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

Sponsor

Hospital Sao Rafael (Other)

Overall Status

Unknown status

CT.gov ID

NCT02171949

Collaborator

Ministry of Science and Technology, Brazil (Other), Ministry of Health, Brazil (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis Hepatic Cirrhosis	Biological: Infusion of bone marrow mononuclear cells.	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control group
Active Comparator: Bone marrow mononuclear cell therapy	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.

Arm

Intervention/Treatment

No Intervention: Control group

Active Comparator: Bone marrow mononuclear cell therapy

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.

Outcome Measures

Primary Outcome Measures

Evaluation of Child-Pugh score [12 months]
Functional class improvement of 2 points on Child-Pugh score.
Evaluation of MELD score [12 months]
Functional class improvement of 2 points on MELD score.

Secondary Outcome Measures

Degree of muscle strength [12 months]
Improvement in the degree of muscle strength assessed using handgrip dynamometer.
Hepatic fibrosis [12 months]
Decrease of hepatic fibrosis detected by elastography shear waves.
Quality of life [12 months]
Improvement on the SF-36 questionnaire score, which evaluates quality of life.
Evaluation of functional capacity [12 months]
Improvement in the functional capacity, assessed by six-minute walk test.
Evaluation of serum bilirubin levels [12 months]
Improvement in the serum bilirubin levels.
Evaluation of serum albumin levels [12 months]
Improvement in the serum albumin levels.
Evaluation of prothrombin time [12 months]
Improvement in prothrombin time.
Evaluation of serum levels of cytokines [12 months]
Decrease in the serum levels of cytokines.
Evaluation of fibrosis markers levels [12 months]
Decrease in the serum levels of fibrosis markers.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.