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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Miami
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
Joshua M Hare, University of Miami
ClinicalTrials.gov Identifier:
NCT02065245
First received: February 14, 2014
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

Before initiating the full randomized study, a Pilot Safety Phase will be performed. The randomized portion of this trial will be conducted after a full review of the safety data from the Pilot Phase by the Data safety monitoring board.

Following the Pilot Phase of fifteen (15) subjects, thirty (30) subjects are scheduled to undergo infusion and meeting all inclusion/exclusion criteria will be evaluate at baseline.


Condition Intervention Phase
Aging Frailty
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Incidence of any treatment emergent serious adverse events (TE-SAEs) [ Time Frame: One Month post infusion ] [ Designated as safety issue: Yes ]

    Incidence (at one month post infusion) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.

    • Serum chemistry: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, phosphate, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (fractionate if total >1.5 times normal), alkaline phosphatase, γ-glutamyl transaminase (GGT), albumin,
    • Hematology (Complete blood count): hemoglobin, hematocrit, platelets, white blood cells (WBC), WBC differential


Secondary Outcome Measures:
  • Difference in rate of decline of Frailty [ Time Frame: At baseline and 6 months. ] [ Designated as safety issue: No ]

    • Difference in rate of decline of Frailty defined as:

    • Reduced Activity
    • Slowing of Mobility
    • Weight Loss
    • Diminished handgrip strength
    • Exhaustion

  • Difference in subject quality of life assessment(s): [ Time Frame: At baseline and 6 months. ] [ Designated as safety issue: No ]
    • Difference in subject quality of life assessment(s):

  • Death from any cause [ Time Frame: At baseline and 6 months. ] [ Designated as safety issue: No ]
    Death from any cause.

  • Exercise change in ejection fraction. [ Time Frame: At baseline and 6 months. ] [ Designated as safety issue: No ]
    Exercise change in ejection fraction.

  • Inflammatory Markers. [ Time Frame: At Baseline and 6 months. ] [ Designated as safety issue: No ]
    • The following panel of inflammatory markers: C-reactive protein (CRP), Interleukin-6, D-dimer, fibrinogen, complete blood count with differential, DNA, cytomegalovirus, and TNFα


Estimated Enrollment: 45
Study Start Date: February 2014
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Group A (10 subjects) - Allogeneic human mesenchymal stem cells: 100 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Experimental: Group B
Group B (10 subjects) - Allogeneic human mesenchymal stem cells: 200 million cells/ml delivered via peripheral intravenous infusion.
Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Experimental: Group C
Group C (10 subjects) - Placebo delivered via peripheral intravenous infusion.
Biological: Placebo

Detailed Description:

A Pilot Phase will be performed to test the safety of dose and volume escalation of cells administered via peripheral intravenous infusion. The randomized portion of the study will be conducted after a full review of the safety data from the Pilot Phase by the data safety monitoring board.

RANDOMIZATION STUDY

This Phase I/II, randomized, blinded, placebo-controlled study is designed to evaluate the safety and tolerability of allogenic human mesenchymal stem cells in patients with Frailty and to explore potential efficacy over 4 weeks.

Approximately fifteen (15) subjects will be enrolled in the pilot phase and thirty (30) subjects with Frailty will be enrolled for a total of forty-five (45) subjects. Subjects will then be enrolled and randomized 1:1:1 to an active arm or placebo. Additional subjects may be enrolled if deemed appropriate.

Eligible subjects must have a diagnosis or symptoms of frailty as defined by the Canadian Study on Health & Aging. Following informed consent before or at the screening visit, the diagnosis of FRAILTY will be confirmed by investigator review of medical history.

  Eligibility

Ages Eligible for Study:   60 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent.
  • Subjects age greater than or equal to 60 and less than or qual 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

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.
  • Have known allergies to penicillin or streptomycin. 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 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 injection.
  • Female subjects must have an Follicle-stimulating hormone (FSH) < 25.8 IU/L
  • Have hypersensitivity to dimethyl sulfoxide (DMSO)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02065245

Contacts
Contact: Joshua M Hare, MD 305-243-5579 jhare@med.miami.edu

Locations
United States, Florida
ISCI/University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Joshua M Hare, MD    305-243-5579    jhare@med.miami.edu   
Contact: Darcy L DiFede, RN, BSN    305-243-9106    ddifede@med.miami.edu   
Principal Investigator: Joshua M Hare, MD         
Sub-Investigator: Pascal Goldschmidt, MD         
Sponsors and Collaborators
University of Miami
The EMMES Corporation
Investigators
Principal Investigator: Joshua M Hare, MD ISCI / University of Miami Miller School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Joshua M Hare, Chief Science Officer / ISCI Director / Senior Associate Dean, University of Miami
ClinicalTrials.gov Identifier: NCT02065245     History of Changes
Other Study ID Numbers: 20130646
Study First Received: February 14, 2014
Last Updated: August 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Aging Frailty, Frailty, Cardiovascular

ClinicalTrials.gov processed this record on September 22, 2014