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A Study to Assess the Effect of Intravenous Dose of (aMBMC) to Subjects With Non-ischemic Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02467387
Recruitment Status : Completed
First Posted : June 10, 2015
Results First Posted : January 7, 2020
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Stemedica Cell Technologies, Inc.
Information provided by (Responsible Party):
CardioCell LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Non-Ischemic Heart Failure
Interventions Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)
Drug: Lactated Ringer's Solution
Enrollment 23
Recruitment Details 34 patients have been screened for eligibility between June, 2014 and April, 2016 at Emory University Medical Center, Atlanta, GA, Northwestern University Medical Center, Chicago, IL, University of Pennsylvania Medical Center, Philadelphia, PA, and Stony Brook University Medical Center, Stony Brook, NY.
Pre-assignment Details 23 out of 34 patients have been randomized and 22 received the study intervention. Of those not randomized, 10 did not meet inclusion criteria and 1 could not tolerate CMR.
Arm/Group Title itMSC, Then Placebo Placebo, Then itMSC
Hide Arm/Group Description Participants first received itMSC 1.5 million per kilogram of weight, infused in the corresponding hospital facility at speed of 1 mL/minute (cell concentration 1 million/mL). After 90 days patients completed treatment at 90 days, and thus constituted the control treatment. After 90 day follow-up testing patients received Placebo and followed up for another 90 days. Total efficacy follow-up - 180 days. Safety measurements 0, 60, 90, days 270 and 450. Participants first received Placebo, infused in the corresponding hospital facility at speed of 1 mL/minute. After 90 days patients completed Placebo Control and related testing, and received itMSC treatment 1.5 million per kilogram of weight, and thus constituted the itMSC treated group for another 90 days.Total efficacy follow-up - 180 days. Safety measurements 0, 60, 90, days 270 and 450.
Period Title: First Intervention
Started 11 12
Received Treatment as Randomized 10 12
Completed 10 12
Not Completed 1 0
Period Title: Second Intervention
Started 10 12
Completed 7 12
Not Completed 3 0
Arm/Group Title Study Population
Hide Arm/Group Description

itMSC, then Placebo: Participants first received itMSC 1.5 million per kilogram of weight, infused in the corresponding hospital facility at speed of 1 mL/minute (cell concentration 1 million/mL). After 90 days patients completed treatment at 90 days, and thus constituted the control treatment. After 90 day follow-up testing patients received Placebo and followed up for another 90 days. Total efficacy follow-up - 180 days. Safety follow-up - 240 days.

Placebo, then itMSC: Participants first received Placebo, infused in the corresponding hospital facility at speed of 1 mL/minute. After 90 days patients completed Placebo Control and related testing, and received itMSC treatment 1.5 million per kilogram of weight, and thus constituted the itMSC treated group for another 90 days.Total efficacy follow-up - 180 days. Safety follow-up - 240 days. and thus constituted the control treatment.

Overall Number of Baseline Participants 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants
47.3  (12.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Female
9
  40.9%
Male
13
  59.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
7
  31.8%
White
15
  68.2%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 22 participants
92.5  (19.96)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 22 participants
32.24  (7.56)
New York Heart Association (NYHA) Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Class II
21
  95.5%
Class III
1
   4.5%
[1]
Measure Description:

NYHA Class:

Class I (Mild): Patients with cardiac disease but without resulting in limitation of physical activity.

Class II (Mild): Cardiac disease resulting in slight limitation of physical activity.

Class III (Moderate): Cardiac disease resulting in marked limitation of physical activity.

Class IV (Severe): Cardiac disease resulting in the inability to carry on any physical activity without discomfort.

Improvement in NYHA classification was analyzed using logistic regression with treatment and group assignment (itMSC – placebo vs. placebo – itMSC) as covariates.

Systolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 22 participants
120  (17.1)
Diastolic Blood Pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 22 participants
74  (9.6)
Heart Rate  
Mean (Standard Deviation)
Unit of measure:  Bpm
Number Analyzed 22 participants
78  (14.2)
N-terminlal-proB-type Natriuretic Peptide (NT-proBNP)  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 22 participants
212  (841)
Troponin I  
Mean (Standard Deviation)
Unit of measure:  ug/mL
Number Analyzed 22 participants
0.0009  (0.0003)
Serum Sodium  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 22 participants
138  (2)
Serum Creatinine  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 22 participants
0.96  (0.23)
Aspartate Aminotransferase (AST)  
Mean (Standard Deviation)
Unit of measure:  International Units/milliliter (IU/mL)
Number Analyzed 22 participants
21.86  (8.64)
Alanine Aminotransferase (ALT)  
Mean (Standard Deviation)
Unit of measure:  IU/L
Number Analyzed 22 participants
21.82  (9.57)
Total bilirubin  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 22 participants
0.8  (0.4)
Albumin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 22 participants
4.2  (0.36)
History of Hypertension  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
5
  22.7%
History of Diabetes  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
3
  13.6%
History of Atrial Fibrillation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
2
   9.1%
History of Kidney Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
1
   4.5%
Left Ventricular Ejection Fraction (LVEF)  
Mean (Standard Deviation)
Unit of measure:  %
Number Analyzed 22 participants
31.6  (9.8)
Left Ventricular End Systolic Volume (LVESV)  
Mean (Standard Deviation)
Unit of measure:  mL
Number Analyzed 22 participants
189.6  (114.2)
Left Ventricular End-Diastolic Volume (LVEDV)  
Mean (Standard Deviation)
Unit of measure:  mL
Number Analyzed 22 participants
264.9  (120.4)
Loop diuretic medication  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
16
  72.7%
angiotensin converting enzyme inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARB) medication  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
22
 100.0%
Mineralocorticoid Receptor Antagonist medication  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
18
  81.8%
Beta-blocker  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
22
 100.0%
1.Primary Outcome
Title Safety Will be Evaluated by Number of AE
Hide Description As identified in the SAP, the safety analysis was the primary objective and was evaluated by the number of AEs
Time Frame Total AEs and SAEs within 450 days post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
All 22 participants that received itMSC treatment were included. All adverse events are divided into serious and non-serious.
Arm/Group Title Experimental Placebo
Hide Arm/Group Description:
Participants received itMSC
Participants received Placebo
Overall Number of Participants Analyzed 22 20
Measure Type: Number
Unit of Measure: number of events
Adverse Events 38 35
Serious Adverse Events 1 1
Cell related adverse events 1 0
All-cause hospitalization 0 0
All-cause death 0 0
2.Secondary Outcome
Title Change in LVEF From Baseline to Day 90 Post-initial Infusion.
Hide Description The secondary efficacy endpoint was the change in LVEF from baseline to Day 90 post-initial infusion. Participants with data available at each time point.
Time Frame Baseline to Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary efficacy endpoint according to the protocol was the change in LVEF from baseline to Day 90 post-initial infusion.
Arm/Group Title Experimental: Human (itMSC) Placebo:Lactated Ringer's Solution (LRS)
Hide Arm/Group Description:

Intervention: One time intravenous infusion of 1.5 million (aMBMC) per kg administered at approximately 2mL/min. Maximum dose as for 100kg subject or 150 million cells for any subject 100kg or more.

Allogeneic Mesenchymal Bone Marrow Cells (itMSC): One time infusion Allogeneic Mesenchymal Bone Marrow Cells (itMSC) 1.5 million cells/kg.

Intervention: One time intravenous infusion of 1.5mL/kg Lactated Ringer's Solution (LRS) administered at a constant rate of approximately 2mL/min.

Lactated Ringer's Solution: One time infusion 1.5mL/kg

Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: percentage of ejection volume
Baseline (%) Number Analyzed 12 participants 12 participants
34.3  (7.91) 34.5  (7.49)
90 days (%) Number Analyzed 9 participants 12 participants
34.1  (9.7) 36.7  (5.42)
Time Frame 450 days
Adverse Event Reporting Description

All AE summaries were restricted to treatment-emergent adverse events (TEAEs), and TEAEs were defined as those AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study.

Treatment-emergent AEs by severity (severe, other), relationship to study treatment (“related” or “not related”). Reported treshold 5%.

 
Arm/Group Title Experimental Placebo
Hide Arm/Group Description Subjects that received experimental drug, 22 subjects Subjects that received placebo, 20 subjects
All-Cause Mortality
Experimental Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)      0/20 (0.00%)    
Hide Serious Adverse Events
Experimental Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/22 (4.55%)      1/20 (5.00%)    
Cardiac disorders     
atrial fibrillation  1  1/22 (4.55%)  1 1/20 (5.00%)  1
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Experimental Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/22 (81.82%)      15/20 (75.00%)    
General disorders     
General Disorders and administration site condition: chest pain, fatigue, pyrexia  1  3/22 (13.64%)  11/20 (55.00%) 
Infections and infestations     
Upper Respiratory Tract, Nasopharyngitis  1  3/22 (13.64%)  9/20 (45.00%) 
Investigations     
Venous Pressure Jugular Increased  1  6/22 (27.27%)  4/20 (20.00%) 
Metabolism and nutrition disorders     
Fluid Overload, Dehydration  1  8/22 (36.36%)  4/20 (20.00%) 
Musculoskeletal and connective tissue disorders     
Muscle Spasms  1  6/22 (27.27%)  1/20 (5.00%) 
Nervous system disorders     
Dizziness, headache  1  10/22 (45.45%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal Pain  1  2/22 (9.09%)  6/20 (30.00%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sergey Sikora, President and CEO
Organization: CardioCell, LLC
Phone: 760-315-0861
EMail: SSIKORA@STEMCARDIOCELL.COM
Layout table for additonal information
Responsible Party: CardioCell LLC
ClinicalTrials.gov Identifier: NCT02467387    
Obsolete Identifiers: NCT02123706
Other Study ID Numbers: STEM-104-M-CHF
First Submitted: June 2, 2015
First Posted: June 10, 2015
Results First Submitted: October 25, 2019
Results First Posted: January 7, 2020
Last Update Posted: January 7, 2020