Autologous Stem/Stromal Cellular Stromal Vascular Fraction (cSVF) In Frailty-Aging Processes

NCT03514537 | Suspended DMC FDA Device

• 1 other identifier: GARM-Frailty
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

With increasing age and health issues associated with aging, many systemic cellular and structural changes are known to occur. The intent of this trial is to determine the safety and efficacy of delivery of autologous cellular stromal vascular fraction (cSVF) to improve the quality of life and functional health. Isolation and concentration of cSVF will be documented. To acquire autologous cSVF, a 10+ teaspoon volume of subdermal adipose (fat) tissue and stroma is removed from the trunk or upper thigh area. Using a closed system with enzymatic digestion to isolate and concentrate these cells, is followed with returning these cSVF elements only via 500 cc Normal Saline delivered via peripheral vein (IV). Documentation of cellular numbers and flow cytometer viability testing is to be correlated with clinical outcomes as reported by patients and standardized Quality of Life (QoL) form tracking

Conditions

Frail Elderly Syndrome; Aging; Degenerative Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Number of Participants with Treatment Related Adverse \& Severe Adverse Events Assessed By CTCAE v4.0

  6 months

Secondary Outcomes (5)

• Changes in Weight In Pounds

  Baseline and 6 months

• Activity Level

  baseline and 6 months

• Mobility

  baseline and 6 months

• Fatigue

  baseline and 6 months

• Mobility Performance Battery

  baseline and 6 months

Study Arms (3)

Lipoaspiration

EXPERIMENTAL

Closed microcannula harvesting of small volume of subdermal adipose tissue, including the stromal cellular and stromal tissue using sterile, disposable, microcannula system

Procedure: Microcannula harvest adipose stromal tissues

Isolation & Concentration of cSVF

EXPERIMENTAL

Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocols

Device: Centricyte 1000; Drug: Liberase

Delivery cSVF via Intravenous

EXPERIMENTAL

cSVF from Arm 2 is suspended in a 500cc of sterile Normal Saline and deployed through 150 micron in-line filtration and intravenous route over 30-60 minute time frame.

Procedure: Sterile Normal Saline IV Deployment of cSVF; Drug: Saline Solution

Interventions

Microcannula harvest adipose stromal tissues PROCEDURE

Use of disposable, closed syringe microcannula harvest autologous adipose stroma and stem/stromal cells

Lipoaspiration

Centricyte 1000 DEVICE

Centricyte 1000, closed system digestion of stromal vascular fraction to isolate and concentrate stem/stromal cells associated with microvasculature

Isolation & Concentration of cSVF

Sterile Normal Saline IV Deployment of cSVF PROCEDURE

Sterile Normal Saline Suspension cSVF in 500 cc for Intravenous Delivery including 150 micron in-line filtration

Delivery cSVF via Intravenous

Liberase DRUG

Liberase TM for use to enzymatically isolate cellular stromal vascular fraction

Isolation & Concentration of cSVF

Saline Solution DRUG

Sterile, Normal Saline 500 for Intravenous use

Delivery cSVF via Intravenous

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be \>40 and \<90 years of age and willing and able to provide written informed consent
• Those aging and frail patients who have noted compromise to activities or work requirements due to increasing age
• Ability to execute a 6 minute walk test distance of \>200 meters and \<1000 meters
• Loss of energy and exercise tolerance over 6 month period minimum
• Current clinical history of malignancy within 3 years, except for curable skin lesions including basal cell carcinoma, or squamous cell carcinoma
• Must have the ability to provide Informed Consent

You may not qualify if:

• Medical conditions which prevent the ability of assessment of walk distance testing criteria
• Have disabling neurodegenerative disorder which would impede interpretation of outcomes
• Have a score of \<24 on the Mini Mental State Examination (MMSE)
• History of malignancy within 2 years (excluding curative skin lesion of basal cell carcinoma, melanoma-in-situ, or cervical carcinoma
• Have clinically important abnormal screening laboratory values, including, but not limited to: Hemoglobin \<10 g/dL; White blood cell count (WBC) \<2500/mL; Platelet count microliters \<100000/uL(microliters); Genetic Coagulopathy history
• Uncontrollable hypertension
• Systemic disorders that preclude completion of the testing or out of medical management control in the opinion of the PIs or Primary Care Provider
• Expected lifespan of less that 6 months
• Current drug abuse history \< 6 months
• Alcohol abuse within 6 months of enrollment
• Serious or life threatening co-morbidities that in the opinion of investigators, may compromise the safety or compliance with the study guidelines and tracking.

Sponsors & Collaborators

• Healeon Medical Inc: lead
• Micheal Nissenbaum, MD: collaborator
• Terry, Glenn C., M.D.: collaborator

Study Sites (1)

Fanny Island Campus Medical Building

Colchester, Vermont, 05446, United States

Location

Related Publications (33)

• Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, Ershler WB, Harris T, Fried LP. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc. 2006 Jun;54(6):991-1001. doi: 10.1111/j.1532-5415.2006.00745.x.

  PMID: 16776798 BACKGROUND

• Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. Epub 2013 Feb 8.

  PMID: 23395245 BACKGROUND

• Song X, Mitnitski A, Rockwood K. Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc. 2010 Apr;58(4):681-7. doi: 10.1111/j.1532-5415.2010.02764.x. Epub 2010 Mar 22.

  PMID: 20345864 BACKGROUND

• Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039.

  PMID: 23746838 BACKGROUND

• Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 2011 Feb;27(1):17-26. doi: 10.1016/j.cger.2010.08.008.

  PMID: 21093719 BACKGROUND

• Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med. 2011 Feb;27(1):1-15. doi: 10.1016/j.cger.2010.08.009.

  PMID: 21093718 BACKGROUND

• Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137.

  PMID: 28977399 BACKGROUND

• Peffers MJ, Collins J, Loughlin J, Proctor C, Clegg PD. A proteomic analysis of chondrogenic, osteogenic and tenogenic constructs from ageing mesenchymal stem cells. Stem Cell Res Ther. 2016 Sep 14;7(1):133. doi: 10.1186/s13287-016-0384-2.

  PMID: 27624072 BACKGROUND

• Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006 Feb;5(1):91-116. doi: 10.1016/j.arr.2005.10.001. Epub 2005 Nov 28.

  PMID: 16310414 BACKGROUND

• Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008 Mar;129(3):163-73. doi: 10.1016/j.mad.2007.12.002. Epub 2007 Dec 17.

  PMID: 18241911 BACKGROUND

• Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, Heldman AW, Miki R, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Pujol MV, Da Fonseca M, Oliva AA Jr, Green G, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Goldschmidt-Clermont PJ, Hare JM. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1505-1512. doi: 10.1093/gerona/glx056.

  PMID: 28444181 BACKGROUND

• Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, Denktas AE, Gammon RS, Hermiller JB Jr, Reisman MA, Schaer GL, Sherman W. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86. doi: 10.1016/j.jacc.2009.06.055.

  PMID: 19958962 BACKGROUND

• Hare JM, DiFede DL, Rieger AC, Florea V, Landin AM, El-Khorazaty J, Khan A, Mushtaq M, Lowery MH, Byrnes JJ, Hendel RC, Cohen MG, Alfonso CE, Valasaki K, Pujol MV, Golpanian S, Ghersin E, Fishman JE, Pattany P, Gomes SA, Delgado C, Miki R, Abuzeid F, Vidro-Casiano M, Premer C, Medina A, Porras V, Hatzistergos KE, Anderson E, Mendizabal A, Mitrani R, Heldman AW. Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017 Feb 7;69(5):526-537. doi: 10.1016/j.jacc.2016.11.009. Epub 2016 Nov 14.

  PMID: 27856208 BACKGROUND

• Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013 Jun;143(6):1590-1598. doi: 10.1378/chest.12-2094.

  PMID: 23172272 BACKGROUND

• Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015 Apr 10;116(8):1413-30. doi: 10.1161/CIRCRESAHA.116.303614.

  PMID: 25858066 BACKGROUND

• Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 30;173(5):489-95. doi: 10.1503/cmaj.050051.

  PMID: 16129869 BACKGROUND

• Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, Schulman IH, Longsomboon B, Wolf A, Khan A, Heldman AW, Goldschmidt-Clermont PJ, Hare JM. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.

  PMID: 26933813 BACKGROUND

• McElhaney JE, Effros RB. Immunosenescence: what does it mean to health outcomes in older adults? Curr Opin Immunol. 2009 Aug;21(4):418-24. doi: 10.1016/j.coi.2009.05.023. Epub 2009 Jun 29.

  PMID: 19570667 BACKGROUND

• Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, Sadamoto K, Yokoyama A, Yamanaka T, Onodera R, Kuroda A, Baba R, Kaneko Y, Tsukie T, Kurimoto Y, Okada Y, Kihara Y, Morioka S, Fukushima M, Asahara T. Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells. 2009 Nov;27(11):2857-64. doi: 10.1002/stem.207.

  PMID: 19711453 BACKGROUND

• Golpanian S, Schulman IH, Ebert RF, Heldman AW, DiFede DL, Yang PC, Wu JC, Bolli R, Perin EC, Moye L, Simari RD, Wolf A, Hare JM; Cardiovascular Cell Therapy Research Network. Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease. Stem Cells Transl Med. 2016 Feb;5(2):186-91. doi: 10.5966/sctm.2015-0101. Epub 2015 Dec 18.

  PMID: 26683870 BACKGROUND

• Schuleri KH, Feigenbaum GS, Centola M, Weiss ES, Zimmet JM, Turney J, Kellner J, Zviman MM, Hatzistergos KE, Detrick B, Conte JV, McNiece I, Steenbergen C, Lardo AC, Hare JM. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J. 2009 Nov;30(22):2722-32. doi: 10.1093/eurheartj/ehp265. Epub 2009 Jul 8.

  PMID: 19586959 BACKGROUND

• Siddiqi S, Sussman MA. Cell and gene therapy for severe heart failure patients: the time and place for Pim-1 kinase. Expert Rev Cardiovasc Ther. 2013 Aug;11(8):949-57. doi: 10.1586/14779072.2013.814830.

  PMID: 23984924 BACKGROUND

• ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.

  PMID: 12091180 BACKGROUND

• Enright PL, McBurnie MA, Bittner V, Tracy RP, McNamara R, Arnold A, Newman AB; Cardiovascular Health Study. The 6-min walk test: a quick measure of functional status in elderly adults. Chest. 2003 Feb;123(2):387-98. doi: 10.1378/chest.123.2.387.

  PMID: 12576356 BACKGROUND

• Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, Ritter PL. CHAMPS physical activity questionnaire for older adults: outcomes for interventions. Med Sci Sports Exerc. 2001 Jul;33(7):1126-41. doi: 10.1097/00005768-200107000-00010.

  PMID: 11445760 BACKGROUND

• Golpanian S, Wolf A, Hatzistergos KE, Hare JM. Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue. Physiol Rev. 2016 Jul;96(3):1127-68. doi: 10.1152/physrev.00019.2015.

  PMID: 27335447 BACKGROUND

• Rando TA, Wyss-Coray T. Stem cells as vehicles for youthful regeneration of aged tissues. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1(Suppl 1):S39-42. doi: 10.1093/gerona/glu043.

  PMID: 24833585 BACKGROUND

• Raggi C, Berardi AC. Mesenchymal stem cells, aging and regenerative medicine. Muscles Ligaments Tendons J. 2012 Oct 16;2(3):239-42. Print 2012 Jul.

  PMID: 23738303 BACKGROUND

• Tetta C, Consiglio AL, Bruno S, Tetta E, Gatti E, Dobreva M, Cremonesi F, Camussi G. The role of microvesicles derived from mesenchymal stem cells in tissue regeneration; a dream for tendon repair? Muscles Ligaments Tendons J. 2012 Oct 16;2(3):212-21. Print 2012 Jul.

  PMID: 23738299 BACKGROUND

• Alexander, R. Understanding Adipose-derived Stromal Vascular Fraction (AD-SVF) Cell Biology and Use on the Basis of Cellular, Chemical, Structural and Paracrine Components: A Concise Review. J Prolotherapy, 2012 J of Prolo (JOP) 4:e13777

  BACKGROUND

• Alexander, R., Understanding Mechanical Emulsification (Nanofat) Versus Enzymatic Isolation of Tissue Stromal Vascular Fraction (tSVF) Cells from Adipose Tissue: Potential Uses in Biocellular Regenerative Medicine Understanding J prolo 2016

  BACKGROUND

• ALEXANDER, ROBERT W., "Biocellular Regenerative Medicine: Adipose-Derived Stem/Stromal Cells & Matrix" . World Biomedical Frontiers, Section of Stem Cells, 2017 July. http://biomedfrontiers.org/stem-cells-2017-7-1.

  BACKGROUND

• ALEXANDER, ROBERT W., "Use of Microcannula Close Syringe System For Safe And Effective Lipoaspiration and Small Volume Autologous Fat Grafting", Am J Cosm Surg 2013, 30(2): 1-12

  BACKGROUND

MeSH Terms

Interventions

Liberase; Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Michael Nissenbaum, MD

  Healeon Medical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: May 2, 2018
• Study Start: March 15, 2018
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): January 15, 2028
• Last Updated: September 12, 2025

Record last verified: 2025-03

Locations

US (1)