Angiodysplastic BleedingEarly Phase 1NCT04811261
u-STOP LVAD Bleed: Utilization of Umbilical Cord Lining Stem Cells (ULSCs) To Prevent Left Ventricular Assist Device (LVAD) Associated Angiodysplastic Bleeding
A Early Phase 1 study testing Intravenous Infusion of UCLSCs in people with Angiodysplastic Bleeding, run by University of Florida at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Angiodysplastic Bleeding
- What is being tested?
- Intravenous Infusion of UCLSCs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2021to 27 Jul 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 20Show fewer
- 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 (<14 days) or active use of immunosuppressive drugs (including but not limited to high-dose corticosteroids [>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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- Angiodysplastic Bleeding
- Being tested
- Intravenous Infusion of UCLSCs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous Infusion of UCLSCsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 3+3 dose escalation | Experimental | The first 3 subjects' patients 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. Receives: Drug: Intravenous Infusion of UCLSCs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with Dose Limiting Toxicity (DLT) that begins during or following ULSC infusion
Dose Limiting Toxicities are treatment-emergent suspected adverse reactions graded severe, such as severe infusion-related hypersensitivity toxicities of grade ≥3, and any serious adverse event (SAE). (Note: DLT during an infusion will stop that infusion in that subject.)
Measured: Within 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2021
- Study start1 Nov 2021
- Primary completion27 Jul 2023
- Study completion27 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Angiodysplastic BleedingStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model 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.
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mustafa Ahmed, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04811261
- Sponsor's protocol ID
- u-STOP LVAD Bleed
- Other IDs
- IRB202100247, OCR40194
- Status last verified
- Aug 2023
- First submitted
- 19 Mar 2021
- Last updated
- 2 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ahmed MM, Meece LE, Handberg EM, Pepine CJ. Intravenous administration of umbilical cord lining stem cells in left ventricular assist device recipient: Rationale and design of the uSTOP LVAD BLEED pilot study. Am Heart J Plus. 2022 May 8;16:100142. doi: 10.1016/j.ahjo.2022.100142. eCollection 2022 Apr.
PubMed 38559284
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- u-STOP LVAD Bleed: Utilization of Umbilical Cord Lining Stem Cells (ULSCs) To Prevent Left Ventricular Assist Device (LVAD) Associated Angiodysplastic Bleeding
- ClinicalTrials.gov ID
- NCT04811261
- Acronym / sponsor ID
- u-STOP LVAD Bleed
- Conditions
- Angiodysplastic Bleeding
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 27 Jul 2023 (actual)
- Study completion
- 27 Jul 2023 (actual)
- First posted
- 23 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model 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.
| Arm | Type | Receives |
|---|---|---|
| 3+3 dose escalation | Experimental | Drug: Intravenous Infusion of UCLSCsThe first 3 subjects' patients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Infusion of UCLSCsThe 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. | Drug | 3+3 dose escalation |
Primary outcome
Number of Subjects with Dose Limiting Toxicity (DLT) that begins during or following ULSC infusion
Time frame: Within 24 hours
Dose Limiting Toxicities are treatment-emergent suspected adverse reactions graded severe, such as severe infusion-related hypersensitivity toxicities of grade ≥3, and any serious adverse event (SAE). (Note: DLT during an infusion will stop that infusion in that subject.)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2023.
- Derived from this study: PubMed 38559284Ahmed MM, Meece LE, Handberg EM, Pepine CJ. Intravenous administration of umbilical cord lining stem cells in left ventricular assist device recipient: Rationale and design of the uSTOP LVAD BLEED pilot study. Am Heart J Plus. 2022 May 8;16:100142. doi: 10.1016/j.ahjo.2022.100142. eCollection 2022 Apr.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mustafa Ahmed, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Intravenous Infusion of UCLSCs in people with Angiodysplastic Bleeding, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects with Dose Limiting Toxicity (DLT) that begins during or following ULSC infusion (time frame: Within 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04811261, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2023.