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FrailtyPhase 1/2CRATUSNCT02065245

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

A Phase 1/2 study testing Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) and Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) in people with Frailty, run by Longeveron Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 60 to 95 years
Conditions the study is for
Frailty
What is being tested?
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) and Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
65 participants
Where
1 siteUnited States
Study dates
3 Mar 2014to 2 Oct 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 95 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • ISCI/University of Miami Miller School of Medicine

    Miami, Florida, 33136

Other trials in United States

About this study

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

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

Conditions
Frailty
Being tested
Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs), Placebo, Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Keywords
Aging Frailty, Frailty, Cardiovascular, Stem Cells
Medical subject headings
Frailty

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

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

  • PlaceboBiological

    Placebo administered by peripheral intravenous infusion.

  • 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.

Study groups in NCT02065245
Study groupRoleWhat they receive
Pilot phase - Group 1ExperimentalGroup 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.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Pilot Phase - Group 2ExperimentalGroup 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.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Pilot Phase - Group 3ExperimentalGroup 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.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Randomized Phase - Group AExperimentalGroup A - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million allo-hMSCs/kg delivered via peripheral intravenous infusion.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Randomized phase - Group BExperimentalGroup B - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million allo-hMSCs/kg delivered via peripheral intravenous infusion.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)
Randomized Phase - Group CExperimentalGroup 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.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs); Biological: Placebo
Addendum B - Antibiotic free cell GroupExperimentalAllogeneic 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.
Receives: Biological: Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs); Biological: Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: One Month post infusion

Secondary outcomes (16)

  1. 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.

    Measured: At baseline and 6 month follow-up visit.

  2. 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.

    Measured: At baseline and 6 month follow-up visit.

  3. 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.

    Measured: At baseline and 6 month follow-up visit.

  4. Change in Weight

    Change in weight as measured in kilograms (kg).

    Measured: At baseline and 6 month follow-up visit.

  5. 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.

    Measured: At baseline and 6 month follow-up visit.

  6. 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.

    Measured: At baseline and 6 month follow-up visit.

  7. 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.

    Measured: At baseline and 6 month follow-up visit.

  8. 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.

    Measured: At baseline and 6 month follow-up visit.

  9. 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.

    Measured: At baseline and 6 month follow-up visit.

  10. 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.

    Measured: At baseline and 6 month follow-up visit.

  11. 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.

    Measured: At baseline and 6 month follow-up visit.

  12. Death

    Any reported death from any cause.

    Measured: Up to 12 months.

  13. Change in Ejection Fraction (EF)

    Change in dobutamine stress echocardiogram induced ejection fraction

    Measured: At baseline and 6 month follow-up visit.

  14. Change in Inflammatory Markers Levels

    Change in inflammatory markers including C-Reactive Protein (CRP) and Fibrinogen serum samples as measured in mg/L.

    Measured: At baseline and 6 month follow-up visit.

  15. 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.

    Measured: At baseline and 6 month follow-up visit.

  16. Change in Inflammatory Marker D-dimer Levels

    Change in inflammatory marker D-Dimer from serum samples as measured in mg/dL.

    Measured: At baseline and 6 month follow-up visit.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2014 (estimated)
  2. Study start3 Mar 2014
  3. Primary completion2 Oct 2019
  4. Study completion2 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02065245
Sponsor's protocol ID
20130646
Acronym
CRATUS
Status last verified
Jul 2021
First submitted
14 Feb 2014
Last updated
14 Jul 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26933813

  • 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.

    PubMed 28977399

  • 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.

    PubMed 28444181

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) and Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) in people with Frailty, run by Longeveron Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs) (time frame: One Month post infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02065245, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2021.

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