Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02065245
Recruitment Status : Active, not recruiting
First Posted : February 17, 2014
Last Update Posted : September 26, 2018
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

Tracking Information
First Submitted Date  ICMJE February 14, 2014
First Posted Date  ICMJE February 17, 2014
Last Update Posted Date September 26, 2018
Actual Study Start Date  ICMJE March 3, 2014
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
Incidence of any treatment emergent-serious adverse events [ Time Frame: One Month post infusion ]
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: 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
Original Primary Outcome Measures  ICMJE
 (submitted: February 14, 2014)
Incidence of any treatment emergent-serious adverse events (TE-SAEs) [ Time Frame: One Month post infusion ]
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
Change History Complete list of historical versions of study NCT02065245 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2017)
  • Difference in rate of decline of Frailty [ Time Frame: At baseline, 3 month and 6 months follow-up visits. ]
    • Difference in rate of decline of Frailty defined as:
    • Reduced Activity (assessed via CHAMPS questionnaire)
    • Slowing of Mobility (assessed via a 4 meter gait speed test and Short Physical Performance Battery (SPPB) assessment)
    • Weight Loss
    • Diminished handgrip strength (assessed via dynamometer)
    • Exhaustion (assessed via the Multi-dimensional fatigue inventory questionnaire) decrease in subject quality of life assessment(s)
  • Difference in subject quality of life assessment(s): [ Time Frame: At baseline, 3 month and 6 months follow-up visits. ]
    • Difference in subject quality of life assessment(s):
  • Death from any cause [ Time Frame: At baseline, 3 month and 6 months follow-up visits. ]
    Death from any cause.
  • Exercise change in ejection fraction. [ Time Frame: At baseline, 3 month and 6 months follow-up visits. ]
    Exercise change in ejection fraction using dobutamine stress echo.
  • Inflammatory Markers. [ Time Frame: At baseline, 3 month and 6 months follow-up visits. ]
    • The following panel of inflammatory markers: C-reactive protein (CRP), Interleukin-6, D-dimer, fibrinogen, complete blood count with differential, DNA, and Tumor necrosis factor-alpha (TNFa)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2014)
  • Difference in rate of decline of Frailty [ Time Frame: At baseline and 6 months. ]
    • 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. ]
    • Difference in subject quality of life assessment(s):
  • Death from any cause [ Time Frame: At baseline and 6 months. ]
    Death from any cause.
  • Exercise change in ejection fraction. [ Time Frame: At baseline and 6 months. ]
    Exercise change in ejection fraction.
  • Inflammatory Markers. [ Time Frame: At Baseline and 6 months. ]
    • The following panel of inflammatory markers: C-reactive protein (CRP), Interleukin-6, D-dimer, fibrinogen, complete blood count with differential, DNA, cytomegalovirus, and TNFα
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery.
Official Title  ICMJE 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.
Brief Summary

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, up to thirty (30) subjects are scheduled to undergo infusion and meeting all inclusion/exclusion criteria will be evaluate at baseline.

An additional twenty (20) subjects will be enrolled in a safety trial for antibiotic free cells.

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.

PILOT STUDY At the pilot subjects one year phone call visit, all fifteen (15) pilot subjects will be provided with the option of having up to four additional infusions of allogeneic hMSCs.

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. Subjects that receive placebo in the randomized phase may be eligible to receive a dose of stem cells (allo--hMSCs).

Approximately fifteen (15) subjects will be enrolled in the pilot phase and thirty (30) subjects will be enrolled in the randomized phase with Frailty will be enrolled. Subjects will then be enrolled and randomized 1:1:1 to an active arm or placebo. If a subject received placebo, in the randomized phase they may be eligible / have the option to receive one infusion of allogeneic hMSCs.

An additional twenty (20) subjects will be enrolled in a safety trial for antibiotic free cells.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Aging Frailty
Intervention  ICMJE
  • Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
    Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
  • Biological: Placebo
    Placebo
Study Arms  ICMJE
  • 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.
    Intervention: Biological: 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.
    Intervention: Biological: 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.
    Intervention: Biological: 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.
    Intervention: Biological: 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.
    Intervention: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
  • Placebo Comparator: Randomized Phase - Group C
    Group C (10 subjects) - Placebo delivered via peripheral intravenous infusion.
    Intervention: Biological: 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.
    Intervention: Biological: 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.
    Intervention: Biological: 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.

    Intervention: Biological: 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.
    Intervention: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 14, 2016)
65
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2014)
45
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 mIU (milli-international units) /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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02065245
Other Study ID Numbers  ICMJE 20130646
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Joshua M Hare, University of Miami
Study Sponsor  ICMJE Joshua M Hare
Collaborators  ICMJE The EMMES Corporation
Investigators  ICMJE
Principal Investigator: Joshua M Hare, MD ISCI / University of Miami Miller School of Medicine
PRS Account University of Miami
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP