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

Joshua M Hare

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Endothelial Dysfunction; Chronic Inflammation; Metabolic Syndrome

Treatments: Biological: UCMSCs; Biological: BMMSCs; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03059355

20170095

Details and patient eligibility

About

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).

Enrollment: 14 patients

Sex: All

Ages: 21 to 95 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

14 participants in 7 patient groups, including a placebo group

Pilot Phase: Group 1 (UCMSCs - 20 million)

Experimental group

Description:

Three (3) subjects will be treated with a single administration of 2 x 10\^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.

Treatment:

Biological: UCMSCs

Pilot Phase: Group 3 (UCMSCs - 100 million)

Experimental group

Description:

Three (3) subjects will be treated with a single IV administration of 1 x 10\^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.

Treatment:

Biological: UCMSCs

Pilot Phase: Group 2 (BMMSCs - 20 million)

Experimental group

Description:

Three (3) subjects will be treated with a single IV administration of 2 x 10\^7 (20 million) BMMSCs delivered via peripheral intravenous infusion.

Treatment:

Biological: BMMSCs

Pilot Phase: Group 4 (BMMSCs -100 million)

Experimental group

Description:

Three (3) subjects will be treated with a single IV administration of 1 x 10\^8 (100 million) BMMSCs delivered via peripheral intravenous infusion.

Treatment:

Biological: BMMSCs

Group A (UCMSCs - 100 million)

Experimental group

Description:

Participants randomized to receive a single administration of 1 x 10\^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.

Treatment:

Biological: UCMSCs

Group B (BMMSCs - 100 million)

Experimental group

Description:

Participants randomized to receive a single administration of 1 x 10\^8 (100 million) BMMSC delivered via peripheral intravenous infusion.

Treatment:

Biological: BMMSCs

Group C (Placebo)

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo