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Clinical Trial for Evaluation of Treatment With Multiple Infusions of Mononuclear Bone Marrow Cells in Patients With Chronic Liver Diseases

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ClinicalTrials.gov Identifier: NCT02171949
Recruitment Status : Unknown
Verified November 2017 by Ricardo Ribeiro dos Santos, Hospital Sao Rafael.
Recruitment status was:  Recruiting
First Posted : June 24, 2014
Last Update Posted : November 28, 2017
Sponsor:
Collaborators:
Ministry of Science and Technology, Brazil
Ministry of Health, Brazil
Information provided by (Responsible Party):
Ricardo Ribeiro dos Santos, Hospital Sao Rafael

Tracking Information
First Submitted Date  ICMJE June 16, 2014
First Posted Date  ICMJE June 24, 2014
Last Update Posted Date November 28, 2017
Actual Study Start Date  ICMJE April 2015
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2014)
  • Evaluation of Child-Pugh score [ Time Frame: 12 months ]
    Functional class improvement of 2 points on Child-Pugh score.
  • Evaluation of MELD score [ Time Frame: 12 months ]
    Functional class improvement of 2 points on MELD score.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02171949 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2014)
  • Degree of muscle strength [ Time Frame: 12 months ]
    Improvement in the degree of muscle strength assessed using handgrip dynamometer.
  • Hepatic fibrosis [ Time Frame: 12 months ]
    Decrease of hepatic fibrosis detected by elastography shear waves.
  • Quality of life [ Time Frame: 12 months ]
    Improvement on the SF-36 questionnaire score, which evaluates quality of life.
  • Evaluation of functional capacity [ Time Frame: 12 months ]
    Improvement in the functional capacity, assessed by six-minute walk test.
  • Evaluation of serum bilirubin levels [ Time Frame: 12 months ]
    Improvement in the serum bilirubin levels.
  • Evaluation of serum albumin levels [ Time Frame: 12 months ]
    Improvement in the serum albumin levels.
  • Evaluation of prothrombin time [ Time Frame: 12 months ]
    Improvement in prothrombin time.
  • Evaluation of serum levels of cytokines [ Time Frame: 12 months ]
    Decrease in the serum levels of cytokines.
  • Evaluation of fibrosis markers levels [ Time Frame: 12 months ]
    Decrease in the serum levels of fibrosis markers.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial for Evaluation of Treatment With Multiple Infusions of Mononuclear Bone Marrow Cells in Patients With Chronic Liver Diseases
Official Title  ICMJE Randomized, Open and Controlled Clinical Trial for Evaluation of Treatment With Multiple Infusions of Mononuclear Bone Marrow Cells in Patients With Chronic Liver Diseases
Brief Summary The purpose of this study is to evaluate the safety and efficacy of multiple infusions of mononuclear bone marrow cells in patients with chronic liver diseases.
Detailed Description

This is a safety/efficacy phase II, open, randomized, controlled clinical trial, with two arms. The study population will consist of 30 patients with chronic decompensated liver disease (Child-Pugh B or C). The candidates included in the study will be asked to voluntarily participate and sign the written consent.

The patients will be allocated randomly into 2 groups: in group A, the patients will undergo the intervention; and in group B, the patients will be the controls. Patients of both groups will receive clinical follow-up. They will be maintained on drug therapy commonly used in patients with cirrhosis, which may include: spironolactone, furosemide, lactulose, metronidazole, neomycin, analogs of nucleoside / nucleotide in patients with hepatitis B, and vitamin complexes.

All patients included in Group A will undergo cell therapy according to the technique described as follows: on day 1 (D-1), patients will be hospitalized to undergo the bone marrow puncture through the iliac crest. 150 to 200 ml of bone marrow aspirate will be collected. The procedure will be done under local anesthesia and sedation. The fraction of mononuclear cells will be isolated from the aspirated marrow by the SEPAX (System of cell processing) - Biosafe, Switzerland.

The enriched fraction of collected mononuclear cells will be resuspended in saline. The obtained cell populations will be analyzed by flow cytometry for its characterization, and then diluted in 20 ml saline. The cells will be injected 3 times throughout the study, on days 1 (D-1), 30 (D-30) and 60 (D-60).

Patients will undergo a series of clinical and laboratory evaluations and will also be submitted to the following procedures:

  • Cell blood count
  • Biochemical analysis (measurement of electrolytes - sodium and potassium)
  • Renal function tests (urea and creatinine)
  • Liver profile tests (total proteins and fractions, bilirubin, prothrombin time, transaminases, alkaline phosphatase, gamma-GT)
  • Metabolic profile (glucose, total cholesterol and fractions, triglycerides)
  • Thyroid profile tests
  • Serology required for blood transfusion and bone marrow transplant in Brazil
  • Alpha-fetoprotein
  • Beta-HCG (human chorionic gonadotropin), for women
  • Handgrip dynamometer
  • Treadmill test
  • Six-minute walk test
  • Abdomen doppler ultrasound
  • Magnetic resonance imaging of the upper abdomen with elastography
  • Measurement of serum factors
  • Shear wave elastography

Also, the patients will respond to questions from the SF (Short Form) -36 questionnaire (for assessment of quality of life).

Clinical follow-up will be kept for patients who suspend their participation in the study for any adverse event and / or laboratory abnormality, or for the patient's own desire, following insurance protocols. In addition to the clinical and surgical follow-up, specific medical care will be offered to patients who experience adverse events, until stabilization of the patient, even if the target date for completion of the study has been exceeded.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Hepatitis
  • Hepatic Cirrhosis
Intervention  ICMJE Biological: Infusion of bone marrow mononuclear cells.
Patients on this group will receive therapy with mononuclear cells. The cells will be diluted on saline and then injected on the hepatic artery through femoral artery puncture.
Study Arms  ICMJE
  • No Intervention: Control group
  • Active Comparator: Bone marrow mononuclear cell therapy
    Intervention: Biological: Infusion of bone marrow mononuclear cells.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 20, 2014)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2019
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of liver cirrhosis of different etiologies, confirmed by clinical examination, laboratory tests, imaging studies and / or biopsy that shows process of evolution to cirrhosis or established cirrhosis (equivalent to Metavir score F3/F4);
  • Non-participation on the waiting list for liver transplantation or, in case of participation, allocation after the fifth position in the list, for subjects with blood group A or O, and after the third position for subjects with other blood groups;
  • Absence of clinical, laboratory and radiological evidence of hepatocellular carcinoma;
  • Absence of pregnancy potential or negative pregnancy test for female patients, or impossibility to use a contraception method during the study;
  • Permission for doing the puncture of iliac crest after evaluation of pre-anesthetic visit.

Exclusion Criteria:

  • Impossibility to obtain vascular access for percutaneous procedure;
  • Sepsis;
  • Hepatic encephalopathy detected at the screening tests;
  • Budd-Chiari syndrome;
  • Severe coagulopathy with INR > 2,4 or platelet count < 30.000;
  • Presence of malignancies (excluding non-melanoma skin cancer);
  • Decompensated heart failure;
  • Primary hematologic diseases;
  • Renal failure with creatinin > 2,5mg/dl;
  • Coinfection with HIV;
  • Pregnancy;
  • Dependence of organic medium such as circulatory or ventilatory;
  • Any other comorbidity with an impact on the survival in 2 years;
  • Participation in other clinical trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02171949
Other Study ID Numbers  ICMJE PCL 03/13
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ricardo Ribeiro dos Santos, Hospital Sao Rafael
Study Sponsor  ICMJE Hospital Sao Rafael
Collaborators  ICMJE
  • Ministry of Science and Technology, Brazil
  • Ministry of Health, Brazil
Investigators  ICMJE
Principal Investigator: André C Lyra, PhD Hospital São Rafael
Study Chair: Bruno SF Souza, MD, Msc Hospital São Rafael
Study Chair: Eduardo L Braga, PhD Hospital São Rafael
Study Chair: Lourianne N Cavalcante, PhD Hospital São Rafael
Study Chair: Milena BP Soares, PhD Hospital São Rafael
Principal Investigator: Ricardo R dos Santos, PhD Hospital São Rafael
Study Chair: Ticiana F Larocca, MD, Msc Hospital São Rafael
PRS Account Hospital Sao Rafael
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP