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Use of Bone Marrow Concentrate for Treatment of Alar, Accessory, and Transverse Ligament Injuries

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03517761
Recruitment Status : Recruiting
First Posted : May 7, 2018
Last Update Posted : August 5, 2020
Sponsor:
Information provided by (Responsible Party):
Regenexx, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Craniocervical Injuries Biological: Bone Marrow Concentrate treatment Other: Sham Control Not Applicable

Detailed Description:

This study will be a single-center, prospective, single-blinded, randomized, controlled study of patients with CCJ instability that are randomized to either 2 bone marrow concentrate (BMC) treatments or 2 sham procedure to evaluate the safety and effectiveness of using an anterior approach through the posterior oropharynx for treating alar and transverse ligament injuries in addition to upper cervical injection treatment. Patients will undergo a bone marrow aspiration of approximately 30-60 cc from the posterior superior iliac crest for each procedure. 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 for those in the treatment group. While under unconscious TIVA anesthesia, the injectate is then injected under fluoroscopy into the area in need of treatment using an anterior approach through the posterior oropharynx with direct visualization of the injection site via endoscopy. Patients will be repositioned in the prone position to then receive upper cervical injections to C0-C3 ligaments and facets. Patients assigned to the sham control condition 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 those pokes to mimic the upper cervical injections to the C0-C3 ligaments and facets. In this group, the BMC will be donated for research purposes and not used clinically. Study patients will be evaluated at 3 months after the 2nd procedure months using patient reported clinical outcome questionnaires and digital motion x-ray. Control patients can crossover to the treatment group after being unblinded at 3-months after the 2nd procedure.

As an alternative to invasive surgery, ligament injections of proliferant agents (prolotherapy) have been proposed to treat cervical instability. Our group has used a blinded flexion-extension radiography to demonstrate that injections of cervical proliferant agents (hypertonic dextrose) into the supraspinous and interspinous ligaments can objectively reduce excessive cervical translation in flexion (Centeno et al. 2005). More recently we have published on the use of bone marrow concentrate to demonstrate MRI evidence of robust ACL ligament signal changes consistent with healing and repair (Centeno et al. 2015).

One of the challenges of treating the upper cervical ligaments through injection is that they can't be accessed from the posterior due to obstruction from the cervical spinal cord.Our group has developed an injection technique using an anterior approach through the posterior oropharynx, which allows direct access to the ligaments for injection. The goal of this study is to evaluate the effectiveness of this procedure in carefully selected CCJ instability patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Single-center, prospective, single-blinded, randomized, controlled study to include 80 subjects total, 40 treated with Bone Marrow Concentrate and 40 subjects treated with a Sham Procedure with cross-over from the sham to active group at 6 months
Masking: Single (Participant)
Masking Description: Participants are blind to treatment condition until 6 months post-procedure. Participants in sham control group can crossover to treatment group at that time.
Primary Purpose: Treatment
Official Title: A Single-Blinded, Randomized Controlled Trial Evaluating the Use of Bone Marrow Concentrate for the Treatment of Alar, Accessory, and Transverse Ligament Injuries
Actual Study Start Date : March 23, 2018
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : June 2025

Arm Intervention/treatment
Experimental: Bone Marrow Concentrate treatment
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.
Biological: Bone Marrow Concentrate treatment
While under unconscious TIVA anesthesia, the injectate is then injected under fluoroscopy into the area in need of treatment using an anterior approach through the posterior oropharynx with direct visualization of the injection site via endoscopy. The alar, transverse, and accessory ligaments are the target areas to be treated with the bone marrow concentrate injectate. Patients will be repositioned in the prone position to then receive upper cervical injections to C0-C3 ligaments and facets.Patients will receive 2 of these treatment procedures 3 months apart.

Sham Comparator: Sham Control
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.
Other: Sham Control
Control subjects will receive a sham procedure of a small skin puncture to the posterior oropharynx guided under fluoroscopy while under anesthesia.Patients will also receive small skin punctures to the back of the neck to mimic ligament and facet injections. Patients will receive 2 of these procedure 3 months apart.




Primary Outcome Measures :
  1. Headache Impact Test score change from baseline [ Time Frame: Change from Baseline to 3 months after 2nd treatment ]
    The difference between treatment groups in the within patient mean change from baseline to 6 months in Headache Impact Test scores.


Secondary Outcome Measures :
  1. Neck Disability Index score change from baseline [ Time Frame: Change from baseline to 3 months after 2nd treatment ]
    Difference between groups in changes scores for Neck Disability Index scores from baseline and 6 months.

  2. Neck Disability Index score change from baseline [ Time Frame: Change from baseline to 6 months after 2nd treatment ]
    Difference between groups in changes scores for Neck Disability Index scores from baseline and 12 months.

  3. Short Form Health Survey change from baseline [ Time Frame: Change from baseline to 3 months after 2nd treatment ]
    Difference between groups in changes scores for Short Form Health Survey scores from baseline and 6 months.

  4. Short Form Health Survey change from baseline [ Time Frame: Change from baseline to 6 months after 2nd treatment ]
    Difference between groups in changes scores for Short Form Health Survey scores from baseline and 12 months.

  5. Numeric Pain Scale change from baseline [ Time Frame: Change from baseline to 3 months after 2nd treatment ]
    Difference between groups in changes scores for numeric pain scores from baseline and 6 months, where 0=no pain and 10=worst possible pain.

  6. Numeric Pain Scale change from baseline [ Time Frame: Change from baseline to 6 months after 2nd treatment ]
    Difference between groups in changes scores for numeric pain scores from baseline and 12 months, where 0=no pain and 10=worst possible pain.

  7. Single Assessment Numeric Evaluation improvement rating -modified [ Time Frame: mean at 3 months after 2nd treatment ]
    Difference between groups for mean improvement scores at 6 months, where -100=100% worse from baseline and 100=100% better or improved from baseline

  8. Single Assessment Numeric Evaluation improvement rating -modified [ Time Frame: mean at 6 months after 2nd treatment ]
    Difference between groups for mean improvement scores at 12 months, where -100=100% worse from baseline and 100=100% better or improved from baseline

  9. Adverse events [ Time Frame: Thru 6 month post procedure after 2nd treatment ]
    Any complication of adverse event

  10. C1-C2 overhang [ Time Frame: 3 months after 2nd treatment ]
    Post-op DMX studies will also be used to quantify any reduction in C1-C2 overhang or ADI.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-1) Voluntary signature of the IRB approved Informed Consent, 2) Skeletally mature Male or Female ages 18 to 65 3) Must have a specific inciting injury event that occurred less than 10 years ago where the patient experienced trauma that caused the problem-meaning from that day on, they had the symptoms for which they are now seeking treatment 4) Upper cervical symptoms predominate: Patient must have a headache since the event and must have one of the following: dizziness, vertigo, imbalance, or visual disturbances 5) Patient must be able to care for themselves without assistance 6) NDI percentage score (raw NDI score times 2) at least 30 (moderate disability) 7) Imaging: Must have DMX lateral overhang of C1 on C2 in lateral bending open mouth view of at least 3mm or grabb-oakes of >9mm on cervical flexion MRI-change in signal on static imaging does not qualify the patient 8) Has not responded long-term to conservative care 9) Upper cervical fusion candidate 10) Exam is c/w upper cervical injury (i.e. tenderness along upper cervical facet joints and/or musculature/skull base, proprioceptive difficulties)

11) Is independent, ambulatory, and can comply with all post-operative evaluations and visits 12) Patient states strong desire to avoid surgery

Exclusion criteria:

13) Known or diagnosed EDS based on Beighton criteria: https://www.physio-pedia.com/Beighton_score 14) Lower or mid-cervical symptomatic disease (tenderness in mid to lower cervical facets, radiculopathy, radiating symptoms into shoulder blade, epicondylitis, numbness and tingling in hands) 15) Prior spinal fusion or surgery at any segment in cervical, thoracic, or lumbar spine 16) NDI % score > than 56 (severe disability), unless at the discretion of the independent physician review 17) Prior or current history of a metabolic disorder like diabetes, anorexia, other eating disorder, BMI>40 18) 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) 19) Prior epidural or other milligram dose steroid injection in any area within the past 6 months 20) Prior prolotherapy or platelet-based injections to the cervical spine within the last 3 months 21) Prior radiofrequency ablation to the cervical spine within the last 2 years 22) Physical infirmity that is incompatible with the procedure and/or anesthesia required for same 23) Unable to tolerate the injection position 24) Abnormal anatomy seen on MRI imaging that would make the procedure higher risk (e.g. congenital atlanto-axial fusion, atlas assimilation, upper cervical fracture or surgical fusion) 25) Inflammatory or auto-immune based pathology (e.g., rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, polymyalgia, polymyositis, gout, pseudo gout) 26) Quinolone or Statin induced myopathy/tendinopathy 27) Condition represents a worker's compensation case 28) Currently involved in a health-related litigation procedure 29) Is pregnant 30) Bleeding disorders 31) Currently taking anticoagulant or immunosuppressive medication 32) Allergy or intolerance to study medication 33) Use of and significant physical dependence on a chronic opioid (>20 mg oxycodone equivalent per day) 34) Documented history of drug abuse within six months of treatment 35) Any other condition, that in the opinion of the investigator, that would preclude the patient from enrollment


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): NCT03517761


Contacts
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Contact: Ehren R Dodson, PhD 720-287-7199 edodson@regenexx.com
Contact: Neven Steinmetz, PhD nsteinmetz@regenexx.com

Locations
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United States, Colorado
Ehren Dodson Recruiting
Broomfield, Colorado, United States, 80021
Contact: Ehren Dodson, PhD    720-287-7199    edodson@regenexx.com   
Contact: Neven Steinmetz, PhD    3034296448 ext 141    nsteinmetz@regenexx.com   
Principal Investigator: Christopher Centeno, MD         
Sub-Investigator: John Schultz, MD         
Sub-Investigator: John Pitts, MD         
Sub-Investigator: Jason Markle, DO         
Sponsors and Collaborators
Regenexx, LLC
Investigators
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Principal Investigator: Christopher Centeno, MD Regenexx, LLC
Publications:
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Responsible Party: Regenexx, LLC
ClinicalTrials.gov Identifier: NCT03517761    
Other Study ID Numbers: RSI2017-RCT01
First Posted: May 7, 2018    Key Record Dates
Last Update Posted: August 5, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regenexx, LLC:
CCJ
Bone Marrow Concentrate
Stem Cell Therapy
Alar Ligament
Transverse Ligament
Additional relevant MeSH terms:
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Trauma, Nervous System
Wounds and Injuries
Nervous System Diseases