Clinical trial NCT03090672: Cellular & Biocellular Regenerative Therapy in Musculoskeletal Pain, Dysfunction,Degenerative or Inflammatory Disease
Official title: Use of Cellular and Biocellular Therapy in Musculoskeletal Pain, Dysfunction, Degenerative or Inflammatory Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Osteoarthritis
Rheumatoid Nodule
Degenerative Joint Disease
Tendinopathy
Tendinosis
Back Pain
Keywords: Arthritis
Degenerative
Tendinosis
Jont disease
Low back pain
Lead sponsor: Regeneris Medical
Sponsor class: OTHER
Collaborators: name: Regeneris Medical
name: Global Alliance for Regenerative Medicine
First posted: 2017-03-27
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Participants with complications
timeFrame: 1 month
Secondary outcomes:
measure: Change from baseline quality of life level (QoL Questionnaire)
timeFrame: 6 months, 12 months
measure: Change from baseline visual analog pain score
timeFrame: 6 months, 1 year, 2 year
measure: Change from baseline of limitation of activities (Functional analysis of range of motion)
timeFrame: baseline, 6 months, 1 year
measure: Change from baseline of imaging if required for study entry
timeFrame: baseline, 1 year
Other outcomes:
Locations:
city: North Attleboro
country: United States
facility: Regeneris Medical
state: Massachusetts
city: North Attleboro
country: United States
facility: Regeneris Medical
state: Massachusetts
Study officials:
affiliation: GARM USA
name: Robert W Alexander, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Global Alliance for Regenerative Medicine (GARM)
name: Glenn C Terry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regeneris Medical
name: Ryan JP Welter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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