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CompletedNCT01775774STARTUpdated Aug 14, 2017Results posted

Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome

A Phase 1 interventional study of Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome, sponsored by Michael A. Matthay. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-08-14.

Sponsored by Michael A. Matthay · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
9
Allocation
Not applicable
Ages
18 Years and older
Sex
All
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Study summary

This is a Phase 1, open label, dose escalation, multi-center clinical trial of Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells (hMSCs) for the treatment of Acute Respiratory Distress Syndrome (ARDS). The purpose of this study is to assess the safety of hMSCs in patients with ARDS.

Read the detailed description

The primary objective of this study is to assess the safety of intravenous infusion of Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells (hMSCs) in patients with ARDS.

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Conditions studied

  • Acute Respiratory Distress Syndrome

Keywords

  • Acute Respiratory Distress Syndrome
  • Acute Lung Injury
  • Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
03

In context

Respiratory Distress Syndrome

1,597 studies on the registry are indexed under Respiratory Distress Syndrome; 312 are open to participants now.

This study's enrollment of 9 is below the median of 60 across 961 interventional studies indexed under Respiratory Distress Syndrome.

Browse Respiratory Distress Syndrome studies →

Lead sponsor

Michael A. Matthay is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Patients will be eligible for inclusion if they meet all of the below criteria. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:

Acute onset (defined below) of:

  1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio \< 200 with at least 8 cm H2O positive end-expiratory airway pressure (PEEP)
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
  3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

In addition to meeting inclusion criteria, enrollment must occur within 96-hours of first meeting ARDS criteria per the Berlin definition of ARDS.

Exclusion criteria

Exclusion Criteria:

  1. Age less than 18 years
  2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
  3. Pregnant or breast-feeding
  4. Prisoner
  5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
  6. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  7. Moderate to severe liver failure (Childs-Pugh Score > 12)
  8. Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
  9. Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest).
  10. Major trauma in the prior 5 days
  11. Lung transplant patient
  12. No consent/inability to obtain consent
  13. Moribund patient not expected to survive 24 hours
  14. WHO Class III or IV pulmonary hypertension
  15. Documented deep venous thrombosis or pulmonary embolism within past 3 months
  16. No arterial line/no intent to place an arterial line
  17. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
  18. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
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Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
9 participants (actual)

Study arms

  • Experimental
    Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

    A dose-escalation with 3 cohorts with 3 subjects/cohort who receive doses of 1, 5 and 10 million cells/kg predicted body weight (PBW). Proceed from lower dose to next higher dose if no safety concerns for each cohort.

    Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

Interventions

  • BiologicalAllogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

    Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.

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What researchers measure

Primary outcomes

  1. Incidence of Pre-specified Infusion Associated Adverse Events

    Any of the following occurring within 6 h of mesenchymal stem-cell infusion: * Addition of a third vasopressor or an increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg per min * Phenylephrine: 100 μg per min * Dopamine: 10 μg/kg per min * Epinephrine: 0·1 μg/kg per min * Hypoxaemia requiring an increase in the fraction of inspired oxygen of ≥0·2 and increase in positive end-expiratory airway pressure level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95% * New cardiac arrhythmia requiring cardioversion * New ventricular tachycardia, ventricular fi brillation, or asystole * A clinical scenario consistent with transfusion incompatibility or transfusion-related infection * Cardiac arrest or death within 24 h of mesenchymal stem-cell infusion

    Time frame: 24 hours

Secondary outcomes

  1. Incidence of Severe Adverse Events (SAEs)

    The number of participants with a severe adverse event during the study was assessed.

    Time frame: Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.

  2. Ventilator Free Days at Study Day 28

    Ventilator Free Days (VFDs) to day 28 were defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject received assisted breathing at day 27 or died prior to day 28, a value of zero VFDs was given.

    Time frame: time of initiating unassisted breathing to day 28

  3. Duration of Vasopressor Use (Days)

    Days on vasopressor to day 28 after study enrollment

    Time frame: 28 days

  4. ICU Free Days to Day 28

    Time frame: 28 days after study enrollment

  5. Hospital Survival to Day 60

    The number of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.

    Time frame: 60 days after randomization

  6. Mortality at Hospital Discharge

    The number of patients expired at hospital discharge.

    Time frame: From study enrollment to Hospital discharge

07

Results

Posted Aug 14, 2017

Participant flow

This dose-escalation Phase 1 clinical trial with 3 cohorts with 3 subjects/cohort was performed in 7 centers in USA between July 2013 to January 2014.

Participant flow — Overall Study
MilestoneHuman Mesenchymal Stem Cells 1 Million Cells/kg PBWHuman Mesenchymal Stem Cells 5 Million Cells/kg PBWHuman Mesenchymal Stem Cells 10 Million Cells/kg PBW
Started333
Completed333
Not completed000

Outcome measures

PrimaryIncidence of Pre-specified Infusion Associated Adverse Events

Any of the following occurring within 6 h of mesenchymal stem-cell infusion: * Addition of a third vasopressor or an increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg per min * Phenylephrine: 100 μg per min * Dopamine: 10 μg/kg per min * Epinephrine: 0·1 μg/kg per min * Hypoxaemia requiring an increase in the fraction of inspired oxygen of ≥0·2 and increase in positive end-expiratory airway pressure level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95% * New cardiac arrhythmia requiring cardioversion * New ventricular tachycardia, ventricular fi brillation, or asystole * A clinical scenario consistent with transfusion incompatibility or transfusion-related infection * Cardiac arrest or death within 24 h of mesenchymal stem-cell infusion

Time frame:
24 hours
Reported as:
Number · participants
Incidence of Pre-specified Infusion Associated Adverse Events
participantsHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
Incidence of Pre-specified Infusion Associated Adverse Events000
SecondaryIncidence of Severe Adverse Events (SAEs)

The number of participants with a severe adverse event during the study was assessed.

Time frame:
Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.
Reported as:
Number · participants
Incidence of Severe Adverse Events (SAEs)
participantsHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
Incidence of Severe Adverse Events (SAEs)210
SecondaryVentilator Free Days at Study Day 28

Ventilator Free Days (VFDs) to day 28 were defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject received assisted breathing at day 27 or died prior to day 28, a value of zero VFDs was given.

Time frame:
time of initiating unassisted breathing to day 28
Reported as:
Median · day
Ventilator Free Days at Study Day 28
dayHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
Ventilator Free Days at Study Day 2818 (0 to 24)22 (0 to 27)20 (12 to 26)
SecondaryDuration of Vasopressor Use (Days)

Days on vasopressor to day 28 after study enrollment

Time frame:
28 days
Reported as:
Median · day
Duration of Vasopressor Use (Days)
dayHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
Duration of Vasopressor Use (Days)4 (0 to 10)2 (0 to 3)0 (0 to 0)
SecondaryICU Free Days to Day 28
Time frame:
28 days after study enrollment
Reported as:
Median · day
ICU Free Days to Day 28
dayHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
ICU Free Days to Day 2814 (0 to 24)21 (0 to 26)18 (9 to 22)
SecondaryHospital Survival to Day 60

The number of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.

Time frame:
60 days after randomization
Reported as:
Number · participants
Hospital Survival to Day 60
participantsHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
Hospital Survival to Day 60223
SecondaryMortality at Hospital Discharge

The number of patients expired at hospital discharge.

Time frame:
From study enrollment to Hospital discharge
Reported as:
Number · participants
Mortality at Hospital Discharge
participantsHuman Mesenchymal Stem Cells: 1 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cellls/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cellls/kg PBW
Mortality at Hospital Discharge110

Adverse events

Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Human Mesenchymal Stem Cells: 1 Million Cells/kg PBW—2/3 (66.7%)0/3 (0%)
Human Mesenchymal Stem Cells: 5 Million Cells/kg PBW—1/3 (33.3%)1/3 (33.3%)
Human Mesenchymal Stem Cells: 10 Million Cells/kg PBW—0/3 (0%)1/3 (33.3%)
Most frequent serious events
Most frequent serious events
EventHuman Mesenchymal Stem Cells: 1 Million Cells/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cells/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cells/kg PBW
Multiorgan failureRespiratory, thoracic and mediastinal disorders1/31/30/3
Infarcts of kidneys, spleen and brainVascular disorders1/30/30/3
Most frequent other events
Most frequent other events
EventHuman Mesenchymal Stem Cells: 1 Million Cells/kg PBWHuman Mesenchymal Stem Cells: 5 Million Cells/kg PBWHuman Mesenchymal Stem Cells: 10 Million Cells/kg PBW
Elevated liver function testsHepatobiliary disorders0/31/30/3
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/30/31/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
<=18 years0000
Between 18 and 65 years2237
>=65 years1102
Age, Continuous
Age, Continuous(years)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
Mean58.0 (29 to 86)58.3 (46 to 67)48.3 (38 to 55)54.9 (29 to 86)
Sex: Female, Male
Sex: Female, Male(Participants)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
Female3317
Male0022
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
Hispanic or Latino0202
Not Hispanic or Latino3137
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
American Indian or Alaska Native0000
Asian1001
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White2327
More than one race0000
Unknown or Not Reported0011
Region of Enrollment
Region of Enrollment(participants)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
United States3339
APACHE III Score
APACHE III Score(scores on a scale)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
Mean91.7 (62 to 111)89.7 (64 to 115)88.3 (54 to 108)89.9 (54 to 115)
Primary cause of ARDS
Primary cause of ARDS(participants)Human Mesenchymal Stem Cells 1 Million Cells/kg PBWMesenchymal Stem Cells 5 Million Cells/kg PBWMesenchymal Stem Cells 10 Million Cells/kg PBWTotal
Pneumonia1124
Aspiration1203
Sepsis0011
Pre-eclampsia1001
08

Study locations

4 sites
  • University of California San Francisco Medical Center
    San Francisco, California 94143, United States
  • Stanford University Medical Center
    Stanford, California 94305, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15213, United States
09

References and documents

Publications

  • Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17. PubMed 25529339 ↗
  • Liu KD, Wilson JG, Zhuo H, Caballero L, McMillan ML, Fang X, Cosgrove K, Calfee CS, Lee JW, Kangelaris KN, Gotts JE, Rogers AJ, Levitt JE, Wiener-Kronish JP, Delucchi KL, Leavitt AD, McKenna DH, Thompson BT, Matthay MA. Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome. Ann Intensive Care. 2014 Jul 3;4:22. doi: 10.1186/s13613-014-0022-z. eCollection 2014. PubMed 25593740 ↗
  • Asmussen S, Ito H, Traber DL, Lee JW, Cox RA, Hawkins HK, McAuley DF, McKenna DH, Traber LD, Zhuo H, Wilson J, Herndon DN, Prough DS, Liu KD, Matthay MA, Enkhbaatar P. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax. 2014 Sep;69(9):819-25. doi: 10.1136/thoraxjnl-2013-204980. Epub 2014 Jun 2. PubMed 24891325 ↗

Individual participant data

Plan to share: No

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 14, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01775774
Lead sponsor
Michael A. Matthay
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Massachusetts General Hospital, Stanford University, University of Pittsburgh, University of Minnesota
Responsible party
Michael A. Matthay (Prinicpal Investigator, University of California, San Francisco) — Sponsor-investigator
First posted
Jan 25, 2013
Start date
Jul 2013
Primary completion
Feb 2014
Completion
Feb 2015
Results posted
Aug 14, 2017
Last update
Aug 14, 2017

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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