Frailty
Conditions
Keywords
Aging Frailty, Frailty, Cardiovascular, Stem Cells
Brief summary
The purpose of this study is to look at the safety of treatment with stem cells in patients with Frailty.
Interventions
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion
BIOLOGICALPlacebo
Placebo administered by peripheral intravenous infusion.
BIOLOGICALPenicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion.
Sponsors
The Emmes Company, LLC
Longeveron Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Provide written informed consent. * Subjects age greater than or equal to 60 and less than or equal to 95 years at the time of signing the Informed Consent Form. * Show signs of frailty apart from a concomitant condition as assessed by the Investigator with a frailty score of 4 to 7 using the Clinical Frailty Scale * Female subjects with an Follicle-stimulating hormone (FSH) equal to or \> 25.8 milli-international units (mIU) /mL (milliliter), if not currently on hormone replacement therapy.
Exclusion criteria
* Score of less than or equal to 24 on the Mini Mental State Examination (MMSE) * Inability to perform any of the assessments required for endpoint analysis (report safety or tolerability concerns, perform pulmonary function tests, undergo blood draws, read and respond to questionnaires. * Active listing (or expected future listing) for transplant of any organ. * Clinically important abnormal screening laboratory values, including but not limited to: hemoglobin \<8 g/dl, white blood cell count \<3000/mm3, platelets\<80,000/mm3, international normalized ratio (INR) \> 1.5 not due to a reversible cause (i.e. Coumadin), aspartate transaminase, alanine transaminase, or alkaline phosphatase \> 3 times upper limit of normal, total bilirubin \> 1.5 mg/dl. * Serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. Including, but not limited to: HIV, advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, or cardiac revascularization within the last six months, or severe obstructive ventilatory defect. * Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. * Be an organ transplant recipient. * Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma if recurrence occurs. * Have a non-pulmonary condition that limits lifespan to \< 1 year. * Have a history of drug or alcohol abuse within the past 24 months. * Be serum positive for HIV, hepatitis B Surface Antigen (BsAg) or Viremic hepatitis C. * Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial. * Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion. * Have hypersensitivity to dimethyl sulfoxide (DMSO)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | One Month post infusion | Incidence of any treatment-emergent serious adverse events (SAE), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities. * Serum chemistry: chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (fractionate if total \>1.5 times normal), alkaline phosphatase, albumin, * Hematology (Complete blood count): hemoglobin, hematocrit, platelets, white blood cells (WBC), WBC differential |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Slowing of Mobility as Measured by 4 Meter Gait Speed Test | At baseline and 6 month follow-up visit. | 4-meter gait speed test measures the time (in seconds) taken to walk a distance of 4 meters. The total score has a range of 1 point - 4 points with the higher score indicating faster walk speed. |
| Change in Slowing of Mobility as Measured by SPPB | At baseline and 6 month follow-up visit. | Standard Physical Performance Battery (SPPB) Assessment has total score ranging from 0-4 with the higher score indicating better balance. |
| Change in Weight | At baseline and 6 month follow-up visit. | Change in weight as measured in kilograms (kg). |
| Change in Diminished Hand Grip Strength | At baseline and 6 month follow-up visit. | Hand grip strength as assessed by a dynamometer. Grip strength is recorded (in mmHg) three times for each hand. The average reading is reported for each hand. |
| Change in Exhaustion as Measured by the MFI Questionnaire | At baseline and 6 month follow-up visit. | Multi-dimensional Fatigue Inventory (MFI) Questionnaire contains 20 questions with a 5-point scale. The MFI has total score ranging from 20-100 with the higher score indicating less fatigue. |
| Change in Quality of Life (QoL) as Measured by the ICECAP Questionnaire | At baseline and 6 month follow-up visit. | Investigating Choice Experiences for the Preferences of Older People (ICEpop) Capability measure for Older people (ICECAP) questionnaire has total score ranging from 5-20 with the higher score indicating greater quality of life. |
| Change in Quality of Life (QoL) as Measured by the SF-36 Questionnaire | At baseline and 6 month follow-up visit. | Short Form (SF)-36 Questionnaire has 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. Lower scores indicate the more disability, and higher scores indicate less disability. |
| Change in Frailty as Assessed by CHAMPS Questionnaire | At baseline and 6 month follow-up visit. | Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire measures duration of exercise-related activities (hours/week). The Duration variable can range from 0 - 399.75 hours per week. Higher scores indicate more activity. |
| Change in Quality of Life (QoL) as Measured by the EQ-5D-3L Overall Health Status Scale. | At baseline and 6 month follow-up visit. | EuroQoL - 5 Dimension - 3 levels (EQ-5D-3L) Overall health status question has a range of 0-100. Higher scores indicate better Quality of Life. |
| Change in Sense of Smell as Measured by UPSIT | At baseline and 6 month follow-up visit. | University of Pennsylvania Smell Identification Test (UPSIT) smell test booklet has a total score ranging from 0-40 with higher scores indicating better olfaction. |
| Death | Up to 12 months. | Any reported death from any cause. |
| Change in Ejection Fraction (EF) | At baseline and 6 month follow-up visit. | Change in dobutamine stress echocardiogram induced ejection fraction |
| Change in Inflammatory Markers Levels | At baseline and 6 month follow-up visit. | Change in inflammatory markers including C-Reactive Protein (CRP) and Fibrinogen serum samples as measured in mg/L. |
| Change in Inflammatory Markers | At baseline and 6 month follow-up visit. | Change in inflammatory markers including Interleukin (IL)-6 and Tumor Necrosis Factor (TNF) Alpha from serum samples as measured in pg/mL. |
| Change in Inflammatory Marker D-dimer Levels | At baseline and 6 month follow-up visit. | Change in inflammatory marker D-Dimer from serum samples as measured in mg/dL. |
| Change in Quality of Life (QoL) as Measured by the EQ-5D-3L Questionnaire | At baseline and 6 month follow-up visit. | EuroQoL (EQ)- 5 Dimension (5D)- 3 levels (3L) Questionnaire has total score ranging from 0-10 for the 5 dimensions. Higher scores indicate better Quality of Life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pilot Phase - Group 1 Group 1 participants will receive Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 20 million allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion | 5 |
| Pilot Phase - Group 2 Group 2 - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion | 5 |
| Pilot Phase - Group 3 Group 3 - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion | 5 |
| Randomized Phase - Group A Group A - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million allo-hMSCs/kg delivered via peripheral intravenous infusion.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion | 10 |
| Randomized Phase - Group B Group B - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million allo-hMSCs/kg delivered via peripheral intravenous infusion.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion | 10 |
| Randomized Phase - Group C Group C - Placebo delivered via peripheral intravenous infusion. Participants in this group have the option to receive one additional infusion of 100million allo-hMSCs/kg with a 12 to 18 month interval.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion
Placebo: Placebo administered by peripheral intravenous infusion. | 10 |
| Addendum B - Antibiotic Free Cell Group Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million penicillin/streptomycin-free allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion
Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion. | 20 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Infusion 1 | Death | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Infusion 1 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Infusion 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Infusion 3 | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Randomized Phase - Group B | Total | Pilot Phase - Group 1 | Addendum B - Antibiotic Free Cell Group | Randomized Phase - Group C | Pilot Phase - Group 2 | Pilot Phase - Group 3 | Randomized Phase - Group A |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 75.9 years STANDARD_DEVIATION 8.293 | 75.015 years STANDARD_DEVIATION 7.443 | 78.8 years STANDARD_DEVIATION 5.167 | 72.75 years STANDARD_DEVIATION 8.896 | 74.7 years STANDARD_DEVIATION 6.75 | 75.8 years STANDARD_DEVIATION 4.868 | 79.2 years STANDARD_DEVIATION 4.024 | 74.6 years STANDARD_DEVIATION 7.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 60 Participants | 5 Participants | 19 Participants | 8 Participants | 5 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 64 Participants | 5 Participants | 20 Participants | 10 Participants | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 4 Participants | 24 Participants | 3 Participants | 7 Participants | 4 Participants | 0 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 41 Participants | 2 Participants | 13 Participants | 6 Participants | 5 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 1 / 5 | 0 / 10 | 1 / 10 | 0 / 10 | 1 / 20 |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 20 |
| serious Total, serious adverse events | 0 / 5 | 1 / 5 | 1 / 5 | 0 / 10 | 2 / 10 | 0 / 10 | 1 / 20 |
Outcome results
Primary
Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs)
Incidence of any treatment-emergent serious adverse events (SAE), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities. * Serum chemistry: chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (fractionate if total \>1.5 times normal), alkaline phosphatase, albumin, * Hematology (Complete blood count): hemoglobin, hematocrit, platelets, white blood cells (WBC), WBC differential
Time frame: One Month post infusion
Population: Participants were allowed to opt-in to receive additional infusion based on cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pilot Phase - Group 1 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 0 Incidents |
| Pilot Phase - Group 1 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | infusion #4 | 0 Incidents |
| Pilot Phase - Group 1 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #3 | 0 Incidents |
| Pilot Phase - Group 1 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #2 | 0 Incidents |
| Pilot Phase - Group 2 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 0 Incidents |
| Pilot Phase - Group 2 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #2 | 0 Incidents |
| Pilot Phase - Group 2 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #3 | 0 Incidents |
| Pilot Phase - Group 2 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | infusion #4 | 1 Incidents |
| Pilot Phase - Group 3 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 0 Incidents |
| Pilot Phase - Group 3 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #3 | 0 Incidents |
| Pilot Phase - Group 3 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | infusion #4 | 0 Incidents |
| Pilot Phase - Group 3 | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #2 | 0 Incidents |
| Randomized Phase - Group A | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 0 Incidents |
| Randomized Phase - Group B | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 1 Incidents |
| Randomized Phase - Group C | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 0 Incidents |
| Randomized Phase - Group C | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #2 | 0 Incidents |
| Addendum B - Antibiotic Free Cell Group | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #1 | 0 Incidents |
| Addendum B - Antibiotic Free Cell Group | Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) | Infusion #2 | 0 Incidents |
Secondary
Change in Diminished Hand Grip Strength
Hand grip strength as assessed by a dynamometer. Grip strength is recorded (in mmHg) three times for each hand. The average reading is reported for each hand.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Ejection Fraction (EF)
Change in dobutamine stress echocardiogram induced ejection fraction
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Exhaustion as Measured by the MFI Questionnaire
Multi-dimensional Fatigue Inventory (MFI) Questionnaire contains 20 questions with a 5-point scale. The MFI has total score ranging from 20-100 with the higher score indicating less fatigue.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Frailty as Assessed by CHAMPS Questionnaire
Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire measures duration of exercise-related activities (hours/week). The Duration variable can range from 0 - 399.75 hours per week. Higher scores indicate more activity.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Inflammatory Marker D-dimer Levels
Change in inflammatory marker D-Dimer from serum samples as measured in mg/dL.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Inflammatory Markers
Change in inflammatory markers including Interleukin (IL)-6 and Tumor Necrosis Factor (TNF) Alpha from serum samples as measured in pg/mL.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Inflammatory Markers Levels
Change in inflammatory markers including C-Reactive Protein (CRP) and Fibrinogen serum samples as measured in mg/L.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Quality of Life (QoL) as Measured by the EQ-5D-3L Overall Health Status Scale.
EuroQoL - 5 Dimension - 3 levels (EQ-5D-3L) Overall health status question has a range of 0-100. Higher scores indicate better Quality of Life.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Quality of Life (QoL) as Measured by the EQ-5D-3L Questionnaire
EuroQoL (EQ)- 5 Dimension (5D)- 3 levels (3L) Questionnaire has total score ranging from 0-10 for the 5 dimensions. Higher scores indicate better Quality of Life.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Quality of Life (QoL) as Measured by the ICECAP Questionnaire
Investigating Choice Experiences for the Preferences of Older People (ICEpop) Capability measure for Older people (ICECAP) questionnaire has total score ranging from 5-20 with the higher score indicating greater quality of life.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Quality of Life (QoL) as Measured by the SF-36 Questionnaire
Short Form (SF)-36 Questionnaire has 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. Lower scores indicate the more disability, and higher scores indicate less disability.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Sense of Smell as Measured by UPSIT
University of Pennsylvania Smell Identification Test (UPSIT) smell test booklet has a total score ranging from 0-40 with higher scores indicating better olfaction.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Slowing of Mobility as Measured by 4 Meter Gait Speed Test
4-meter gait speed test measures the time (in seconds) taken to walk a distance of 4 meters. The total score has a range of 1 point - 4 points with the higher score indicating faster walk speed.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Slowing of Mobility as Measured by SPPB
Standard Physical Performance Battery (SPPB) Assessment has total score ranging from 0-4 with the higher score indicating better balance.
Time frame: At baseline and 6 month follow-up visit.
Secondary
Change in Weight
Change in weight as measured in kilograms (kg).
Time frame: At baseline and 6 month follow-up visit.
Secondary
Death
Any reported death from any cause.
Time frame: Up to 12 months.