NCT02065245

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
65

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2014

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 14, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 17, 2014

Completed
14 days until next milestone

Study Start

First participant enrolled

March 3, 2014

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 2, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 2, 2020

Completed
7 months until next milestone

Results Posted

Study results publicly available

April 27, 2021

Completed
Last Updated

July 14, 2021

Status Verified

July 1, 2021

Enrollment Period

5.6 years

First QC Date

February 14, 2014

Results QC Date

March 30, 2021

Last Update Submit

July 13, 2021

Conditions

Frailty

Keywords

Aging FrailtyFrailtyCardiovascularStem Cells

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (16)

  • Change in Frailty as Assessed by CHAMPS Questionnaire

    At baseline and 6 month follow-up visit.

  • Change in Slowing of Mobility as Measured by 4 Meter Gait Speed Test

    At baseline and 6 month follow-up visit.

  • Change in Slowing of Mobility as Measured by SPPB

    At baseline and 6 month follow-up visit.

  • Change in Weight

    At baseline and 6 month follow-up visit.

  • Change in Diminished Hand Grip Strength

    At baseline and 6 month follow-up visit.

  • +11 more secondary outcomes

Study Arms (7)

Pilot phase - Group 1

EXPERIMENTAL

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)

Pilot Phase - Group 2

EXPERIMENTAL

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)

Pilot Phase - Group 3

EXPERIMENTAL

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)

Randomized Phase - Group A

EXPERIMENTAL

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)

Randomized phase - Group B

EXPERIMENTAL

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)

Randomized Phase - Group C

EXPERIMENTAL

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)Biological: Placebo

Addendum B - Antibiotic free cell Group

EXPERIMENTAL

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

Interventions

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Addendum B - Antibiotic free cell GroupPilot Phase - Group 2Pilot Phase - Group 3Pilot phase - Group 1Randomized Phase - Group ARandomized Phase - Group CRandomized phase - Group B
PlaceboBIOLOGICAL

Placebo administered by peripheral intravenous infusion.

Randomized Phase - Group C
Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)BIOLOGICAL

Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion.

Addendum B - Antibiotic free cell Group

Eligibility Criteria

Age60 Years - 95 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

ISCI/University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (3)

  • Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, Schulman IH, Longsomboon B, Wolf A, Khan A, Heldman AW, Goldschmidt-Clermont PJ, Hare JM. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: 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. Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.

    PMID: 26933813BACKGROUND

  • Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137.

    PMID: 28977399BACKGROUND

  • Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, Heldman AW, Miki R, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Pujol MV, Da Fonseca M, Oliva AA Jr, Green G, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Goldschmidt-Clermont PJ, Hare JM. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1505-1512. doi: 10.1093/gerona/glx056.

    PMID: 28444181BACKGROUND

Related Links

MeSH Terms

Conditions

Frailty

Interventions

Penicillins

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

beta-LactamsLactamsAmidesOrganic ChemicalsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Joshua M Hare, MD
Organization
University of Miami, Miller School of Medicine - Interdisciplinary Stem Cell Institute (ISCI)
JHare@med.miami.edu
305-243-5579

Study Officials

  • Joshua M Hare, MD

    ISCI / University of Miami Miller School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 14, 2014

First Posted

February 17, 2014

Study Start

March 3, 2014

Primary Completion

October 2, 2019

Study Completion

October 2, 2020

Last Updated

July 14, 2021

Results First Posted

April 27, 2021

Record last verified: 2021-07

Data Sharing

IPD Sharing
Will not share

Locations

US(1)