Liver DiseasePhase 1/2NCT00655707
A Phase I/II Safety and Tolerability Dose Escalation Study of Autologous Stem Cells to Patients With Liver Insufficiency
A Phase 1/2 study testing Autologous Expanded CD34+ Haemopoietic cells in people with Liver Disease, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This is a prospective dose escalation study of the administration of adult human stem cells in patients with end stage liver failure. Successive groups of two patients will receive ascending doses of autologous adult human stem cells starting at 1x10[9] cells. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Liver Disease
- What is being tested?
- Autologous Expanded CD34+ Haemopoietic cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2006to Apr 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged from 20 to 65 years of age
- Evidence of chronic liver insufficiency
- The presence of abnormal serum albumin and/or bilirubin and/or prothrombin time
- Patient is unlikely to receive a liver transplant
- Has a World Health Organisation (WHO) performance score of less than 2
- Has a life expectancy of at least 3 months
- Ability to give written consent
- Women of childbearing potential may be included, but must use a reliable and appropriate contraceptive method
Who cannot join
- Patients below the age of 20 or above the age of 65 years
- Pregnant or lactating women
- Patients with recent recurrent GI bleeding or spontaneous bacterial peritonitis
- Patients with evidence of HIV or other life threatening infection
- Patients unable to give written consent
- Patients with a history of hypersensitivity to Granulocyte-Colony Stimulating Factor (F-CSF)
- Patients who have been included in any other clinical trial within the previous month
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Safety and Tolerability Dose Escalation Study Following the Autologous Infusion of Expanded Adult Haematopoietic Stem Cells to Patients With Liver Insufficiency
This is a prospective dose escalation study of the administration of adult human stem cells in patients with end stage liver failure. Successive groups of two patients will receive ascending doses of autologous adult human stem cells starting at 1x10[9] cells. Following expansion in an approved Good Manufacturing Practice (GMP) facility the cells will be infused into either the hepatic artery or portal vein of research participants.
The aim of this trial is to determine the maximum tolerated dose of autologous adult stem cells when infused into either the hepatic artery or the portal vein. The maximum dose that would be given would be 5x10 to the ten [10].
To assess improvement in liver function as measured by serological and biochemical analysis and determine whether there are any symptomatic improvements as reported by the patients.
Read the detailed description
This is a prospective dose escalation study of the administration of expanded autologous adult human stem cells in patients with chronic liver insufficiency. Four groups of two patients will receive ascending doses of autologous adult human stem cells starting at a dose of 1 x 10[8] cells. The cells will be infused into either the hepatic artery or the portal vein of research participants. The consultant radiologist will review a duplex Doppler scan of the blood supply to the liver to determine the safest route for delivery of the cells.
The first patients (01 and 02) will receive 1 x 10[8] cells. If no adverse events are observed in either patient in the two-week period post stem cell administration, patient numbers 03 and 04 will receive 5 x 1[08] cells. This will continue through patients 05 and 06 receiving cells at 1 x 10[9] and 07 and 08 receiving 5 x 10[9] cells. If any patient in any cohort suffers adverse events considered to be treatment-related, the next group of patients will receive cells at a concentration one step down from that received by the patient suffering the adverse events.
At the completion of this first stage of the study, if no adverse treatment related events are seen, a further group of 10 patients will receive cells at a concentration of 5 x 10[9] cells.
It should be noted that if fewer cells are obtained at the end of the expansion period the re-infusion of the cells to the patient should nonetheless continue. This patient will be considered inevaluable and the next participant will be allocated their trial number.
The total period that each patient will be participating in the study is 12 weeks and the total duration of this clinical trial is expected to be approximately 12 months.
All patients will be assessed 4 weeks after coming off study (week 12), whether from completion of protocol or early withdrawal for whatever reason. They will also be monitored in the clinic for the remainder of their life.
Patients who are withdrawn due to issues of toxicity will be followed until the adverse event is resolved or the outcome is known. Patients will then be followed-up for four weeks after resolution and thereafter for life in the clinic.
- Conditions
- Liver Disease
- Being tested
- Autologous Expanded CD34+ Haemopoietic cells
- Keywords
- Adult stem cell therapy
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Expanded CD34+ Haemopoietic cellsBiological
Autologous expanded CD34+ cells obtained by leukapheresis on a single occasion by infusion into the hepatic artery or portal vein.
Patient numbers 01 and 02 will receive 1x109 cells Patient numbers 03 and 04 will receive 1x1010 cells Patient numbers 05 and 06 will receive 2x1010 cells Patient numbers 07 and 08 will receive 5x1010 cells
| Study group | Role | What they receive |
|---|---|---|
| Autologous CD34+ cells | Experimental | Autologous Cluster Designation 34+(CD34+) cells Receives: Biological: Autologous Expanded CD34+ Haemopoietic cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Tolerated the Maximum Dose
To determine the maximum tolerated dose of autologous adult stem cells when infused into either the hepatic artery or the portal vein.
Measured: 12 months
Number of Participants Without Specific Treatment Related Side Effect
To assess the safety of ascending doses of autologous adult stem cells when introduced into either the hepatic artery or the portal vein and to determine the maximum tolerated dose of stem cells.
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 posted10 Apr 2008 (estimated)
- Study startJan 2006
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nagy Habib, ChM FRCS, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00655707
- Sponsor's protocol ID
- HHSC/001
- Status last verified
- Oct 2019
- First submitted
- 4 Apr 2008
- Last updated
- 31 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Safety and Tolerability Dose Escalation Study Following the Autologous Infusion of Expanded Adult Haematopoietic Stem Cells to Patients With Liver Insufficiency
- ClinicalTrials.gov ID
- NCT00655707
- Acronym / sponsor ID
- HHSC/001
- Conditions
- Liver Disease
- Keywords
- Adult stem cell therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 10 Apr 2008 (estimated)
- Results
- Posted 31 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective dose escalation study of the administration of adult human stem cells in patients with end stage liver failure. Successive groups of two patients will receive ascending doses of autologous adult human stem cells starting at 1x10[9] cells. Following expansion in an approved Good Manufacturing Practice (GMP) facility the cells will be infused into either the hepatic artery or portal vein of research participants.
The aim of this trial is to determine the maximum tolerated dose of autologous adult stem cells when infused into either the hepatic artery or the portal vein. The maximum dose that would be given would be 5x10 to the ten [10].
To assess improvement in liver function as measured by serological and biochemical analysis and determine whether there are any symptomatic improvements as reported by the patients.
Detailed description
This is a prospective dose escalation study of the administration of expanded autologous adult human stem cells in patients with chronic liver insufficiency. Four groups of two patients will receive ascending doses of autologous adult human stem cells starting at a dose of 1 x 10[8] cells. The cells will be infused into either the hepatic artery or the portal vein of research participants. The consultant radiologist will review a duplex Doppler scan of the blood supply to the liver to determine the safest route for delivery of the cells.
The first patients (01 and 02) will receive 1 x 10[8] cells. If no adverse events are observed in either patient in the two-week period post stem cell administration, patient numbers 03 and 04 will receive 5 x 1[08] cells. This will continue through patients 05 and 06 receiving cells at 1 x 10[9] and 07 and 08 receiving 5 x 10[9] cells. If any patient in any cohort suffers adverse events considered to be treatment-related, the next group of patients will receive cells at a concentration one step down from that received by the patient suffering the adverse events.
At the completion of this first stage of the study, if no adverse treatment related events are seen, a further group of 10 patients will receive cells at a concentration of 5 x 10[9] cells.
It should be noted that if fewer cells are obtained at the end of the expansion period the re-infusion of the cells to the patient should nonetheless continue. This patient will be considered inevaluable and the next participant will be allocated their trial number.
The total period that each patient will be participating in the study is 12 weeks and the total duration of this clinical trial is expected to be approximately 12 months.
All patients will be assessed 4 weeks after coming off study (week 12), whether from completion of protocol or early withdrawal for whatever reason. They will also be monitored in the clinic for the remainder of their life.
Patients who are withdrawn due to issues of toxicity will be followed until the adverse event is resolved or the outcome is known. Patients will then be followed-up for four weeks after resolution and thereafter for life in the clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous CD34+ cells | Experimental | Biological: Autologous Expanded CD34+ Haemopoietic cellsAutologous Cluster Designation 34+(CD34+) cells |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients aged from 20 to 65 years of age
- Evidence of chronic liver insufficiency
- The presence of abnormal serum albumin and/or bilirubin and/or prothrombin time
- Patient is unlikely to receive a liver transplant
- Has a World Health Organisation (WHO) performance score of less than 2
Key exclusion criteria (7 listed)
- Patients below the age of 20 or above the age of 65 years
- Pregnant or lactating women
- Patients with recent recurrent GI bleeding or spontaneous bacterial peritonitis
- Patients with evidence of HIV or other life threatening infection
- Patients unable to give written consent
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 |
|---|---|---|
| Autologous Expanded CD34+ Haemopoietic cellsAutologous expanded CD34+ cells obtained by leukapheresis on a single occasion by infusion into the hepatic artery or portal vein. Patient numbers 01 and 02 will receive 1x109 cells Patient numbers 03 and 04 will receive 1x1010 cells Patient numbers 05 and 06 will receive 2x1010 cells Patient numbers 07 and 08 will receive 5x1010 cells | Biological | Autologous CD34+ cells |
Primary outcome
Number of Patients Who Tolerated the Maximum Dose
Time frame: 12 months
To determine the maximum tolerated dose of autologous adult stem cells when infused into either the hepatic artery or the portal vein.
Number of Participants Without Specific Treatment Related Side Effect
Time frame: 12 months
To assess the safety of ascending doses of autologous adult stem cells when introduced into either the hepatic artery or the portal vein and to determine the maximum tolerated dose of stem cells.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Nagy Habib, ChM FRCS principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous Expanded CD34+ Haemopoietic cells in people with Liver Disease, run by Imperial College London at 1 site in United Kingdom.
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 8 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: finished, as of the sponsor's last update on 31 Oct 2019. 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 United Kingdom. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 31 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Who Tolerated the Maximum Dose (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 31 Oct 2019; AzTrials last refreshed its copy on 30 Oct 2026.