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

Brief Title

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

Official Title

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Evaluation of Child-Pugh score

Secondary Outcome

 Degree of muscle strength

Condition

Chronic Hepatitis

Intervention

Infusion of bone marrow mononuclear cells.

Study Arms / Comparison Groups

 Control group
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

30

Start Date

April 2015

Completion Date

June 2019

Primary Completion Date

December 2018

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

André C Lyra, PhD, 557132816455, [email protected]

Location Countries

Brazil

Location Countries

Brazil

Administrative Informations


NCT ID

NCT02171949

Organization ID

PCL 03/13


Responsible Party

Principal Investigator

Study Sponsor

Hospital Sao Rafael

Collaborators

 Ministry of Science and Technology, Brazil

Study Sponsor

André C Lyra, PhD, Principal Investigator, Hospital São Rafael


Verification Date

November 2017