Coronary Microvascular Dysfunction
Conditions
Brief summary
This clinical trial will explore the safety and effect of GCSF-mobilized autologous ex vivo selected CD34 cells for the treatment of CMD in adults currently experiencing angina and with no obstructive coronary artery disease. Eligible subjects will receive a single intracoronary infusion of CLBS16.
Interventions
BIOLOGICALCLBS16
GCSF-mobilized autologous CD34 cells
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Cedars-Sinai Medical Center
Mayo Clinic
Lisata Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women age ≥18 * History of and currently experiencing angina at least 3 times per week * No obstructive coronary artery disease * On stable medical therapy for 30 days prior to enrollment * Must agree to use a reliable and acceptable method of contraception for the duration of participation * Written informed consent
Exclusion criteria
* Myocardial infarction within 90 days * Prior evidence of obstructive heart disease including PCI or CABG (or planned PCI or CABG) * Diagnosis of other specific cardiac disease * Must meet LVEF and GFR requirements * Current use of coumadin or DOACs * Hypersensitivity to G-CSF, apheresis or study product components * Positive for HIV, hepatitis B or hepatitis C * Active inflammatory or autoimmune disease, or chronic immunosuppressive state * Drug abuse * Pregnant or lactating * Malignant neoplasm within 5 years * History of Sickle Cell Disease * Participation in another clinical study within 90 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Coronary Flow Reserve | Day 180 | Coronary Flow Reserve (CFR) is a measure of coronary microvascular function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peripheral Arterial Tonometry | Day 180 | — |
| Change in Angina Frequency From Baseline | 6 months | — |
| Change From Baseline in Microvascular Function as Assessed by Intracoronary Administration of Acetylcholine | Day 180 | — |
| Change From Baseline in Seattle Angina Questionnaire | 6 months | The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life). |
| Change From Baseline in SF-36 Scores | 6 months | The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. |
| Canadian Cardiovascular Society Angina Class | 6 months | Canadian Cardiovascular Society angina class grading scale is assessed according to the following scores: Grade 1: Ordinary physical activity does not cause angina, such as walking and climbing stairs. Angina with strenuous or rapid or prolonged exertion at work or recreation Grade 2: Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold, or in wind, or under emotional stress, or only during the few hours after awakening. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions Grade 3: Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in normal conditions and at normal pace Grade 4: Inability to carry on any physical activity without discomfort, anginal syndrome may be present at rest A higher grade is a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous CD34 Cells Open label active treatment arm. Subjects receive autologous CD34 cells.
CLBS16: GCSF-mobilized autologous CD34 cells | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Autologous CD34 Cells |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 54.3 years STANDARD_DEVIATION 12.72 |
| Body Mass Index | 29.52 kg/m^2 STANDARD_DEVIATION 7.322 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 3 Participants |
| Weight | 83.36 kg STANDARD_DEVIATION 23.377 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 6 / 20 |
Outcome results
Primary
Change From Baseline in Coronary Flow Reserve
Coronary Flow Reserve (CFR) is a measure of coronary microvascular function.
Time frame: Day 180
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous CD34 Cells | Change From Baseline in Coronary Flow Reserve | 0.62 ratio | Standard Deviation 0.835 |
Secondary
Canadian Cardiovascular Society Angina Class
Canadian Cardiovascular Society angina class grading scale is assessed according to the following scores: Grade 1: Ordinary physical activity does not cause angina, such as walking and climbing stairs. Angina with strenuous or rapid or prolonged exertion at work or recreation Grade 2: Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold, or in wind, or under emotional stress, or only during the few hours after awakening. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions Grade 3: Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in normal conditions and at normal pace Grade 4: Inability to carry on any physical activity without discomfort, anginal syndrome may be present at rest A higher grade is a worse outcome.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous CD34 Cells | Canadian Cardiovascular Society Angina Class | -1.21 change in grade | Standard Deviation 1.032 |
Secondary
Change From Baseline in Microvascular Function as Assessed by Intracoronary Administration of Acetylcholine
Time frame: Day 180
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous CD34 Cells | Change From Baseline in Microvascular Function as Assessed by Intracoronary Administration of Acetylcholine | 9.4 % change in peak coronary blood flow | Standard Deviation 105.408 |
Secondary
Change From Baseline in Peripheral Arterial Tonometry
Time frame: Day 180
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous CD34 Cells | Change From Baseline in Peripheral Arterial Tonometry | -0.19 Reactive Hyperemia Index (ratio) | Standard Deviation 0.99 |
Secondary
Change From Baseline in Seattle Angina Questionnaire
The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life).
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous CD34 Cells | Change From Baseline in Seattle Angina Questionnaire | Physical limitation scale | 16.81 change in scale score | Standard Deviation 20.956 |
| Autologous CD34 Cells | Change From Baseline in Seattle Angina Questionnaire | Angina stability scale | 23.61 change in scale score | Standard Deviation 40.649 |
| Autologous CD34 Cells | Change From Baseline in Seattle Angina Questionnaire | Angina frequency scale | 18.33 change in scale score | Standard Deviation 28.952 |
| Autologous CD34 Cells | Change From Baseline in Seattle Angina Questionnaire | Treatment satisfaction scale | 12.83 change in scale score | Standard Deviation 19.925 |
| Autologous CD34 Cells | Change From Baseline in Seattle Angina Questionnaire | Disease perception scale | 23.68 change in scale score | Standard Deviation 24.417 |
Secondary
Change From Baseline in SF-36 Scores
The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Physical component scores | 6.66 change in scale score | Standard Deviation 7.452 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Mental component scores | 5.62 change in scale score | Standard Deviation 8.628 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Physical function | 5.94 change in scale score | Standard Deviation 6.439 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Role-physical | 9.81 change in scale score | Standard Deviation 10.376 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Bodily pain | 5.50 change in scale score | Standard Deviation 6.681 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | General health | 3.53 change in scale score | Standard Deviation 6.666 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Vitality | 8.29 change in scale score | Standard Deviation 8.666 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Social functions | 7.91 change in scale score | Standard Deviation 8.573 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Role-emotional | 6.23 change in scale score | Standard Deviation 11.287 |
| Autologous CD34 Cells | Change From Baseline in SF-36 Scores | Mental health | 4.13 change in scale score | Standard Deviation 7.766 |
Secondary
Change in Angina Frequency From Baseline
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Autologous CD34 Cells | Change in Angina Frequency From Baseline | -2.34 angina episodes per day | Standard Deviation 2.938 |