Cellular & Biocellular Regenerative Therapy in Musculoskeletal Pain, Dysfunction,Degenerative or Inflammatory Disease (BRT)

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ClinicalTrials.gov Identifier: NCT03090672

Recruitment Status : Recruiting

First Posted : March 27, 2017

Last Update Posted : January 18, 2020

See Contacts and Locations

Sponsor:

Collaborators:

Regeneris Medical

Global Alliance for Regenerative Medicine

Information provided by (Responsible Party):

Robert W Alexander, MD, Regeneris Medical

Study Description

Brief Summary:

Musculoskeletal disorders and degeneration represent injuries or pain in the body's joint ligaments, tendons, muscles, nerves, and skeletal elements that support extremities, spine and related tissues. Direct injuries and aging contribute to breakdown and inflammation of these tissues, leading to debilitation and loss of function in these areas. This has major impact on quality of life, occupational/recreation limitations, and psychosocial implications.

Many therapies have been employed including medications, physical therapy, occupational therapy, and a variety of surgical interventions each of which have distinct limitations, often covering the issues versus providing actual healing and return to function. Many reports are now available utilizing self-healing options which include use of stem/stromal cellular therapy or biocellular treatments (either from adipose or marrow) using targeted placement of cells, matrix and platelet concentrates. Termed cellular or Biocellular therapy (typically optimized using ultrasound guidance). It is proposed that use of cellular isolates or cell-stroma derived from the largest deposit of these cells (adipose greater than marrow), may use in conjunction with targeted placement or as a stand alone methodology intravascular use.

This study is designed as a interventional means to examine the safety and efficacy of the use of cellular and tissue stromal vascular fraction in musculoskeletal pain, dysfunction degeneration or inflammatory disorders.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis Rheumatoid Nodule Degenerative Joint Disease Tendinopathy Tendinosis Back Pain	Drug: Normal Saline Procedure: Tissue Stromal Vascular Fraction Biological: Platelet Rich Plasma Procedure: Cellular Stromal Vascular Fraction	Not Applicable

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Detailed Description:

Many therapies have been employed including medications, physical therapy, occupational therapy, and a variety of surgical interventions each of which have distinct limitations, often covering the issues versus providing actual healing and return to function. Many reports are now available utilizing self-healing options which include use of stem/stromal cells (either from adipose or marrow) using targeted placement of cells, matrix and platelet concentrates. This is termed Biocellular therapy, and typically is optimized by use of ultrasound guidance. It is proposed that use of cellular isolates derived from the largest deposit of these cells (adipose greater than marrow), may use in conjunction with targeted placement or as a stand alone methodology of parenteral use.

This study is designed as a interventional means to examine the safety and efficacy of the use of cellular stromal vascular fraction (cSVF) in musculoskeletal pain, dysfunction degeneration or inflammatory disorders. The important cellular components represent, not the adipocyte, but the heterogeneous cell group associated with the peri-vasculature. The group does include certain cells referred to as "stem" or "stromal" cells, and are considered key elements of cellular and biocellular treatments. The carrier microvascular tissue, adipose, has been shown to not participate in wound healing or cellular replacement per se. It is well established that those perivascular (adventitial) cell types are found in essentially all tissues of the body, but in highest numbers in the easily accessed depots with the subdermal fat. It is proposed that areas of these groups are responded to as a result of "signaling" to permit a chemotactic request for needed growth factors and cytokines which effectively contribute to the healing capability at failing or damaged sites. This Trial will investigate the safety/efficacy of either combining specific targeting (ultrasound) with and/or without systemic parenteral route introduction.

This study includes closed syringe, disposable microcannula harvesting of subdermal fat tissues for obtaining the native perivascular stromal elements (extracellular matrix (ECM) and periadventitial cells shown to be multipotent (in potentials), incubation, digestion and isolation of cSVF. This isolated and concentration of stem/stromal cellular pellet (without actual extracellular matrix or stromal scaffolding elements) is then suspended in 500 cc sterile Normal Saline (NS) and deployed via peripheral intravenous route. Evaluations of safety issues are measured at intervals (both severe and non-severe categories) and by ultrasound and imaging studies.

Biocellular treatments are defined as use of tissue stromal vascular fraction (tSVF) obtained within adipose tissue complex (ATC), combined with high density platelet rich plasma (HD PRP) concentrated from standard blood draw. Concentration in FDA approved platelet concentrate devices to achieve levels of >4 times patient's own measured baseline levels. Such concentrates have been shown to provide important growth factors and cytokines (signal proteins) naturally involved in wound healing and repair functions. A form of Cell-Enriched Biocellular Therapy (CEBT) is available as a component of this study, in which the tSVF + HD PRP can be enhanced in cellular numbers via the process of isolating and concentrating cSVF discussed above. Many small case series and case reports have been published in the peer reviewed medical literature which suggest that these interventions are both safe and effective at relieving musculoskeletal disorders included in the study.

This study in intended to provide evidence of a non-drug safety and efficacy using both of these interventions. Evaluation and tracking of adverse events or severe adverse events (SAE) will be tracked according to intervals described. Examination of the optimal numbers of cells, viability of such cells, and evaluation of the efficacy will be statistically studied reported relative outcomes.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	300 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Use of Cellular and Biocellular Therapy in Musculoskeletal Pain, Dysfunction, Degenerative or Inflammatory Disease
Actual Study Start Date :	March 11, 2017
Estimated Primary Completion Date :	August 31, 2021
Estimated Study Completion Date :	December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Osteoarthritis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: tSVF + PRP Arm1 Stromal Vascular Fraction tSVF + Platelet Rich Plasma (PRP) concentrate	Procedure: Tissue Stromal Vascular Fraction tSVF Biological: Platelet Rich Plasma PRP
Experimental: tSVF + PRP + cSVF Enrichment Arm 2 tissue Stromal Vascular Fraction (tSVF) + Platelet-Rich Plasma (PRP) concentration + (cSVF)	Procedure: Tissue Stromal Vascular Fraction tSVF Biological: Platelet Rich Plasma PRP Procedure: Cellular Stromal Vascular Fraction cSVF
Experimental: Normal Saline IV + cSVF Arm 3 Cellular Stromal Vascular Fraction (cSVF); Normal Saline IV introduction	Drug: Normal Saline Normal Saline IV delivery Procedure: Cellular Stromal Vascular Fraction cSVF

Outcome Measures

Primary Outcome Measures :

Participants with complications [ Time Frame: 1 month ]
Adverse and Severe Adverse Events Reports

Secondary Outcome Measures :

Change from baseline quality of life level (QoL Questionnaire) [ Time Frame: 6 months, 12 months ]
QoL Questionnaire
Change from baseline visual analog pain score [ Time Frame: 6 months, 1 year, 2 year ]
Changes of Visual Analog Pain Score (VAS) 1-10
Change from baseline of limitation of activities (Functional analysis of range of motion) [ Time Frame: baseline, 6 months, 1 year ]
Functional analysis of range of motion compared from baseline
Change from baseline of imaging if required for study entry [ Time Frame: baseline, 1 year ]
imaging

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 90 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with documented inflammatory, autoimmune (rheumatoid arthritis (RA), degeneration of musculoskeletal system
No systemic disorders which, in the opinion of the principal investigators or provider, would disqualify from being safely able to undergo needed procedures
Able to provide informed consent
Patient having adequate donor adipose (fat) tissue
Patient mature enough to tolerate the needed procedures

Exclusion Criteria:

Systemic or psychological impairment which would preclude patient tolerance and understanding of procedures and follow up
Patients with known active cancer and chemotherapy or radiation therapy
Patients with ongoing active infections
High dose steroid users or use of injections of corticoid steroids within a six month timeframe
Opiate addition or in treatment program for withdrawal
History of severe traumatic brain injuries
If, in the opinion of providers, the patient will not be able to fully cooperate or complete the study and its follow up

Contacts and Locations

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): NCT03090672

Contacts

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Contact: Ryan JP Welter, MD, PhD	508.345.5492	r.welter@regenerismedical.com
Contact: Gabrielle Lewis	508.316.4268	g.lewis@regenerismedical.com

Locations

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United States, Massachusetts
Regeneris Medical	Recruiting
North Attleboro, Massachusetts, United States, 02760
Contact: Gabrielle Lewis 508-316-4268 g.lewis@regenerismedical.com
Contact: Gabielle lEWIS 508/316.4268 g.lewis@regenerismedical.com
Regeneris Medical	Recruiting
North Attleboro, Massachusetts, United States, 02760
Contact: Ryan JP Welter, MD 508-345-5492 r.welter@regenerismedical.com
Contact: Gabrielle Lewis 508.316.4268 g.lewis@regenerismedical.com
Principal Investigator: Glenn C Terry, MD
Principal Investigator: Robert W Alexander, MD
Principal Investigator: Ryan JP Welter, MD,PhD

Sponsors and Collaborators

Robert W Alexander, MD

Regeneris Medical

Global Alliance for Regenerative Medicine

Investigators

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Principal Investigator:	Robert W Alexander, MD	GARM USA
Principal Investigator:	Glenn C Terry, MD	Global Alliance for Regenerative Medicine (GARM)
Principal Investigator:	Ryan JP Welter, MD, PhD	Regeneris Medical

More Information

Publications of Results:

Oliver, K., Alexander, RW. Combination of Autologous Adipose-Derived Tissue Stromal Vascular Fraction Plus High Density Platelet-Rich Plasma or Bone Marrow Concentrates in Achilles Tendon Tears. J. Prolo; 2013; 5: e895-912.

Other Publications:

Kuorinka I, Jonsson B, Kilbom A, Vinterberg H, Biering-Sørensen F, Andersson G, Jørgensen K. Standardised Nordic questionnaires for the analysis of musculoskeletal symptoms. Appl Ergon. 1987 Sep;18(3):233-7.

Gallagher S, Heberger JR. Examining the interaction of force and repetition on musculoskeletal disorder risk: a systematic literature review. Hum Factors. 2013 Feb;55(1):108-24. Review.

Alexander, Robert W., Understanding Mechanical Emulsification (NanoFat) Versus Enzymatic Isolation fo Tissue Stromal Vascular Fraction (tSVF) From Adipose Tissue: Potential Uses in Biocellular Regenerative Medicine. J of Prolo. 2016; 8: 3947-960.

Alexander RW. Biocellular Regenerative Medicine: Use of Adipose-Derived Stem/Stromal Cells and It's Native Bioactive Matrix. Phys Med Rehabil Clin N Am. 2016 Nov;27(4):871-891. doi: 10.1016/j.pmr.2016.06.005. Review.

Alderman, D, Alexander, R.W.,: Advances In Regenerative Medicine: High Density Platelet-Rich Plasma and Stem Cell Prolotherapy. J Pract Pain Management, 2011; Vol Oct: 49-90

Alexander, Robert W., Understanding Adipose-Derived Stromal Vascular Fraction (SVF) Cell Biology On The Basis of Perivascular Cell Components In Aesthetic and Regenerative Medicine. J. Prolo; 2012; 4: e13777

Alexander RW, Harrell DB. Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting. Clin Cosmet Investig Dermatol. 2013 Apr 8;6:91-102. doi: 10.2147/CCID.S40575. Print 2013.

Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. A systematic review of recommendations and guidelines for the management of osteoarthritis: The chronic osteoarthritis management initiative of the U.S. bone and joint initiative. Semin Arthritis Rheum. 2014 Jun;43(6):701-12. doi: 10.1016/j.semarthrit.2013.11.012. Epub 2013 Dec 4. Review.

Katz JN, Brownlee SA, Jones MH. The role of arthroscopy in the management of knee osteoarthritis. Best Pract Res Clin Rheumatol. 2014 Feb;28(1):143-56. doi: 10.1016/j.berh.2014.01.008. Review.

Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. BMJ. 2015 Jun 16;350:h2747. doi: 10.1136/bmj.h2747. Review.

Burdett N, McNeil JD. Difficulties with assessing the benefit of glucosamine sulphate as a treatment for osteoarthritis. Int J Evid Based Healthc. 2012 Sep;10(3):222-6. doi: 10.1111/j.1744-1609.2012.00279.x. Review.

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Responsible Party:	Robert W Alexander, MD, Principal Investigator, Regeneris Medical
ClinicalTrials.gov Identifier:	NCT03090672
Other Study ID Numbers:	RGV MSK 1
First Posted:	March 27, 2017 Key Record Dates
Last Update Posted:	January 18, 2020
Last Verified:	January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided
Plan Description:	Comparative analysis of safety and efficacy between use of ultrasound guided tissue stromal vascular fraction (AD-tSVF) plus high density platelet rich plasma (HD-PRP) with use of intravascular deployment of adipose-derived cellular stromal vascular fraction (AD-cSVF)

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by Robert W Alexander, MD, Regeneris Medical:


Arthritis Degenerative Tendinosis Jont disease Low back pain

Additional relevant MeSH terms:

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Osteoarthritis Musculoskeletal Pain Tendinopathy Joint Diseases Rheumatoid Nodule Back Pain Arthritis Musculoskeletal Diseases	Rheumatic Diseases Pain Neurologic Manifestations Muscular Diseases Tendon Injuries Wounds and Injuries Arthritis, Rheumatoid Connective Tissue Diseases

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