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

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.

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).

Study Overview

• Status: Terminated
• Conditions: Metabolic Syndrome; Endothelial Dysfunction; Chronic Inflammation
• Intervention / Treatment: Biological: UCMSCs; Biological: BMMSCs; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • ISCI / University of Miami Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 95 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pilot Phase: Group 1 (UCMSCs - 20 million); Three (3) subjects will be treated with a single administration of 2 x 10^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.	Biological: UCMSCs; Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)
EXPERIMENTAL: Pilot Phase: Group 3 (UCMSCs - 100 million); Three (3) subjects will be treated with a single IV administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.	Biological: UCMSCs; Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)
EXPERIMENTAL: Pilot Phase: Group 2 (BMMSCs - 20 million); Three (3) subjects will be treated with a single IV administration of 2 x 10^7 (20 million) BMMSCs delivered via peripheral intravenous infusion.	Biological: BMMSCs; Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)
EXPERIMENTAL: Pilot Phase: Group 4 (BMMSCs -100 million); Three (3) subjects will be treated with a single IV administration of 1 x 10^8 (100 million) BMMSCs delivered via peripheral intravenous infusion.	Biological: BMMSCs; Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)
EXPERIMENTAL: Group A (UCMSCs - 100 million); Participants randomized to receive a single administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.	Biological: UCMSCs; Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)
EXPERIMENTAL: Group B (BMMSCs - 100 million); Participants randomized to receive a single administration of 1 x 10^8 (100 million) BMMSC delivered via peripheral intravenous infusion.	Biological: BMMSCs; Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)
PLACEBO_COMPARATOR: Group C (Placebo); Participants randomized to receive a single administration of placebo via peripheral intravenous infusion.	Other: Placebo; a single administration of placebo delivered via peripheral intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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	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	at Baseline, and at 3 months
Flow Mediated Diameter Percentage (FMD%)	FMD% will be assessed using brachial artery ultrasound	at Baseline and at Month 3

Collaborators and Investigators

• Sponsor: Joshua M Hare
• Collaborators: The Marcus Foundation

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 12, 2018
• Primary Completion (ACTUAL): March 23, 2020
• Study Completion (ACTUAL): February 11, 2021

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (ACTUAL): February 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Inflammation; Metabolic Syndrome
• Other Study ID Numbers: 20170095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No