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

NCT ID: NCT03090672

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-11
• Study Completion Date: 2022-12-31

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.

Detailed Description

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 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.

Conditions

Osteoarthritis; Rheumatoid Nodule; Degenerative Joint Disease; Tendinopathy; Tendinosis; Back Pain

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

tSVF + PRP Arm1

Stromal Vascular Fraction tSVF + Platelet Rich Plasma (PRP) concentrate

Group Type: EXPERIMENTAL

Tissue Stromal Vascular Fraction

Intervention Type: PROCEDURE

tSVF

Platelet Rich Plasma

Intervention Type: BIOLOGICAL

PRP

tSVF + PRP + cSVF Enrichment Arm 2

tissue Stromal Vascular Fraction (tSVF) + Platelet-Rich Plasma (PRP) concentration + (cSVF)

Group Type: EXPERIMENTAL

Tissue Stromal Vascular Fraction

Intervention Type: PROCEDURE

tSVF

Platelet Rich Plasma

Intervention Type: BIOLOGICAL

PRP

Cellular Stromal Vascular Fraction

Intervention Type: PROCEDURE

cSVF

Normal Saline IV + cSVF Arm 3

Cellular Stromal Vascular Fraction (cSVF); Normal Saline IV introduction

Group Type: EXPERIMENTAL

Normal Saline

Intervention Type: DRUG

Normal Saline IV delivery

Cellular Stromal Vascular Fraction

Intervention Type: PROCEDURE

cSVF

Interventions

Normal Saline

Normal Saline IV delivery

Intervention Type: DRUG

Tissue Stromal Vascular Fraction

tSVF

Intervention Type: PROCEDURE

Platelet Rich Plasma

PRP

Intervention Type: BIOLOGICAL

Cellular Stromal Vascular Fraction

cSVF

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneris Medical

OTHER

Sponsor Role: collaborator

Global Alliance for Regenerative Medicine

OTHER

Sponsor Role: collaborator

Robert W Alexander, MD

OTHER

Sponsor Role: lead

Responsible Party

Robert W Alexander, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert W Alexander, MD

Role: PRINCIPAL_INVESTIGATOR

GARM USA

Glenn C Terry, MD

Role: PRINCIPAL_INVESTIGATOR

Global Alliance for Regenerative Medicine (GARM)

Ryan JP Welter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Regeneris Medical

Locations

Regeneris Medical

North Attleboro, Massachusetts, United States

Site Status: RECRUITING

Regeneris Medical

North Attleboro, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ryan JP Welter, MD, PhD

Role: CONTACT

r.welter@regenerismedical.com

508.345.5492

Gabrielle Lewis

Role: CONTACT

g.lewis@regenerismedical.com

508.316.4268

Facility Contacts

Gabrielle Lewis

Role: primary

g.lewis@regenerismedical.com

508-316-4268

Gabielle lEWIS

Role: backup

g.lewis@regenerismedical.com

508/316.4268

Ryan JP Welter, MD

Role: primary

r.welter@regenerismedical.com

508-345-5492

Gabrielle Lewis

Role: backup

g.lewis@regenerismedical.com

508.316.4268

References

Kuorinka I, Jonsson B, Kilbom A, Vinterberg H, Biering-Sorensen F, Andersson G, Jorgensen K. Standardised Nordic questionnaires for the analysis of musculoskeletal symptoms. Appl Ergon. 1987 Sep;18(3):233-7. doi: 10.1016/0003-6870(87)90010-x.

Reference Type: BACKGROUND

PMID: 15676628 (View on PubMed)

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. doi: 10.1177/0018720812449648.

Reference Type: BACKGROUND

PMID: 23516797 (View on PubMed)

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 27788905 (View on PubMed)

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

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 23630430 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24387819 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24792949 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26080045 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22925619 (View on PubMed)

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.

Reference Type: RESULT

Other Identifiers

RGV MSK 1

Identifier Type: -

Identifier Source: org_study_id