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

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ClinicalTrials.gov Identifier: NCT02065245
Recruitment Status : Completed
First Posted : February 17, 2014
Last Update Posted : March 5, 2021
Sponsor:
Collaborator:
The Emmes Company, LLC
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

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

Condition or disease Intervention/treatment Phase
Frailty Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) Biological: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 3, 2014
Actual Primary Completion Date : October 2, 2019
Actual Study Completion Date : October 2, 2020

Arm Intervention/treatment
Experimental: Pilot phase - Group 1
Group 1 (5 subjects) - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 20 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Pilot Phase - Group 2
Group 2 (5 subjects) - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Pilot Phase - Group 3
Group 3 (5 subjects) - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Randomized Phase - Group A
Group A (10 subjects) - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Randomized phase - Group B
Group B (10 subjects) - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Placebo Comparator: Randomized Phase - Group C
Group C (10 subjects) - Placebo delivered via peripheral intravenous infusion.
Biological: Placebo
Placebo

Experimental: Addendum A - Pilot Phase 2nd Infusion
The pilot phase subjects will be able to receive one additional Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Addendum B - Antibiotic free cell Group
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Addendum C - Optional Follow-on Phase

up to 2 additional doses for those that participated in Addendum A and up to 3 additional doses for subjects that took part in Addendum B.

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million cells/ml delivered via peripheral intravenous infusion.

Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Experimental: Addendum D - Optional for Randomized Placebo
Randomized phase subjects that received Placebo will be able to receive one additional Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)




Primary Outcome Measures :
  1. Incidence of any Treatment Emergent - Serious Adverse Events (TE-SAEs) [ Time Frame: 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 Outcome Measures :
  1. Change in Frailty as assessed by CHAMPS Questionnaire [ Time Frame: 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.

  2. Change in slowing of mobility as measured by 4 meter gait speed test [ Time Frame: 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.

  3. Change in slowing of mobility as measured by SPPB [ Time Frame: 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.

  4. Change in weight [ Time Frame: At baseline and 6 month follow-up visit. ]
    Change in weight as measured in kilograms (kg).

  5. Change in diminished hand grip strength [ Time Frame: 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.

  6. Change in exhaustion as measured by the MFI Questionnaire [ Time Frame: 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.

  7. Change in Quality of Life (QoL) as measured by the ICECAP questionnaire [ Time Frame: 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.

  8. Change in Quality of Life (QoL) as measured by the SF-36 questionnaire [ Time Frame: 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.

  9. Change in Quality of Life (QoL) as measured by the EQ-5D-3L questionnaire [ Time Frame: 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.

  10. Change in Quality of Life (QoL) as measured by the EQ-5D-3L overall health status scale. [ Time Frame: 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.

  11. Change in sense of smell as measured by UPSIT [ Time Frame: 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.

  12. Death [ Time Frame: Up to 12 months. ]
    Any reported death from any cause.

  13. Change in Ejection Fraction (EF) [ Time Frame: At baseline and 6 month follow-up visit. ]
    Change in dobutamine stress echocardiogram induced ejection fraction

  14. Change in Inflammatory Markers Levels [ Time Frame: 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.

  15. Change in Inflammatory Markers [ Time Frame: 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.

  16. Change in Inflammatory Marker D-dimer levels [ Time Frame: At baseline and 6 month follow-up visit. ]
    Change in inflammatory marker D-Dimer from serum samples as measured in mg/dL.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02065245


Locations
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United States, Florida
ISCI/University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
Sponsors and Collaborators
Joshua M Hare
The Emmes Company, LLC
Investigators
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Principal Investigator: Joshua M Hare, MD ISCI / University of Miami Miller School of Medicine
Additional Information:
Publications:

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Responsible Party: Joshua M Hare, Chief Science Officer / ISCI Director / Senior Associate Dean, University of Miami
ClinicalTrials.gov Identifier: NCT02065245    
Other Study ID Numbers: 20130646
First Posted: February 17, 2014    Key Record Dates
Last Update Posted: March 5, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joshua M Hare, University of Miami:
Aging Frailty
Frailty
Cardiovascular
Stem Cells
Additional relevant MeSH terms:
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Frailty
Pathologic Processes