Chronic HepatitisPhase 2NCT02171949
Clinical Trial for Evaluation of Treatment With Multiple Infusions of Mononuclear Bone Marrow Cells in Patients With Chronic Liver Diseases
A Phase 2 study testing Infusion of bone marrow mononuclear cells. in people with Chronic Hepatitis and Hepatic Cirrhosis, run by Hospital Sao Rafael at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis, Hepatic Cirrhosis
- What is being tested?
- Infusion of bone marrow mononuclear cells.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- Apr 2015to Jun 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital São Rafael
Salvador, Estado de Bahia, 41253-190
André C Lyra, PhD, 55713281-6455, aclyra@live.com
About this study
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
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.
Read the 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.
- Conditions
- Chronic Hepatitis, Hepatic Cirrhosis
- Being tested
- Infusion of bone marrow mononuclear cells.
- Keywords
- Chronic hepatitis, Hepatic cirrhosis
- Medical subject headings
- Hepatitis, Chronic, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of bone marrow mononuclear cells.Biological
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 group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Not described |
| Bone marrow mononuclear cell therapy | Active comparator | Not described Receives: Biological: Infusion of bone marrow mononuclear cells. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Child-Pugh score
Functional class improvement of 2 points on Child-Pugh score.
Measured: 12 months
Evaluation of MELD score
Functional class improvement of 2 points on MELD score.
Measured: 12 months
Secondary outcomes (9)
Degree of muscle strength
Improvement in the degree of muscle strength assessed using handgrip dynamometer.
Measured: 12 months
Hepatic fibrosis
Decrease of hepatic fibrosis detected by elastography shear waves.
Measured: 12 months
Quality of life
Improvement on the SF-36 questionnaire score, which evaluates quality of life.
Measured: 12 months
Evaluation of functional capacity
Improvement in the functional capacity, assessed by six-minute walk test.
Measured: 12 months
Evaluation of serum bilirubin levels
Improvement in the serum bilirubin levels.
Measured: 12 months
Evaluation of serum albumin levels
Improvement in the serum albumin levels.
Measured: 12 months
Evaluation of prothrombin time
Improvement in prothrombin time.
Measured: 12 months
Evaluation of serum levels of cytokines
Decrease in the serum levels of cytokines.
Measured: 12 months
Evaluation of fibrosis markers levels
Decrease in the serum levels of fibrosis markers.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2014 (estimated)
- Study startApr 2015
- Primary completionDec 2018 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Sao Rafael
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Brazil, Ministry of Health, Brazil
- Responsible party
- Principal investigator, Ricardo Ribeiro dos Santos, Hospital Sao Rafael
- Investigators
- André C Lyra, PhD, Principal investigator, Hospital São RafaelBruno SF Souza, MD, Msc, Study chair, Hospital São RafaelEduardo L Braga, PhD, Study chair, Hospital São RafaelLourianne N Cavalcante, PhD, Study chair, Hospital São RafaelMilena BP Soares, PhD, Study chair, Hospital São RafaelRicardo R dos Santos, PhD, Principal investigator, Hospital São RafaelTiciana F Larocca, MD, Msc, Study chair, Hospital São Rafael
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02171949
- Sponsor's protocol ID
- PCL 03/13
- Status last verified
- Nov 2017
- First submitted
- 16 Jun 2014
- Last updated
- 28 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02171949
- Acronym / sponsor ID
- PCL 03/13
- Conditions
- Chronic Hepatitis, Hepatic Cirrhosis
- Keywords
- Chronic hepatitis, Hepatic cirrhosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hospital Sao RafaelUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Brazil, Ministry of Health, Brazil
- Study start
- Apr 2015 (actual)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 24 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | – |
| Bone marrow mononuclear cell therapy | Active comparator | Biological: Infusion of bone marrow mononuclear cells. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Biological | Bone marrow mononuclear cell therapy |
Primary outcome
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.
9 secondary outcomes
Degree of muscle strength
Time frame: 12 months
Hepatic fibrosis
Time frame: 12 months
Quality of life
Time frame: 12 months
Evaluation of functional capacity
Time frame: 12 months
Evaluation of serum bilirubin levels
Time frame: 12 months
Evaluation of serum albumin levels
Time frame: 12 months
Evaluation of prothrombin time
Time frame: 12 months
Evaluation of serum levels of cytokines
Time frame: 12 months
Evaluation of fibrosis markers levels
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
André C Lyra, PhD principal investigator
Hospital São Rafael
Bruno SF Souza, MD, Msc study chair
Hospital São Rafael
Eduardo L Braga, PhD study chair
Hospital São Rafael
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Infusion of bone marrow mononuclear cells. in people with Chronic Hepatitis and Hepatic Cirrhosis, run by Hospital Sao Rafael at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact André C Lyra, PhD (557132816455, aclyra@live.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Child-Pugh score (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2017.