Acute Respiratory Distress SyndromePhase 1STARTNCT01775774
Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome
A Phase 1 study testing Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells in people with Acute Respiratory Distress Syndrome, run by Michael A. Matthay at 4 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2013to Feb 2015
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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)
- Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
- 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.
Who cannot join
- Age less than 18 years
- Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
- Pregnant or breast-feeding
- Prisoner
- Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
- Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
Show all 18Show fewer
- Moderate to severe liver failure (Childs-Pugh Score > 12)
- Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
- 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).
- Major trauma in the prior 5 days
- Lung transplant patient
- No consent/inability to obtain consent
- Moribund patient not expected to survive 24 hours
- WHO Class III or IV pulmonary hypertension
- Documented deep venous thrombosis or pulmonary embolism within past 3 months
- No arterial line/no intent to place an arterial line
- No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
- Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
University of California San Francisco Medical Center
San Francisco, California, 94143
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: A Phase 1 Multi-center Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stem Cells for the Treatment of Acute Respiratory Distress Syndrome
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.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
- Keywords
- Acute Respiratory Distress Syndrome, Acute Lung Injury, Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
- Medical subject headings
- Respiratory Distress Syndrome, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem CellsBiological
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells | Experimental | 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. Receives: Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 hours
Secondary outcomes (6)
Incidence of Severe Adverse Events (SAEs)
The number of participants with a severe adverse event during the study was assessed.
Measured: Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.
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.
Measured: time of initiating unassisted breathing to day 28
Duration of Vasopressor Use (Days)
Days on vasopressor to day 28 after study enrollment
Measured: 28 days
ICU Free Days to Day 28
Measured: 28 days after study enrollment
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.
Measured: 60 days after randomization
Mortality at Hospital Discharge
The number of patients expired at hospital discharge.
Measured: From study enrollment to Hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2013 (estimated)
- Study startJul 2013
- Primary completionFeb 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael A. Matthay
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Massachusetts General Hospital, Stanford University, University of Pittsburgh, University of Minnesota
- Responsible party
- Sponsor-investigator, Michael A. Matthay, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01775774
- Sponsor's protocol ID
- ARDS MSC 001
- Other IDs
- 1U01HL108713-01
- Acronym
- START
- Status last verified
- May 2017
- First submitted
- 18 Jan 2013
- Last updated
- 14 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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 25529339Liu 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 25593740Asmussen 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
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Multi-center Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stem Cells for the Treatment of Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT01775774
- Acronym / sponsor ID
- START / ARDS MSC 001
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Acute Respiratory Distress Syndrome, Acute Lung Injury, Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Michael A. MatthayUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Massachusetts General Hospital, Stanford University, University of Pittsburgh, University of Minnesota
- Study start
- Jul 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 25 Jan 2013 (estimated)
- Results
- Posted 14 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells | Experimental | Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem CellsA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- 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)
- Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
- 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.
Key exclusion criteria (18 listed)
- Age less than 18 years
- Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
- Pregnant or breast-feeding
- Prisoner
- Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic Bone Marrow-Derived Human Mesenchymal Stem CellsAllogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously. | Biological | Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells |
Primary outcome
Incidence of Pre-specified Infusion Associated Adverse Events
Time frame: 24 hours
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
6 secondary outcomes
Incidence of Severe Adverse Events (SAEs)
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.
Ventilator Free Days at Study Day 28
Time frame: time of initiating unassisted breathing to day 28
Duration of Vasopressor Use (Days)
Time frame: 28 days
ICU Free Days to Day 28
Time frame: 28 days after study enrollment
Hospital Survival to Day 60
Time frame: 60 days after randomization
Mortality at Hospital Discharge
Time frame: From study enrollment to Hospital discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25529339Wilson 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.
- Derived from this study: PubMed 25593740Liu 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.
- Derived from this study: PubMed 24891325Asmussen 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells in people with Acute Respiratory Distress Syndrome, run by Michael A. Matthay at 4 sites 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 6 inclusion and 18 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 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 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.
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 14 Aug 2017). 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 Pre-specified Infusion Associated Adverse Events (time frame: 24 hours). 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 NCT01775774, 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 Aug 2017.