then be used to treat the ligaments in the CCJ and upper cervical injections to C0-C3 ligaments and facets.

Group II: Sham Control Placebo Group 1 Intervention

Control subjects will also undergo a bone marrow aspiration of 30-60 cc to maintain blinding. Control subjects will receive a sham procedure of a small skin puncture to the posterior oropharynx guided under fluoroscopy while under anesthesia as well as receive sham upper cervical injections to C0-C3 ligaments and facets.

Bone Marrow Concentrate treatment is already approved in United States, European Union for the following indications:

Approved in United States as Bone Marrow Aspirate Concentrate for:

• Orthopedic injuries
• Musculoskeletal conditions
• Osteoarthritis
• Tendon and ligament injuries
• Cartilage injuries
• Fractures
• Osteonecrosis

Approved in European Union as Bone Marrow Aspirate Concentrate for:

• Orthopedic injuries
• Musculoskeletal conditions
• Osteoarthritis
• Tendon and ligament injuries
• Cartilage injuries
• Fractures
• Osteonecrosis

Who Is Running the Clinical Trial?

Regenexx, LLC

Lead Sponsor

Trials

15

Recruited

50,800+

Findings from Research

Bone marrow aspirate concentrate (BMAC) injections show promise for treating osteoarthritis (OA), with 22 studies involving 4626 patients indicating overall safety and low adverse events.

Most studies reported improvements in pain and function, but significant variability in study quality and methodology suggests that more rigorous, large-scale trials are needed to confirm BMAC's effectiveness in OA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application. Cavallo, C., Boffa, A., Andriolo, L., et al.[2022]

Bone marrow aspirate concentrate (BMAC) shows potential for treating knee cartilage defects, with clinical studies indicating improved outcomes compared to traditional methods like microfracture, although the overall quality of these studies is low.

Animal studies have produced inconsistent results regarding the efficacy of BMAC, and the cells in BMAC do not meet the criteria for mesenchymal stem cells, suggesting that further research is needed to fully understand its mechanism and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Bone Marrow Aspirate Concentrate for the Treatment of Focal Chondral Lesions of the Knee: A Systematic Review and Critical Analysis of Animal and Clinical Studies. Cavinatto, L., Hinckel, BB., Tomlinson, RE., et al.[2020]

In a study involving 10 patients with maxillary bone deficiency, the use of bone marrow aspirate concentrate (BMAC) with bone allograft led to significantly higher bone density in the buccal region compared to the control group without BMAC.

Although bone volume loss was significant in the group receiving BMAC, the overall pattern of bone formation was improved, indicating that BMAC may enhance the quality of bone regeneration in maxillary reconstructions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Bone Allograft With or Without Bone Marrow Aspirate Concentrate in Appositional Reconstructions: A Tomographic and Histomorphometric Study. Lavareda Corrêa, SC., Elias de Sousa, J., Pasquali, PJ., et al.[2022]

Bone marrow aspirate (BMA) contains a higher concentration of mesenchymal stem cells (MSCs) and more colony-forming units (CFUs) compared to bone marrow aspirate concentrate (BMAC), indicating that BMA may be more effective for cell-based therapies.

BMAC failed to concentrate MSCs in 6 out of 8 samples tested, highlighting significant variability in MSC quantity and potency between BMA and BMAC, which raises concerns about the reliability of BMAC for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique. Brozovich, A., Sinicrope, BJ., Bauza, G., et al.[2022]

The Harvest SmartPrep 3 system demonstrated greater consistency in concentrating white blood cells compared to the Arthrex Angel system, indicating it may be more reliable for certain therapeutic applications.

Different BMAC preparation systems yield varying compositions of cell types, with Harvest recovering the highest percentages of colony-forming unit-fibroblasts and CD34+ cells, while Biomet excelled in platelet recovery, suggesting that each system has unique advantages for specific treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Consistency and Composition of Commercially Available Bone Marrow Aspirate Concentrate Systems. Dragoo, JL., Guzman, RA.[2022]

Intra-articular injections of bone marrow aspirate concentrate (BMC) for early knee and hip osteoarthritis showed significant improvement in patient-reported outcomes, with scores decreasing from 40.8% to 20.6% (P < .001) over an average follow-up of 13.2 months.

The treatment was deemed safe, with a satisfaction rate of 63.2%, and 64% of patients achieved the minimal clinically important difference, although two patients required total hip arthroplasty within 8 months post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Clinical Outcomes of Intra-Articular Injections of Bone Marrow Aspirate Concentrate for the Treatment of Early Osteoarthritis of the Hip and Knee: A Cohort Study. Rodriguez-Fontan, F., Piuzzi, NS., Kraeutler, MJ., et al.[2022]

In a study of 29 patients with symptomatic ACL tears, 77% showed significant improvement in ACL integrity after receiving autologous bone marrow concentrate (BMC) injections, indicating its potential as an effective non-surgical treatment option.

Patients reported an average improvement of 72% in their symptoms at around 23 months post-treatment, with significant reductions in pain and improved functional scores measured at multiple time points, suggesting long-term benefits of BMC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow concentrate and platelet products: a non-controlled registry study. Centeno, C., Markle, J., Dodson, E., et al.[2019]

Bone marrow aspirate concentrate (BMAC) is safe for treating knee pain due to osteoarthritis, with no serious adverse events reported in a study of 25 patients.

Both BMAC and saline injections resulted in significant pain relief over time, but there was no significant difference in pain reduction between the two treatments, suggesting that further research is needed to understand the true efficacy of BMAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Shapiro, SA., Kazmerchak, SE., Heckman, MG., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The Role of Bone Marrow Aspirate Concentrate for the Treatment of Focal Chondral Lesions of the Knee: A Systematic Review and Critical Analysis of Animal and Clinical Studies. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Use of Bone Allograft With or Without Bone Marrow Aspirate Concentrate in Appositional Reconstructions: A Tomographic and Histomorphometric Study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the Consistency and Composition of Commercially Available Bone Marrow Aspirate Concentrate Systems. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Early Clinical Outcomes of Intra-Articular Injections of Bone Marrow Aspirate Concentrate for the Treatment of Early Osteoarthritis of the Hip and Knee: A Cohort Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Symptomatic anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow concentrate and platelet products: a non-controlled registry study. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. [2022]