A Phase 2 interventional study of Uncultured, autologous, adipose-derived regenerative cells (UA-ADRCs) and Continuation of patient's best guideline based medical treatment in Myocardial Injury, LV Dysfunction and Coronary Artery Disease, sponsored by Ralf Rothoerl. Recruiting at 1 site in Kazakhstan. Open to participants aged 21 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-12-03.
Sponsored by Ralf Rothoerl · Phase 2, Interventional, and Treatment
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.
The aim of the study is to investigate patients suffering from chronic congestive heart failure (iHF) and a left ventricular ejection fraction (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 uncultured, autologous, adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care. The cells will be isolated using the Transpose® RT / Matrase System (InGeneron, Houston, TX, USA) through an over-the-wire, small balloon catheter, advanced through the coronary sinus and located within a coronary vein at the site of interest, versus patients on best medical treatment.
This study hypothesizes that treatment of iHF with a balloon-enhanced i.cv. injection of UA-ADRCs isolated from lipoaspirate at the point of care using the Transpose RT / Matrase system (InGeneron) is safe and effective and is more effective than best medical treatment.
The primary objective of this study is to evaluate safety and efficacy of treating iHF with a single, balloon-enhanced retrograde i.cv. injection of UA-ADRCs. Efficacy will be demonstrated in a superiority study design by comparing improvement in global cardiac functional parameters demonstrated using cardiac magnetic resonance imaging (cMRI) or Cardiac CT, and by clinical endpoints after a single i.cv. injection of UA-ADRCs, to best medical treatment. Safety will be demonstrated by reporting major ad-verse cardiac events (MACE) and other adverse events.
A total of n=36 patients with iHF and a reduced LVEF (at ≤40%) will be randomly assigned to i.cv. injection of either UA-ADRCs (UA-ADRCs Group; n=24) or best medical treatment (Control Group; n=12). The enrollment will take place up to four study sites, among them the National Science Research Center of the Principal Investigator (Dr. Abay Baigenzhin) in Astana (Kazakhstan), will enroll 36 patients in the study. The study duration is the time to enroll patients in the study and will take 6 months. Individual follow-up time after the treatment is 6 months.
Follow-up schedule is as follows. Follow-up visits will take place at 1, 3, and 6 months post- treatment. Follow-up visit will include an assessment by cMRI, or cCT, physical examinations including echocardiography, patient-reported outcome questionnaires, control of medication usage, number of hospitalizations for cardiac conditions, and adverse event monitoring (including MACE). Those patients in the control group that have finished the 1, 3, and 6 month follow up visits will be offered to be treated with stem cell therapy as well. All remaining patients in both groups will be offered to participate in a subsequent registry study for 12 and 24-month follow-up vis-its, that could include physical examinations, patient-reported outcome questionnaires, medication usage, number of hospitalizations for cardiac conditions, and adverse event monitoring (including MACE) and cMRI or cCT. These long-term data would be compared to the corresponding baseline data.
The Primary Endpoint is to be cardiac function represented by left ventricular ejection fraction (LVEF) at 6 months assessed by cardiac MRI (cMRI) or cCT. Treatment success is defined as a 15% relative increase of LVEF from baseline to 6-month follow-up. Treatment success is expected in 65% of patients in the treatment group vs 10% in the control group. Secondary Endpoints will be assessed at baseline and at 6 months post-treatment and will include:
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.
Background Heart failure and myocardial infarction (MI) are consequences of ischemic heart disease (IHD) [1]. In recent years cell-based therapies have emerged as a promising strategy to re-generate ischemic myocardium [2-4]. However, the generally disappointing outcome of related clinical trials established a need for developing novel, more effective cell-based therapies for MI. In this regard, it is of note that the treatment of chronic MI (i.e., patients with a previous MI) (CMI) requires a different approach than the treatment of acute MI (AMI).
The amount of pluripotent stem cells has been reported to be significantly higher in adipose tissue than in bone marrow (5% to 10% vs. 0.1%) [12]. Fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) have the advantage over culture-expanded adipose-derived stem cells (ASCs) that UA-ADRCs allow for immediate usage at the point of care, combined with low safety concerns, since no culturing or modification is applied.
Several experimental studies in animal models have demonstrated the potential of UA-ADRCs for treating AMI [13-15], and a first clinical trial (APOLLO) showed promising preliminary results [16]. The investigators recently published results of a preclinical porcine study regarding the treatment of chronic ischemic heart failure (> 4 wk post-MI) with UA-ADRCs [28]. This study demonstrated that retrograde delivery of UA-ADRCs in a porcine model of chronic ischemic heart failure significantly improved myocardial function, increased myocardial mass, and reduced scar tissue formation. As part of this study, an evidence-based systematic review of the literature according to the PRISMA guidelines was conducted to examine preclinical studies on the treatment of iHF with stem cells [28].
Preliminary results from a study including 28 patients with chronic ischemic cardiomyopathy In one study evaluating the safety and preliminary efficacy of stromal vascular fraction ad-ministration (by a needle catheter into the myocardium) including 28 patients with chronic ischemic cardiomyopathy, the authors reported results from the six-minute walk test and LVEF at baseline and three and six months (with additional testing at 12 months if applicable) after treatment. LVEF increased from baseline to three and six months of follow-up. Results from a six-minute walk test showed a performance increase of about 80m from baseline to three, six, and twelve months of follow-up [18].
Results of our initial open-label Pilot Study in patients with inclusion and exclusion criteria comparable to the now designed randomized prospective study The pilot phase study for this randomized study was conducted in collaboration with the National Scientific Medical Center, Astana, Kazakhstan. Six patients were enrolled (five male, one female, NYHA class III, age 61.3±6.2 years) with the diagnosis of chronic ischemic heart failure and no improvement of symptoms or function after standard therapy for at least one month. All patients had documented coronary artery disease with evidence of myocardial injury and left ventricular dysfunction. Five out of six participants presented LVEF of ≤40%. All patients underwent liposuction under conscious sedation and local anesthesia. Lipoaspirate was processed according to the established InGeneron procedure to produce a cellular suspension of stromal vascular fraction including UA-ADRCs using the Transpose® RT / Matrase System (InGeneron, Houston, TX, USA). This cellular preparation was retrogradely injected via the coronary sinus into the corresponding coronary vein. The main outcome of interest was the change of LVEF (assessed by cMRI) from baseline to 3-6 months. In five of the six patients, an improvement in LVEF was observed. Further, adverse events reported were related to mild bruising/swelling/redness at the site of the liposuction in the abdominal area. There were no hospitalizations or health decline due to HF symptoms throughout the initial follow-up phase.
Rationale and Outcomes for Using UA-ADRCs
UA-ADRCs have several advantages over other types of cells used in and/or under investigation for regenerative cell therapy:
An optimal system for providing UA-ADRCs at the point of care should be capable of isolating the highest possible number of living ADRCs from the lowest possible amount of adipose tissue, in the shortest possible time, and providing the cells at the highest possible concentration in a final cell suspension. In this regard, it has been demonstrated in the literature that the Transpose RT / Matrase sys-tem (InGeneron, Houston, TX, USA) is the most efficient method with respect to the viable cell yield (i.e., the number of living cells / mL lipoaspirate).
Specifically, the investigators hypothesize that (i) a single i.cv injection of UA-ADRCs isolated with the Transpose RT / Matrase system (InGeneron) is safe and effective in the treatment of iHF, (ii) this therapy is statistically significantly more effective than just guideline based drug treatment, and (iii) i.cv injection of UA-ADRCs will possibly gain widespread acceptance, if safety and higher effectiveness than standard maximum drug therapy will be demonstrated by this and following multicenter randomized controlled trials.
260 studies on the registry are indexed under Ventricular Dysfunction, Left; 57 are open to participants now.
This study's planned enrollment of 36 is below the median of 100 across 151 interventional studies indexed under Ventricular Dysfunction, Left.
Browse Ventricular Dysfunction, Left studies →This is the only study on the registry with Ralf Rothoerl as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria
ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; CABG, coronary artery bypass grafting; CRT, cardiac resynchronization therapy; EF, ; eGFR, estimated glomerular filtration rate; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; ICD, implantable cardioverter defibrillator; INR, international normalized ratio; LV, left ventricular; MRI, magnetic resonance imaging; PCI, percutaneous coronary intervention; TNF-α, tumor necrosis factor-α; ULN, upper limit of normal; UNOS, United Network for Organ Sharing; and Vo2 max, maximal oxygen consumption.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
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
Intracardial venous injection of fresh, uncultured, autologous, adipose-derived regenerative cells isolated from lipoaspirate at the point of care.
Patients will receive continuation of their best guideline based medical treatment.
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.
Time frame: Baseline and at 6 month post-treatment
n-terminal pro-b-type natriuretic peptide
Assessment of n-terminal pro-b-type natriuretic peptide in the blood samples of the patients.
Time frame: Baseline and at 6 month post-treatment
6-min walk test
A validated, sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.
Time frame: Baseline and at 6 month post-treatment
Scar tissue assessment only in patients with cMRI
Only in patients with cMRI: relative amount of left ventricular scar tissue, left ventricular bull's eye segmental contracting areas.
Time frame: Baseline and at 6 month post-treatment
The Minnesota Living with Heart Failure Questionnaire (MLHFQ) score
The Minnesota Living with Heart Failure Questionnaire (MLHFQ) Total score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of lifescore will be applied to the patients.
Time frame: Baseline and at 6 month post-treatment
New York Heart Association (NYHA) class
Assessment of cardiac function according to New York Heart Association (NYHA) class.
Time frame: Baseline and at 6 month post-treatment
Incidence of treatment-related adverse events (including MACE)
Consists of the reported composite of total death; MI; stroke, hospitalization because of HF; and revascularization, including percutaneous coronary intervention, and coronary artery bypass graft.
Time frame: Baseline and at 6 month post-treatment
Plan to share: Undecided — too early
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