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 |
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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
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Hepatitis Hepatic Cirrhosis | Biological: Infusion of bone marrow mononuclear cells. | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Estimated 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 : | April 2015 |
| Estimated Primary Completion Date : | December 2018 |
| Estimated Study Completion Date : | June 2019 |
| 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. |
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02171949
| Contact: André C Lyra, PhD | 557132816455 | aclyra@live.com |
| Brazil | |
| Hospital São Rafael | Recruiting |
| Salvador, Bahia, Brazil, 41253-190 | |
| Contact: André C Lyra, PhD 55713281-6455 aclyra@live.com | |
| 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 |
| Responsible Party: | Ricardo Ribeiro dos Santos, PhD, Hospital Sao Rafael |
| ClinicalTrials.gov Identifier: | NCT02171949 History of Changes |
| Other Study ID Numbers: |
PCL 03/13 |
| First Posted: | June 24, 2014 Key Record Dates |
| Last Update Posted: | November 28, 2017 |
| Last Verified: | November 2017 |
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Chronic hepatitis Hepatic cirrhosis |
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Hepatitis Hepatitis, Chronic Liver Cirrhosis Liver Diseases |
Fibrosis Digestive System Diseases Pathologic Processes |