Study to Assess Safety and Efficacy of Treating Symptomatic, Ischemic, Chronic Congestive Heart Failure Patients with an LVEF of ≤40% with Fresh, Uncultured, Autologous, Adipose-derived Regenerative Cells Isolated from Lipoaspirate.

NCT06705023 | Recruiting Phase 2

• 1 other identifier: 001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate patients suffering from iHF and a LVEF of equal or less than 40% despite best medical treatment safety and efficacy of a single retrograde intra-cardiac venous (i.cv.) injection of UA-ADRCs isolated from lipoaspirate at the point of care, using the Transpose® RT / Matrase System (InGeneron, Houston, TX, USA) through an over-the- wire, small balloon catheter, advanced through the coronary si-nus and located within a coronary vein at the site of inter-est, versus patients on best medical treatment.

Conditions

Myocardial Injury; LV Dysfunction; Coronary Artery Disease; Heart Failure

Keywords

congestive heart failure; adipose-derived regenerative cells; left ventricular ejection fraction; lipoaspirate; retrograde intra-cardiac venous injection; Cardiac Magnetic Resonance Imaging; Cardiac Computer Tomography; end systolic volume; end diastolic volume

Outcome Measures

Primary Outcomes (1)

• Left ventricular ejection fraction at 6 months assessed by cardiac MRI or cCT

  Change / Increase in cardiac function (LVEF from baseline to 6 month follow-up). Treatment success is defined as ≥15% increase in LVEF assessed by cMRI or cCT if cMRI is not feasible.

  Baseline and at 6 month post-treatment

Secondary Outcomes (6)

• n-terminal pro-b-type natriuretic peptide

  Baseline and at 6 month post-treatment

• 6-min walk test

  Baseline and at 6 month post-treatment

• Scar tissue assessment only in patients with cMRI

  Baseline and at 6 month post-treatment

• The Minnesota Living with Heart Failure Questionnaire (MLHFQ) score

  Baseline and at 6 month post-treatment

• New York Heart Association (NYHA) class

  Baseline and at 6 month post-treatment

Study Arms (2)

UA-ADRCs group

EXPERIMENTAL

Patients in the UA-ADRC (uncultured, autologous, adipose-derived regenerative cells) group will be treated as follows: 1. Patients will have an outpatient liposuction procedure from the abdomen, bilateral flanks, and/or medial thigh (at least 100 mL of adipose tissue) to get cell product. 2. Oral sedation and local anesthesia with tumescent solution will be used. Patients' vitals will be monitored and recorded during the procedure and in 1 to 2 hours post-procedure. 3. Each patient in the UA-ADRC group will have cells isolated using the Transpose RT/Matrase system (InGeneron). 4. Cell product testing will be assessed with the following acceptance criteria: total nucleated cell count is \> 35 million cells, b) cell viability is \> 75%. AE status will be monitored for 30 days post-liposuction procedure. 5. The i.cv injection of UA-ADRCs will be given using an aseptic technique. This group will include 24 patients.

Biological: Uncultured, autologous, adipose-derived regenerative cells (UA-ADRCs)

Control group

ACTIVE COMPARATOR

Patients will receive continuation of their best guideline based medical treatment. This group will include 12 patients.

Other: Continuation of patient's best guideline based medical treatment

Interventions

Uncultured, autologous, adipose-derived regenerative cells (UA-ADRCs) BIOLOGICAL

Intracardial venous injection of fresh, uncultured, autologous, adipose-derived regenerative cells isolated from lipoaspirate at the point of care.

UA-ADRCs group

Continuation of patient's best guideline based medical treatment OTHER

Patients will receive continuation of their best guideline based medical treatment.

Control group

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have documented coronary artery disease with evidence of myocardial injury, LV dysfunction, and clinical evidence of heart failure
• Have an EF ≤40% by cardiac MRI
• Be receiving guideline-driven medical therapy for heart failure at stable and tolerated doses for ≥1 month before consent
• Be a candidate for right heart cardiac catheterization
• Have New York Heart Association class I, II, or III heart failure symptoms
• If a female of childbearing potential, be willing to use one form of birth control for the duration of the study, and undergo a pregnancy test at baseline and within 36 h before treatment

You may not qualify if:

• Indication for standard-of-care surgery (including valve surgery, placement of LV assist device, or imminent heart transplantation), CABG procedure, and PCI. Candidates cannot be UNOS 1A or 1B, and they must have documented low probability of being transplanted.
• PCI within 3 months of randomization
• CABG within 3 months of randomization
• Valvular heart disease including mechanical or bioprosthetic heart valve, severe valvular (any valve) insufficiency/regurgitation within 12 month of consent, and aortic stenosis with valve area ≤1.5 cm2
• History of ischemic or hemorrhagic stroke within 90 d of consent
• History of an LV remodeling surgical procedure utilizing prosthetic material
• Presence of a pacemaker and ICD generator with any of the following limitations/conditions: manufactured before the year 2015
• Leads implanted \<6 week before consent
• Non-transvenous epicardial or abandoned leads
• Subcutaneous ICDs
• Leadless pacemakers
• Pacemaker-dependence with an ICD (pacemaker-dependent candidates without an ICD are not excluded)
• Any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated
• A CRT device implanted within 3 months of consent
• An appropriate ICD firing or antitachycardia pacing for ventricular fibrillation or ventricular tachycardia within 30 days of consent

Sponsors & Collaborators

• Ralf Rothoerl: lead
• National Scientific Medical Center, Kazakhstan: collaborator
• Internationnal Foundation Medicine and Science: collaborator
• Alliance of Cardiovascular Researchers: collaborator

Study Sites (1)

National Scientific Medical Center

Astana, 010009, Kazakhstan

RECRUITING

Related Publications (17)

• Anderson JL, Morrow DA. Acute Myocardial Infarction. N Engl J Med. 2017 May 25;376(21):2053-2064. doi: 10.1056/NEJMra1606915. No abstract available.

  PMID: 28538121 BACKGROUND

• Ma T, Sun J, Zhao Z, Lei W, Chen Y, Wang X, Yang J, Shen Z. A brief review: adipose-derived stem cells and their therapeutic potential in cardiovascular diseases. Stem Cell Res Ther. 2017 Jun 5;8(1):124. doi: 10.1186/s13287-017-0585-3.

  PMID: 28583198 BACKGROUND

• Yu H, Lu K, Zhu J, Wang J. Stem cell therapy for ischemic heart diseases. Br Med Bull. 2017 Jan 1;121(1):135-154. doi: 10.1093/bmb/ldw059.

  PMID: 28164211 BACKGROUND

• Alt E, Pinkernell K, Scharlau M, Coleman M, Fotuhi P, Nabzdyk C, Matthias N, Gehmert S, Song YH. Effect of freshly isolated autologous tissue resident stromal cells on cardiac function and perfusion following acute myocardial infarction. Int J Cardiol. 2010 Sep 24;144(1):26-35. doi: 10.1016/j.ijcard.2009.03.124. Epub 2009 May 13.

  PMID: 19443059 BACKGROUND

• van Dijk A, Naaijkens BA, Jurgens WJ, Nalliah K, Sairras S, van der Pijl RJ, Vo K, Vonk AB, van Rossum AC, Paulus WJ, van Milligen FJ, Niessen HW. Reduction of infarct size by intravenous injection of uncultured adipose derived stromal cells in a rat model is dependent on the time point of application. Stem Cell Res. 2011 Nov;7(3):219-29. doi: 10.1016/j.scr.2011.06.003. Epub 2011 Jun 25.

  PMID: 21907165 BACKGROUND

• Houtgraaf JH, den Dekker WK, van Dalen BM, Springeling T, de Jong R, van Geuns RJ, Geleijnse ML, Fernandez-Aviles F, Zijlsta F, Serruys PW, Duckers HJ. First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2012 Jan 31;59(5):539-40. doi: 10.1016/j.jacc.2011.09.065. No abstract available.

  PMID: 22281257 BACKGROUND

• Comella K, Parcero J, Bansal H, Perez J, Lopez J, Agrawal A, Ichim T. Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy. J Transl Med. 2016 Jun 2;14(1):158. doi: 10.1186/s12967-016-0918-5.

  PMID: 27255774 BACKGROUND

• Swijnenburg RJ, Tanaka M, Vogel H, Baker J, Kofidis T, Gunawan F, Lebl DR, Caffarelli AD, de Bruin JL, Fedoseyeva EV, Robbins RC. Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation. 2005 Aug 30;112(9 Suppl):I166-72. doi: 10.1161/CIRCULATIONAHA.104.525824.

  PMID: 16159810 BACKGROUND

• Zhang Y, Wang D, Chen M, Yang B, Zhang F, Cao K. Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart. PLoS One. 2011 Apr 28;6(4):e19012. doi: 10.1371/journal.pone.0019012.

  PMID: 21552563 BACKGROUND

• Trounson A. Potential Pitfall of Pluripotent Stem Cells. N Engl J Med. 2017 Aug 3;377(5):490-491. doi: 10.1056/NEJMcibr1706906. No abstract available.

  PMID: 28767348 BACKGROUND

• Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 2006 Apr;24(4):150-4. doi: 10.1016/j.tibtech.2006.01.010. Epub 2006 Feb 20.

  PMID: 16488036 BACKGROUND

• Ong WK, Sugii S. Adipose-derived stem cells: fatty potentials for therapy. Int J Biochem Cell Biol. 2013 Jun;45(6):1083-6. doi: 10.1016/j.biocel.2013.02.013. Epub 2013 Mar 1.

  PMID: 23458962 BACKGROUND

• Klein SM, Vykoukal J, Li DP, Pan HL, Zeitler K, Alt E, Geis S, Felthaus O, Prantl L. Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue-Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration-Approved Nerve Conduit. Plast Reconstr Surg. 2016 Jul;138(1):132-139. doi: 10.1097/PRS.0000000000002291.

  PMID: 27348645 BACKGROUND

• Jiang T, Xu G, Wang Q, Yang L, Zheng L, Zhao J, Zhang X. In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects. Cell Death Dis. 2017 Jun 1;8(6):e2851. doi: 10.1038/cddis.2017.215.

  PMID: 28569773 BACKGROUND

• Sheu JJ, Lee MS, Wallace CG, Chen KH, Sung PH, Chua S, Lee FY, Chung SY, Chen YL, Li YC, Yip HK. Therapeutic effects of adipose derived fresh stromal vascular fraction-containing stem cells versus cultured adipose derived mesenchymal stem cells on rescuing heart function in rat after acute myocardial infarction. Am J Transl Res. 2019 Jan 15;11(1):67-86. eCollection 2019.

  PMID: 30787970 BACKGROUND

• Nyberg E, Farris A, O'Sullivan A, Rodriguez R, Grayson W. Comparison of Stromal Vascular Fraction and Passaged Adipose-Derived Stromal/Stem Cells as Point-of-Care Agents for Bone Regeneration. Tissue Eng Part A. 2019 Nov;25(21-22):1459-1469. doi: 10.1089/ten.TEA.2018.0341. Epub 2019 Jun 14.

  PMID: 30734661 BACKGROUND

• Polly SS, Nichols AEC, Donnini E, Inman DJ, Scott TJ, Apple SM, Werre SR, Dahlgren LA. Adipose-Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing. J Orthop Res. 2019 Jun;37(6):1429-1439. doi: 10.1002/jor.24307. Epub 2019 Apr 29.

  PMID: 30977556 BACKGROUND

MeSH Terms

Conditions

Ventricular Dysfunction, Left; Coronary Artery Disease; Heart Failure

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Abay Baigenzhin, Prof Dr

  National Scientific Medical Center

  PRINCIPAL INVESTIGATOR

• Ralf Rothoerl, Dr

  International Foundation of Medicine and Science

  STUDY DIRECTOR

Central Study Contacts

Anastassiya Ganina-Smelova, PhD

CONTACT

+77024346421; anastassiya_smelova@mail.ru

Aizhan Akhaeva, PhD

CONTACT

+77075008522; akhaeva@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: coordinator

Model Details: This is a prospective, randomized, controlled, multicenter, safety and efficacy study in patients with iHF comparing best available medical treatment plus a balloon-enhanced single i.cv. injection of UA-ADRCs isolated from lipoaspirate at point of care using the Transpose RT / Matrase system (InGeneron) in 24 patients, to best available medical treatment in 12 patients in the control group

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: November 26, 2024
• Study Start: November 18, 2024
• Primary Completion: October 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Locations

KA (1)