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

• ClinicalTrials.gov Identifier: NCT03059355
• Recruitment Status: Active, not recruiting
• First Posted: February 23, 2017
• Last Update Posted: October 28, 2020
• Sponsor: Joshua M Hare
• Information provided by (Responsible Party): Joshua M Hare, University of Miami

Tracking Information

• First Submitted Date: February 6, 2017
• First Posted Date: February 23, 2017
• Last Update Posted Date: October 28, 2020
• Actual Study Start Date: April 12, 2018
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2017)

Incidence of any treatment-emergent serious adverse events (TE-SAEs) [ Time Frame: one month post infusion ]

Incidence (at one-month post infusion) of any treatment-emergent serious adverse events (TE-SAEs), 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 15, 2017)

• Change of inflammatory markers [ Time Frame: Baseline and at 6 months ]
  Change between baseline and 6 months for the following panel of inflammatory markers: C-reactive protein, Interleukin-6, D-dimer, fibrinogen, Complete blood count with differential, and TNFα.
• Effect on Frailty Phenotype Score [ Time Frame: baseline, 3 and 6 months' follow-up visits ]
  to measure if intervention with UCMSCs versus BMMSCs has a beneficial effect on Cardiovascular Health Study (CHS) Frailty Phenotype Score.
• Effect on Physical Performance through Quality of Life questionnaires [ Time Frame: baseline, 3 and 6 months' follow-up visits ]
  to measure if intervention with UCMSCs versus BMMSCs has a beneficial effect on physical performance by comparing quality of life questionnaires.
• Change of Pro-inflammatory cytokines in laboratory analysis [ Time Frame: baseline, 3 and 6 months' follow-up visits ]
  to measure if intervention with UCMSCs versus BMMSCs reduces pro-inflammatory cytokines, and the relationship between these cytokines. Assess change for the following panel of inflammatory markers: CRP, IL-6, D-dimer, fibrinogen, CBC with differential, and TNFα.
• Determine if there is an improvement in symptoms between subjects receiving umbilical cord cells versus bone marrow cells [ Time Frame: baseline, 3 and 6 months' follow-up visits ]
  to measure if intervention with UCMSCs versus BMMSCs improves composite clinical outcomes / symptoms in congestive heart failure subjects.
• Number of study participants experiencing safety events (difference between dose and placebo subjects) [ Time Frame: baseline, 3 and 6 months' follow-up visits ]
  To measure the safety of three doses of UCMSCs versus BMMSCs compared to placebo in congestive heart failure.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Infusion of Umbilical Cord Versus Bone Marrow Derived Mesenchymal Stem Cells to Evaluate Cytokine Suppression.
• 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.
• Brief 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).

Detailed Description

In this Study, cells administered via intravenous infusion (IV) will be tested in 37 patients in two phases (Pilot and Randomized):

The pilot phase will consist of 12 subjects and the randomized phase will consist of 25 subjects.

Subjects in each pilot phase group (Group 1, 2, 3 and 4) will not be treated less than 5 days apart and will each undergo full evaluation post infusion to demonstrate there is no evidence of treatment emergent SAE's prior to proceeding with the treatment of further subjects.

For subjects randomized to Group 3, 4, C and D (BMMSCs); the cells will be derived from a sample of the subject's bone marrow (obtained by iliac crest aspiration) approximately 4-6 weeks prior to infusion.

Duration of Study Participation will be 12 months (Follow-up will be at 2 weeks, 1 Month, 3, 6, and 12 months.)

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Endothelial Dysfunction
• Metabolic Syndrome
• Chronic Inflammation

Intervention

• Biological: UCMSCs
  Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)
• Biological: BMMSCs
  Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)
• Other: Placebo
  a single administration of placebo delivered via peripheral intravenous infusion.

Study Arms

• Experimental: Pilot Phase: Group 1 (UCMSCs)
  Three (3) subjects will be treated with a single administration of 2 x 10^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.
  Intervention: Biological: UCMSCs
• Experimental: Pilot Phase: Group 2 (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.
  Intervention: Biological: UCMSCs
• Experimental: Pilot Phase: Group 3 (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.
  Intervention: Biological: 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.
  Intervention: Biological: BMMSCs
• Experimental: Group A (UCMSCs - 20 Million)
  Five (5) subjects will be treated with a single administration of 2 x 10^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.
  Intervention: Biological: UCMSCs
• Experimental: Group B (UCMSCs - 100 million)
  Five (5) subjects will be treated with a single administration of 1 x 10^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
  Intervention: Biological: UCMSCs
• Experimental: Group C (BMMSCs - 20 million)
  Five (5) subjects will be treated with a single administration of 2 x 10^7 (20 million) BMMSCs delivered via peripheral intravenous infusion.
  Intervention: Biological: BMMSCs
• Experimental: Group D (BMMSCs - 100 million)
  Five (5) subjects will be treated with a single administration of 1 x 10^8 (100 million) BMMSC delivered via peripheral intravenous infusion.
  Intervention: Biological: BMMSCs
• Placebo Comparator: Group E (Placebo)
  Five (5) subjects will be treated with a single administration of placebo delivered via peripheral intravenous infusion.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 16, 2020): 19
• Original Estimated Enrollment (submitted: February 15, 2017): 37
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 BsAg or Viremic hepatitis C, and/or Syphilis - VDRL (Confirmation with FTA-ABS if needed (Syphilis)).
• Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
• Patients with EF<45% (heart failure patients).
• GFR < or equal to 35 (chronic kidney disease stage 3 or higher).
• Liver disease (elevated LFTs 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03059355
• Other Study ID Numbers: 20170095
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Joshua M Hare, University of Miami
• Study Sponsor: Joshua M Hare
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joshua M Hare, MD; ISCI / University of Miami Miller School of Medicine

• PRS Account: University of Miami
• Verification Date: October 2020