Heart FailurePhase 1/2ASSURANCENCT00869024
Stem Cell Therapy in Patients With Severe Heart Failure & Undergoing Left Ventricular Assist Device Placement
A Phase 1/2 study testing Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells in people with Heart Failure, run by University of Minnesota at 1 site in United States.
Trial summary
The purpose of this study is to determine if the delivery of cells just after implantation of left ventricular assist device will help to improve the pumping function of your heart and minimize heart enlargement in the future. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2011to 29 Mar 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Severe LV dysfunction with EF < 30% with cardiomyopathy ( Ischemic and non ischemic)
- NYHA Class III and IV
- No revascularization options available
- LVAD placement as destination therapy or bridging to transplantation
- Age between 18-80 years
Who cannot join
- History of recent malignancy( less than one year) .
- Unstable hemodynamics at the time of the implant; defined by need for increasing vasopressor medication in the last 24 hours or blood pressure < 70 systolic, or cardiac index < 1.3 liters/min.
- Coronary anatomy suitable for revascularization at the time of surgery
- Pregnancy confirmed by positive urine test
- Lactating mothers
- Renal failure with serum creatinine >3.0, or are receiving chronic dialysis support.
Show all 11Show fewer
- Inability to undergo PET/CT imaging.
- A history of any significant recent bleeding disorder or coagulation profile of concern for acute bleeding, such as INR >2.0 (not on anticoagulant), platelet count <100,000, or hemoglobin <8.0 gr/dl.
- Patients with known infectious disease (Hepatitis, HIV) etc.
- Patients with three times or more of the upper limits of normal enzymes.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: AsseSsment of Efficacy, Safety and Utility of intRa myocardiAl iNjection of Stem Cells in Patients With End Stage Heart Failure Undergoing LVAD Implantation (ASSURANCE)
The purpose of this study is to determine if the delivery of cells just after implantation of left ventricular assist device will help to improve the pumping function of your heart and minimize heart enlargement in the future.
The cells will be obtained by aspiration or withdrawal of fluid from your bone marrow from your pelvic bone using a needle and syringe. This would not take place until 24-48 hours prior to your planned left ventricular assist device implantation. During the surgery the surgeons will inject the prepared cells that were taken from your bone marrow and inject it into your heart muscle.
This study will test whether receiving your own bone marrow cells directly into your heart will help your heart to recover function after placement of a left ventricular assist device.
Read the detailed description
Patients who meet the inclusion and exclusion criteria and agree to participate will be enrolled in the study. All the patients will have a baseline EKG, Laboratory tests, 2D ECHO and PET/CT imaging.Day prior to the LVAD implantation all the patients will undergo bone marrow aspiration. Bone marrow aspirate will be processed according to the protocols used by that facility. After processing, the bone marrow mononuclear cells will then be suspended in 2ml of 5% human serum albumin and labeled per the standard protocol of the facility.
Patients will be randomized in a 2:1 fashion either to receive cells or 5% serum albumin. Under general anesthesia using the standard techniques the HeartMate II (LVAD) will be placed. The LVAD will be inserted into the LV apex (with removal of 2 x 2 cm ventricular core). The tissue core will be processed for RNA isolation and morphological analysis. CV surgeon will inject either the cells or placebo directly in to the myocardium in the LAD territory. Ten separate injections will be delivered into the LV free wall (20 X 106 cells / 400 micro lit). The injection sites will be marked with Titanium surgical clips. Subjects will be managed at all times by the current standard of care in this hospital for the patients with an LVAD. Routine postoperative care procedures will be followed with close follow-up for dysrrhythmias or signs of infection.
Tissue sample from the core of the left ventricular apex removed at the time of implantation of LVAD will be compared with the myocardium (marked with the surgical clips) from the explanted heart at the time of transplantation. These samples from the experimental subjects and control hearts will be examined for morphology for interstitial fibrosis, hypertrophy, myocyte diameter and myocytolysis as well as for gene expression using RT-PCR.
Research-related follow-up will take place at weeks 2, 4, 6, 8 and months 6, 12, 18 and 24 after LVAD implant at the Clinical Trial Center of the Cardiology Division at the University of Minnesota. Patients will be examined by the PI or Sub-I at each visit. Follow up data to be obtained at these clinic visits is outlined in the protocol
- Conditions
- Heart Failure
- Being tested
- Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells
- Keywords
- Heart failure, Left ventricular assist device, Stem cells
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intramyocardial Delivery of Bone Marrow Derived Mononuclear CellsBiological
Ten separate injections will be delivered into the LV free wall (20 X 106 cells / 400 micro lit).
| Study group | Role | What they receive |
|---|---|---|
| Stem Cell therapy | Experimental | Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells in Patients with Severe LV Dysfunction and LVAD Support Receives: Biological: Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells |
| Placebo | Placebo comparator | Intramyocardial Delivery Placebo solution into Patients with Severe LV Dysfunction and LVAD Support Receives: Biological: Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Cell Delivery
Safety as measured by the total number of adverse events per group.
Measured: 24 months
Improvement in Myocardial Viability by PET/CT Scan
Change in LAD segments from baseline to 10 weeks. PET scan viability is reported by segment on a scale of 0-4. A score of 0, 1, or 2 are categorized as viable/healthy heart tissue and a score of 3 or 4 are categorized as not viable/scar tissue. No change or better in viability will be reported to determine safety of cell injection. Measurement is reported as number of segment that remained the same or improved were considered "safe" for stem cell injection.
Measured: baseline, 10 weeks
Combined End Points of Death
Number of participants who expired during the study.
Measured: 24 months
Secondary outcomes (3)
Number of Participants Turned Down Without Meeting LVAD Stopping Rules
LVAD turn-down was completed at 10 weeks. Hemodynamic measurements were taken and reported with nominal LVAD support and then again at peak exercise. LVAD turn-down protocol was followed to ensure safety of patient while turning down their LVAD support. After each turn-down we waited 10 minutes and repeated ECHO, RHC, LVAD parameters, vital signs.
Stopping parameters for turn down:
- Significant symptoms (clinician judgement, although low threshold to stop test)
- CVP>20 or increase by more than 10 (e.g., 5 to 16)
- PCWP>25 or increase by more than 10 (e.g., 11 to 22)
- Hypotension
- Increase in LVIDd by >1.5 cm
- Aortic valve opening minimally (less than 1 in 5 beats, e.g.)
The number of patients that could be turn-down without meeting stopping rules and were able to exercise were reported per group.
Measured: 10 weeks
Change in Left Ventricular Dimensions
Change in left ventricular dimensions assessed by ECHO at baseline compared to 10 weeks with LVAD turn-down to 6000 RPMs.
Measured: 10 weeks
Histological Assessment
Data collection was insufficient for data analysis. Samples were collected but no histological analysis performed.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2009 (estimated)
- Study start10 Nov 2011
- Primary completion29 Mar 2016
- Study completion29 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ganesh Raveendran, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00869024
- Sponsor's protocol ID
- 1106M00401
- Acronym
- ASSURANCE
- Status last verified
- Feb 2020
- First submitted
- 24 Mar 2009
- Last updated
- 13 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AsseSsment of Efficacy, Safety and Utility of intRa myocardiAl iNjection of Stem Cells in Patients With End Stage Heart Failure Undergoing LVAD Implantation (ASSURANCE)
- ClinicalTrials.gov ID
- NCT00869024
- Acronym / sponsor ID
- ASSURANCE / 1106M00401
- Conditions
- Heart Failure
- Keywords
- Heart failure, Left ventricular assist device, Stem cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 10 Nov 2011 (actual)
- Primary completion
- 29 Mar 2016 (actual)
- Study completion
- 29 Mar 2016 (actual)
- First posted
- 25 Mar 2009 (estimated)
- Results
- Posted 13 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if the delivery of cells just after implantation of left ventricular assist device will help to improve the pumping function of your heart and minimize heart enlargement in the future.
The cells will be obtained by aspiration or withdrawal of fluid from your bone marrow from your pelvic bone using a needle and syringe. This would not take place until 24-48 hours prior to your planned left ventricular assist device implantation. During the surgery the surgeons will inject the prepared cells that were taken from your bone marrow and inject it into your heart muscle.
This study will test whether receiving your own bone marrow cells directly into your heart will help your heart to recover function after placement of a left ventricular assist device.
Detailed description
Patients who meet the inclusion and exclusion criteria and agree to participate will be enrolled in the study. All the patients will have a baseline EKG, Laboratory tests, 2D ECHO and PET/CT imaging.Day prior to the LVAD implantation all the patients will undergo bone marrow aspiration. Bone marrow aspirate will be processed according to the protocols used by that facility. After processing, the bone marrow mononuclear cells will then be suspended in 2ml of 5% human serum albumin and labeled per the standard protocol of the facility.
Patients will be randomized in a 2:1 fashion either to receive cells or 5% serum albumin. Under general anesthesia using the standard techniques the HeartMate II (LVAD) will be placed. The LVAD will be inserted into the LV apex (with removal of 2 x 2 cm ventricular core). The tissue core will be processed for RNA isolation and morphological analysis. CV surgeon will inject either the cells or placebo directly in to the myocardium in the LAD territory. Ten separate injections will be delivered into the LV free wall (20 X 106 cells / 400 micro lit). The injection sites will be marked with Titanium surgical clips. Subjects will be managed at all times by the current standard of care in this hospital for the patients with an LVAD. Routine postoperative care procedures will be followed with close follow-up for dysrrhythmias or signs of infection.
Tissue sample from the core of the left ventricular apex removed at the time of implantation of LVAD will be compared with the myocardium (marked with the surgical clips) from the explanted heart at the time of transplantation. These samples from the experimental subjects and control hearts will be examined for morphology for interstitial fibrosis, hypertrophy, myocyte diameter and myocytolysis as well as for gene expression using RT-PCR.
Research-related follow-up will take place at weeks 2, 4, 6, 8 and months 6, 12, 18 and 24 after LVAD implant at the Clinical Trial Center of the Cardiology Division at the University of Minnesota. Patients will be examined by the PI or Sub-I at each visit. Follow up data to be obtained at these clinic visits is outlined in the protocol
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stem Cell therapy | Experimental | Biological: Intramyocardial Delivery of Bone Marrow Derived Mononuclear CellsIntramyocardial Delivery of Bone Marrow Derived Mononuclear Cells in Patients with Severe LV Dysfunction and LVAD Support |
| Placebo | Placebo comparator | Biological: Intramyocardial Delivery of Bone Marrow Derived Mononuclear CellsIntramyocardial Delivery Placebo solution into Patients with Severe LV Dysfunction and LVAD Support |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Severe LV dysfunction with EF < 30% with cardiomyopathy ( Ischemic and non ischemic)
- NYHA Class III and IV
- No revascularization options available
- LVAD placement as destination therapy or bridging to transplantation
- Age between 18-80 years
Key exclusion criteria (11 listed)
- History of recent malignancy( less than one year) .
- Unstable hemodynamics at the time of the implant; defined by need for increasing vasopressor medication in the last 24 hours or blood pressure < 70 systolic, or cardiac index < 1.3 liters/min.
- Coronary anatomy suitable for revascularization at the time of surgery
- Pregnancy confirmed by positive urine test
- Lactating mothers
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 |
|---|---|---|
| Intramyocardial Delivery of Bone Marrow Derived Mononuclear CellsTen separate injections will be delivered into the LV free wall (20 X 106 cells / 400 micro lit). | Biological | Placebo, Stem Cell therapy |
Primary outcome
Safety of Cell Delivery
Time frame: 24 months
Safety as measured by the total number of adverse events per group.
Improvement in Myocardial Viability by PET/CT Scan
Time frame: baseline, 10 weeks
Change in LAD segments from baseline to 10 weeks. PET scan viability is reported by segment on a scale of 0-4. A score of 0, 1, or 2 are categorized as viable/healthy heart tissue and a score of 3 or 4 are categorized as not viable/scar tissue. No change or better in viability will be reported to determine safety of cell injection. Measurement is reported as number of segment that remained the same or improved were considered "safe" for stem cell injection.
Combined End Points of Death
Time frame: 24 months
Number of participants who expired during the study.
3 secondary outcomes
Number of Participants Turned Down Without Meeting LVAD Stopping Rules
Time frame: 10 weeks
Change in Left Ventricular Dimensions
Time frame: 10 weeks
Histological Assessment
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
Ganesh Raveendran, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intramyocardial Delivery of Bone Marrow Derived Mononuclear Cells in people with Heart Failure, run by University of Minnesota 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 5 inclusion and 11 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 13 Mar 2020. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety of Cell Delivery (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2020.