AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery

Study Overview
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Brief Summary
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The purpose of this study is to look at the safety of treatment with stem cells in patients with Frailty.

Official Title
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A Phase I/II, Randomized, Blinded and Placebo-controlled Trial to Evaluate the Safety and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion in Patients With Aging Frailty

Conditions
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Frailty

Intervention / Treatment
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* Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
* Biological: Placebo
* Biological: Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pilot phase - Group 1<br>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. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>|
| Experimental: Pilot Phase - Group 2<br>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. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>|
| Experimental: Pilot Phase - Group 3<br>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. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>|
| Experimental: Randomized Phase - Group A<br>Group A - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million allo-hMSCs/kg delivered via peripheral intravenous infusion. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>|
| Experimental: Randomized phase - Group B<br>Group B - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million allo-hMSCs/kg delivered via peripheral intravenous infusion. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>|
| Experimental: Randomized Phase - Group C<br>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. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>Biological: Placebo<br>* Placebo administered by peripheral intravenous infusion.<br>|
| Experimental: Addendum B - Antibiotic free cell Group<br>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. | Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion<br>Biological: Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)<br>* Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | One Month post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| Change in Weight | Change in weight as measured in kilograms (kg). | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| Death | Any reported death from any cause. | Up to 12 months. | 
| Change in Ejection Fraction (EF) | Change in dobutamine stress echocardiogram induced ejection fraction | At baseline and 6 month follow-up visit. | 
| Change in Inflammatory Markers Levels | Change in inflammatory markers including C-Reactive Protein (CRP) and Fibrinogen serum samples as measured in mg/L. | At baseline and 6 month follow-up visit. | 
| 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. | At baseline and 6 month follow-up visit. | 
| Change in Inflammatory Marker D-dimer Levels | Change in inflammatory marker D-Dimer from serum samples as measured in mg/dL. | At baseline and 6 month follow-up visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging Frailty, Frailty, Cardiovascular, Stem Cells