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

Metabolic Syndrome Clinical Trial

— CERES  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03059355
• Other study ID #: 20170095
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 12, 2018
• Est. completion date: February 11, 2021

Study information

• Verified date: October 2022
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: February 11, 2021
• Est. primary completion date: March 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 95 Years

Eligibility

Inclusion Criteria:

• 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:

• 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

Exclusion Criteria:

• 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.

• 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.

Related Conditions & MeSH terms

• Chronic Inflammation
• Endothelial Dysfunction
• Inflammation
• Metabolic Syndrome
• Syndrome

Intervention

Biological:
• UCMSCs
Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)
• BMMSCs
Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)

Other:
• Placebo
a single administration of placebo delivered via peripheral intravenous infusion.

Locations

Country	Name	City	State
United States	ISCI / University of Miami Miller School of Medicine	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Joshua M Hare	The Marcus Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	one month post infusion
Secondary	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 (TNFa), and Vascular Endothelial Growth Factor (VEGF), & Stromal Cell Derived Factor (SDF-1a) levels from serum/plasma samples all measured in pg/mL.	at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Secondary	hsCRP Levels	values at baseline and follow up for the following inflammatory marker: Serum High sensitivity C-Reactive Protein (hsCRP) in mg/L.	at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Secondary	Stem Cell Factor (SCF) Levels	SCF levels from serum/plasma samples measured in units of mg/mL	at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Secondary	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	at Baseline, and at 3 months
Secondary	Flow Mediated Diameter Percentage (FMD%)	FMD% will be assessed using brachial artery ultrasound	at Baseline and at Month 3

External Links

•   Interdisciplinary Stem Cell Institute at the University of Miami Miller School website