AzTrials
AzTrials

End Stage Liver DiseasePhase 3NCT03109236

Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis

A Phase 3 study testing GCSF and CD133 Cells Transplantation in people with End Stage Liver Disease, run by National University Hospital, Singapore at 1 site in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis. Read more about this study

Who is it for?
Ages 21 to 70 years
Conditions the study is for
End Stage Liver Disease
What is being tested?
GCSF and CD133 Cells Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteSingapore
Study dates
24 Aug 2017to 31 Dec 2023
Phase
Phase 3
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 21 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Liver cirrhosis of any aetiology but where active disease is controlled
  • Childs A/B/C with Child-Pugh score >= 5
  • And either one of the following:
  • MELD score 10-27
  • Clinically significant portal hypertension as evidenced by gastroesophageal varices or ascites

Who cannot join

  • MELD score >27
  • INR>2.5
  • HIV
  • History of hematological or hepatic malignancy within 5 years from consent
  • Other underlying malignancy with <1 year survival
  • Presence of systemic diseases that may impact survival within 1 year.
  • Listed for liver transplant

Trial locations and contacts

1 site in 1 country.

Nur Halisah contact

66015193

mdcnhj@nus.edu.sg

Dan Yock Young contact

67727641

yock_young_dan@nuhs.edu.sg

Singapore1 site, 1 recruiting

  • National University Hospital

    Singapore, 119074

    Dan Yock Young

    Mark Muthiah

    Recruiting

Other trials in Singapore

About this study

This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis.

Read the detailed description

This is a 2 arm randomised study patients with decompensated liver cirrhosis involving minimum of 23 and maximum of 33 patients in each arm.

The investigators propose that transplantation of mobilized autologous CD133+ cells harvested from the bone marrow directly into the liver has the ability to replace and regenerate the damaged sinusoidal endothelium as well as normalize macrophage and Natural Killer (NK) cell function. The niche provided by the refenestrated endothelium can polarize the macrophage to antifibrotic phenotype as well as directly inactivate the activated myofibroblast, resulting in reversal of liver fibrosis and improvement in liver function. Transplantation of cells will be via intraportal route delivered by percutaneous cannulation of the portal vein system.

Being tested
GCSF, CD133 Cells Transplantation
Medical subject headings
End Stage Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GCSFDrug

    5 doses of GCSF injection will be injected under the skin on the abdomen to mobilize the bone marrow cells.

  • CD133 Cells TransplantationProcedure or surgery

    Also called Endothelial Progenitor cells

    Endothelial progenitor cells are harvested by CD133+ MACS (magnetic activated cell sorting) sort selection of bone marrow and a minimum of 1x 10^6 and up to 50-100 x 10^6 cells are transplanted to one lobe of the liver via a percutaneous catheter inserted into the portal venous system by percutaneous transhepatic approach for engraftment.

Study groups in NCT03109236
Study groupRoleWhat they receive
TreatmentExperimentalPatient will undergo CD133+ cells transplantation at stable compensated state. 5 dose GCSF will be administered 5 days consecutively before bone marrow harvesting. Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system. Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins.
Receives: Drug: GCSF; Procedure: CD133 Cells Transplantation
ControlActive comparatorNon-Transplant Arm: Patients will receive 5 doses of GCSF
Receives: Drug: GCSF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Improvement of Fibrosis Staging (Ishak)

    Improvement of Fibrosis Staging (Ishak) > 1 point

    Measured: 3 months

  2. Improvement of liver fibrosis on MRE (magnetic resonance elastography)

    Improvement of liver fibrosis on MRE (magnetic resonance elastography) > 2 point

    Measured: 6 months

  3. Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State

    Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State by at least 2 points

    Measured: 6 months

  4. Improvement of quantitative fibrosis

    Improvement of quantitative fibrosis on histology > 10%

    Measured: 1 year

Secondary outcomes (6)

  1. Overall Survival and Improvement

    Overall Survival

    Measured: 1 year

  2. Overall Improvement in Liver Function Tests

    Improvement in Liver Function Tests, especially Total Bilirubin, Albumin and Prothrombin Time

    Measured: 1 year

  3. Improvement of Hepatic Venous Pressure

    Improvement of Hepatic Venous Pressure

    Measured: 3 months

  4. Incidence of clinical decompensation

    Frequency of Incidence of clinical decompensation

    Measured: 1 year

  5. Overall Improvement of Patient Reported outcome

    Improvement of Patient Reported outcome (quality of life Short Form Health Survey SF-36 for liver cirrhosis)

    Measured: 6 months

  6. Overall Improvement of MELD score

    Rate of deterioration of MELD score (Kaplan Meier analysis)

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2017
  2. Study start24 Aug 2017
  3. Primary completion31 Dec 2022 (estimated)
  4. Study completion31 Dec 2023 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a 2 arm randomised study patients with decompensated liver cirrhosis involving 33 patients in each arm. Randomisation will be done by statistician to determine which arm patients will be in (control / treatment). Treatment arm: Patient will undergo CD133+ cells transplantation at stable compensated state. 5 dose Granulocyte Colony Stimulating Factor (GCSF) will be administered 5 days consecutively before bone marrow harvesting. Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins. Control Arm: Patients will receive 5 doses of GCSF
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03109236
Sponsor's protocol ID
2016/00711
Other IDs
2016
Status last verified
Jan 2021
First submitted
6 Mar 2017
Last updated
19 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GCSF and CD133 Cells Transplantation in people with End Stage Liver Disease, run by National University Hospital, Singapore at 1 site in Singapore.

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 7 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 19 Jan 2021. 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 Singapore. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Nur Halisah (66015193, mdcnhj@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement of Fibrosis Staging (Ishak) (time frame: 3 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03109236.

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 19 Jan 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in