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u-STOP LVAD Bleed
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StatusAccepting Candidates
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Age18 Years - 80 Years
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SexesAll
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Healthy VolunteersNo
Objective
This is a Phase I, single ascending dose, first in human, open-label, non-controlled, dose-escalation trial that will investigate intravenous infusions of Umbilical cord lining stem cells (UCLSCs) in Left Ventricular Assist Device (LVAD) patients.
This study will recruit patients from the Advanced Heart Failure and LVAD Clinic at the University of Florida, including recently implanted patients, as well as patients on chronic long-term support, with the goal of enrolling up to 9 subjects to participate in the study.
Description
Subjects will be entered into a 3+3 dose escalation study, a standard design for initial trials to evaluate tolerability of a therapeutic agent and identify a maximal tolerated dose if indeed toxicities are identified in the pre-specified dosing range. The first 3 subjects will be administered 50 x 10^6 ULSCs reconstituted in PBS with 1% human serum albumin in a volume of 250 ml, and monitored for adverse events or toxicities, immediately following dosing, and again at 30 days. Safety endpoints will be reviewed by the DSMB and depending on the response, the dose will be escalated to 100 x 10^6 and 200 x 10^6 ULSC in a constant 250 ml volume. We will enroll only 9 subjects in the case that no subject experiences toxicity, only expanding the cohort in the event that a subject experiences toxicity at a particular dose.
This specific dose escalation approach is based on the following considerations:
There is not yet a standard dosing regimen for cell therapy in heart failure patients. The previous MSC trial in LVAD patients provided 150 million cells. The RIMECARD trial (Bartolucci et al, Circ Res 2017 Oct 27;121(10):1192-1204. PMID 28974553) provided umbilical cord-derived MSC for patients with heart failure via intravenous infusions of 1x106 cells/kg. Similarly, another Phase IIa trial of MSCs in HFrEF used 1.5x106 cells/kg (Butler et al., Circ Res 2017 Jan 20;120(2):332-340. PMID 27856497). Since our LVAD patients range in size from 50 to > 100kg, we believe the selected range of doses is reasonable for this patient population.
In addition, in ongoing studies in COVID 19 ARDS, IND# 19979, we have provided 100 x 106 ULSCs with no adverse safety signals. Moreover, in our non-clinical animal models, we demonstrated safety at doses ranging from a high dose of 1 x 106 cells/mouse, which is equivalent to approximately 5 x 107 cells/kg in humans and a low dose of 5 x 104 cells/mouse which is equivalent to approximately 2.5 x 106 cells/kg in humans. The dose tested in the high dose preclinical study would scale to administration of over 2.5 billion cells in an individual weighing 100 pounds.
Details
Full study title | u-STOP LVAD Bleed: Utilization of Umbilical Cord Lining Stem Cells (UCLSCs) To Prevent Left Ventricular Assist Device (LVAD) Associated Angiodysplastic Bleeding |
Protocol number | OCR40194 |
ClinicalTrials.gov ID | NCT04811261 |
Phase | Early Phase 1 |
Eligibility
Inclusion Criteria:
Be ≥ 18 years of age
Have heart failure with reduced ejection fraction and a durable centrifugal flow LVAD
Be on a stable regimen of heart failure medications for at least two weeks, including ACE/ARB/ARNi unless there is a documented contraindication to their use. These medications will be provided at an optimized, guideline-directed maximally tolerated dose.
Exclusion Criteria:
Durable Biventricular support
An axial flow LVAD
History of Crohn's Disease, Ulcerative Colitis, or other Inflammatory Bowel Disease on active treatment
LVAD implantation within the last 30 days
Anticipated need for non-cardiac surgery within the next 12 months
Evidence of active systemic infection at time of study product delivery
Evidence of infectious diseases such as hepatitis B, hepatitis C and HIV
Prior heart transplant recipients
Active cancer (or prior diagnosis of cancer within the past 2 years)
Recent (1 mg/kg of prednisone equivalent], TNF-α
blockers, cyclosporine) not including NSAIDs or corticosteroids used for IV dye
allergy only)
- Chronic auto-immune or auto-inflammatory disease (including but not limited to
rheumatoid arthritis, systemic lupus erythematosus)
- Recent or planned use of vaccination with live attenuated viruses within the next 30
days
Allergy to rubber or latex, or to DMSO.
Pregnancy or breastfeeding; fertile women must use contraception to avoid pregnancy.
Patient has known hypo* or hyper-coagulable state such as disseminated intravascular
coagulation and heparin induced thrombocytopenia (HIT)
Platelet count < 100K
Inability to maintain an INR of 2-3
Inability to give informed consent
Cognitive or language barriers that prohibit obtaining informed consent or any study
elements (interpreter permitted)
- Any other condition that, in the judgment of the Investigator, would be a
contraindication to enrollment, study product administration, or follow-up
Lead researcher
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Mustafa M Ahmed, MDCardiologist (Heart Specialist), Advanced Heart Failure and Transplant Specialist
Participate in a study
Here are some general steps to consider when participating in a research study:
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Step1
Contact the research team
Call or email the research team listed within the specific clinical trial or study to let them know that you're interested. A member of the research team, such as the researcher or study coordinator, will be available to tell you more about the study and to answer any questions or concerns you may have.
Primary contact
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Step2
Get screened to confirm eligibility
You may be asked to take part in prescreening to make sure you are eligible for a study. The prescreening process ensures it is safe for you to participate. During the prescreening process, you will be asked some questions and you may also be asked to schedule tests or procedures to confirm your eligibility.
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Step3
Provide your consent to participate
If you are eligible and want to join the clinical trial or study, a member of the research team will ask for your consent to participate. To give consent, you will be asked to read and sign a consent form for the study. This consent form explains the study's purpose, procedures, risks, benefits and provides other important information, such as the study team's contact information.
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Step4
Participate
If you decide to participate in a clinical trial or study, the research team will keep you informed of the study requirements and what you will need to do to throughout the study. For some trials or studies, your health care provider may work with the research team to ensure there are no conflicts with other medications or treatments.