Endothelial DysfunctionPhase 1/2CERESNCT03059355

Infusion of Umbilical Cord Versus Bone Marrow Derived Mesenchymal Stem Cells to Evaluate Cytokine Suppression.

A Phase 1/2 study testing UCMSCs and BMMSCs in people with Endothelial Dysfunction and Metabolic Syndrome, run by Joshua M Hare at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study is to compare the safety and efficacy of UCMSCs and BMMSCs administered intravenously in patients to evaluate cytokine suppression in patients with chronic inflammation. Cells administered via intravenous infusion (IV) and will be tested in 37 patients in two phases (Pilot and Randomized). Read more about this study

Who is it for?: Ages 21 to 95 years
Conditions the study is for: Endothelial Dysfunction, Metabolic Syndrome, Chronic Inflammation
What is being tested?: UCMSCs and BMMSCs
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 12 Apr 2018to 11 Feb 2021
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 21 to 95 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provide written informed consent
Subjects age > 21 and < 95 years at the time of signing the Informed Consent Form.
Each subject must have endothelial dysfunction.
Endothelial dysfunction Criteria:
Impaired flow-mediated vasodilation (FMD <7%)
At the time of enrollment, each subject must meet at least 3 out of the 5 criteria under the harmonized definition of the metabolic syndrome, consisting of the following:

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Waist circumference - US defined: ≥ 102 cm (males) or ≥ 88 cm (females)
Elevated triglycerides - ≥ 150 mg/dL (1.7 mM)
Reduced HDL-C - Males: <40 mg/dL (1.0 mM) Females: <50 mg/dL (1.3 mM)
Elevated blood pressure - Systolic ≥ 130 mm Hg and/or Diastolic ≥ 85 mm Hg
Elevated fasting glucose - ≥ 100 mg/dL

Who cannot join

Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion.
Inability to perform any of the assessments required for endpoint analysis.
Active listing (or expected future listing) for transplant of any organ.
Clinically important abnormal screening laboratory values, as determined by the P.I.
Serious comorbid illness or any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study.
Have known allergies to penicillin or streptomycin.

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Hypersensitivity to dimethyl sulfoxide (DMSO).
Be a solid organ transplant recipient. This does not include prior cell-based therapy (>12 months prior enrollment) bone, skin, ligament, tendon or corneal grafting. Have a history of organ or cell transplant rejection.
Have a clinical history of malignancy within 3 years (i.e., subjects with prior malignancy must be disease free for 3 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.
History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months.
Be serum positive for HIV, hepatitis B surface antigen or Viremic hepatitis C, and/or Syphilis.
Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
Patients with Ejection Fraction <45% (heart failure patients).
Glomerular Filtration Rate < or equal to 35 (chronic kidney disease stage 3 or higher).
Liver disease (elevated Liver Function Tests greater than 3x normal limit).
Advanced pulmonary disease (requiring home oxygen and/or less than 1 expected life span).
Proliferative diabetic retinopathy
Hemoglobin A1C greater than 7.

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, Placebo-controlled Comparative Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Bone Marrow (BM) Derived MSCs to Evaluate Cytokine Suppression in Patients With Chronic Inflammation Due to Metabolic Syndrome.

Conditions: Endothelial Dysfunction, Metabolic Syndrome, Chronic Inflammation
Being tested: UCMSCs, BMMSCs, Placebo
Medical subject headings: Metabolic Syndrome

What participants receive

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

UCMSCsBiological
Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)
BMMSCsBiological
Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)
PlaceboOther
a single administration of placebo delivered via peripheral intravenous infusion.

Study groups in NCT03059355
Study group	Role	What they receive
Pilot Phase: Group 1 (UCMSCs - 20 million)	Experimental	Three (3) subjects will be treated with a single administration of 2 x 10^7 (20 million) UCMSCs delivered via peripheral intravenous infusion. Receives: Biological: UCMSCs
Pilot Phase: Group 3 (UCMSCs - 100 million)	Experimental	Three (3) subjects will be treated with a single IV administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion. Receives: Biological: UCMSCs
Pilot Phase: Group 2 (BMMSCs - 20 million)	Experimental	Three (3) subjects will be treated with a single IV administration of 2 x 10^7 (20 million) BMMSCs delivered via peripheral intravenous infusion. Receives: Biological: BMMSCs
Pilot Phase: Group 4 (BMMSCs -100 million)	Experimental	Three (3) subjects will be treated with a single IV administration of 1 x 10^8 (100 million) BMMSCs delivered via peripheral intravenous infusion. Receives: Biological: BMMSCs
Group A (UCMSCs - 100 million)	Experimental	Participants randomized to receive a single administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion. Receives: Biological: UCMSCs
Group B (BMMSCs - 100 million)	Experimental	Participants randomized to receive a single administration of 1 x 10^8 (100 million) BMMSC delivered via peripheral intravenous infusion. Receives: Biological: BMMSCs
Group C (Placebo)	Placebo comparator	Participants randomized to receive a single administration of placebo via peripheral intravenous infusion. Receives: Other: Placebo

What is being measured

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

Number of Treatment-Emergent Serious Adverse Events (TE-SAEs)
Number of treatment-emergent serious adverse events (SAE) (at one-month post infusion), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities, determined per the Investigator's judgment.
Measured: one month post infusion

Secondary outcomes (5)

Cytokine Levels
Cytokine levels including the following panel of inflammatory and angiogenic markers: Interleukin-1 (IL-1), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNFα), and Vascular Endothelial Growth Factor (VEGF), \& Stromal Cell Derived Factor (SDF-1a) levels from serum/plasma samples all measured in pg/mL.
Measured: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
hsCRP Levels
values at baseline and follow up for the following inflammatory marker: Serum High sensitivity C-Reactive Protein (hsCRP) in mg/L.
Measured: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Stem Cell Factor (SCF) Levels
SCF levels from serum/plasma samples measured in units of mg/mL
Measured: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs)
Endothelial function will be reported as the change in Endothelial Progenitor Cell Colony Forming Unit (EPC-CFU) assessed via blood sample assay
Measured: at Baseline, and at 3 months
Flow Mediated Diameter Percentage (FMD%)
FMD% will be assessed using brachial artery ultrasound
Measured: at Baseline and at Month 3

Timeline

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

12 Apr 201811 Feb 2021

First posted23 Feb 2017
Study start12 Apr 2018
Primary completion23 Mar 2020
Study completion11 Feb 2021

Why it stopped: COVID-19 Pandemic and lack of funding

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.
Other trials for Endothelial DysfunctionStudies 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 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03059355
Sponsor's protocol ID: 20170095
Acronym: CERES
Status last verified: Oct 2022
First submitted: 6 Feb 2017
Last updated: 8 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Endothelial Dysfunction trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II, Randomized, Placebo-controlled Comparative Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Bone Marrow (BM) Derived MSCs to Evaluate Cytokine Suppression in Patients With Chronic Inflammation Due to Metabolic Syndrome.
ClinicalTrials.gov ID: NCT03059355
Acronym / sponsor ID: CERES / 20170095
Conditions: Endothelial Dysfunction, Metabolic Syndrome, Chronic Inflammation
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: COVID-19 Pandemic and lack of funding
Enrolment: 14 participants (actual)
Lead sponsor: Joshua M HareUniversity, hospital or other
Collaborators: The Marcus Foundation
Study start: 12 Apr 2018 (actual)
Primary completion: 23 Mar 2020 (actual)
Study completion: 11 Feb 2021 (actual)
First posted: 23 Feb 2017 (actual)
Results: Posted 8 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 7

Arm	Type	Receives
Pilot Phase: Group 1 (UCMSCs - 20 million)	Experimental	Biological: UCMSCsThree (3) subjects will be treated with a single administration of 2 x 10^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.
Pilot Phase: Group 3 (UCMSCs - 100 million)	Experimental	Biological: UCMSCsThree (3) subjects will be treated with a single IV administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
Pilot Phase: Group 2 (BMMSCs - 20 million)	Experimental	Biological: BMMSCsThree (3) subjects will be treated with a single IV administration of 2 x 10^7 (20 million) BMMSCs delivered via peripheral intravenous infusion.
Pilot Phase: Group 4 (BMMSCs -100 million)	Experimental	Biological: BMMSCsThree (3) subjects will be treated with a single IV administration of 1 x 10^8 (100 million) BMMSCs delivered via peripheral intravenous infusion.
Group A (UCMSCs - 100 million)	Experimental	Biological: UCMSCsParticipants randomized to receive a single administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
Group B (BMMSCs - 100 million)	Experimental	Biological: BMMSCsParticipants randomized to receive a single administration of 1 x 10^8 (100 million) BMMSC delivered via peripheral intravenous infusion.
Group C (Placebo)	Placebo comparator	Other: PlaceboParticipants randomized to receive a single administration of placebo via peripheral intravenous infusion.

Who may qualify

Ages: 21 to 95 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Provide written informed consent
Subjects age > 21 and < 95 years at the time of signing the Informed Consent Form.
Each subject must have endothelial dysfunction.
Impaired flow-mediated vasodilation (FMD <7%)
At the time of enrollment, each subject must meet at least 3 out of the 5 criteria under the harmonized definition of the metabolic syndrome, consisting of the following:

Key exclusion criteria (19 listed)

Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion.
Inability to perform any of the assessments required for endpoint analysis.
Active listing (or expected future listing) for transplant of any organ.
Clinically important abnormal screening laboratory values, as determined by the P.I.
Serious comorbid illness or any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study.

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
UCMSCsAllogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)	Biological	Group A (UCMSCs - 100 million), Pilot Phase: Group 1 (UCMSCs - 20 million), Pilot Phase: Group 3 (UCMSCs - 100 million)
BMMSCsBone Marrow derived Mesenchymal Stem Cells (BMMSCs)	Biological	Group B (BMMSCs - 100 million), Pilot Phase: Group 2 (BMMSCs - 20 million), Pilot Phase: Group 4 (BMMSCs -100 million)
Placeboa single administration of placebo delivered via peripheral intravenous infusion.	Other	Group C (Placebo)

Primary outcome

Number of Treatment-Emergent Serious Adverse Events (TE-SAEs)
Time frame: one month post infusion
Number of treatment-emergent serious adverse events (SAE) (at one-month post infusion), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities, determined per the Investigator's judgment.

5 secondary outcomes

Cytokine Levels
Time frame: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
hsCRP Levels
Time frame: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Stem Cell Factor (SCF) Levels
Time frame: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs)
Time frame: at Baseline, and at 3 months
Flow Mediated Diameter Percentage (FMD%)
Time frame: at Baseline and at Month 3

Results and safety

Results posted to the registry on 8 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pilot Phase: Group 1 (UCMSCs - 20 Million)	3	3
Pilot Phase: Group 2 (BMMSCs - 20 Million)	3	3
Pilot Phase: Group 3 (UCMSCs - 100 Million)	3	3
Pilot Phase: Group 4 (BMMSCs -100 Million)	3	3
Group A (UCMSCs - 100 Million)	0	0
Group B (BMMSCs - 100 Million)	2	2
Group C (Placebo)	0	0

Primary outcome: Number of Treatment-Emergent Serious Adverse Events (TE-SAEs)

Time frame: one month post infusion. Number. Unit: Events

Measure	Pilot Phase: Group 1 (UCMSCs - 20 Million) n = 3	Pilot Phase: Group 2 (BMMSCs - 20 Million) n = 3	Pilot Phase: Group 3 (UCMSCs - 100 Million) n = 3	Pilot Phase: Group 4 (BMMSCs -100 Million) n = 3	Group A (UCMSCs - 100 Million) n = 0	Group B (BMMSCs - 100 Million) n = 2	Group C (Placebo) n = 0
Value	0	0	0	0	–	0	–

Population analysed: No subjects had been randomized to Group A or C at the time of trial termination.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pilot Phase: Group 1 (UCMSCs - 20 Million)	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Pilot Phase: Group 2 (BMMSCs - 20 Million)	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Pilot Phase: Group 3 (UCMSCs - 100 Million)	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Pilot Phase: Group 4 (BMMSCs -100 Million)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Group A (UCMSCs - 100 Million)	0 of 0	0 of 0	0
Group B (BMMSCs - 100 Million)	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Group C (Placebo)	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): Funding timeline was not met due to the coronavirus disease 2019 (COVID-19) pandemic. No additional funding was provided, therefore the study had to be terminated early.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Interdisciplinary Stem Cell Institute at the University of Miami Miller School websiteLink provided by the sponsor.
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.

Joshua M Hare, MD principal investigator

ISCI / University of Miami Miller School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing UCMSCs and BMMSCs in people with Endothelial Dysfunction and Metabolic Syndrome, run by Joshua M Hare 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 11 inclusion and 19 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: stopped early, as of the sponsor's last update on 8 Nov 2022. 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. Some participants in this study may receive a placebo. 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 8 Nov 2022). 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?

Number of 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 NCT03059355.

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 8 Nov 2022.