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

NCT03059355 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 20170095
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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).

Conditions

Endothelial Dysfunction; Metabolic Syndrome; Chronic Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Cytokine Levels

  at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6

• hsCRP Levels

  at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6

• Stem Cell Factor (SCF) Levels

  at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6

• Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs)

  at Baseline, and at 3 months

• Flow Mediated Diameter Percentage (FMD%)

  at Baseline and at Month 3

Study Arms (7)

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.

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.

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.

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.

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.

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.

Biological: BMMSCs

Group C (Placebo)

PLACEBO COMPARATOR

Participants randomized to receive a single administration of placebo via peripheral intravenous infusion.

Other: Placebo

Interventions

UCMSCs BIOLOGICAL

Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs)

Group A (UCMSCs - 100 million); Pilot Phase: Group 1 (UCMSCs - 20 million); Pilot Phase: Group 3 (UCMSCs - 100 million)

BMMSCs BIOLOGICAL

Bone Marrow derived Mesenchymal Stem Cells (BMMSCs)

Group B (BMMSCs - 100 million); Pilot Phase: Group 2 (BMMSCs - 20 million); Pilot Phase: Group 4 (BMMSCs -100 million)

Placebo OTHER

a single administration of placebo delivered via peripheral intravenous infusion.

Group C (Placebo)

Eligibility Criteria

• Age: 21 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Joshua M Hare: lead
• The Marcus Foundation: collaborator

Study Sites (1)

ISCI / University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Related Links

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

MeSH Terms

Conditions

Metabolic Syndrome

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Joshua M Hare, MD
• Organization: University of Miami, Miller School of Medicine - Interdisciplinary Stem Cell Institute (ISCI)

JHare@med.miami.edu

305 243 5579

Study Officials

• Joshua M Hare, MD

  ISCI / University of Miami Miller School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Pilot phase is open-label. Randomized phase is blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of ISCI, Louis Lemberg Professor of Medicine

Study Record Dates

• First Submitted: February 6, 2017
• First Posted: February 23, 2017
• Study Start: April 12, 2018
• Primary Completion: March 23, 2020
• Study Completion: February 11, 2021
• Last Updated: November 8, 2022
• Results First Posted: November 8, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)