Condition category
Nutritional, Metabolic, Endocrine
Date applied
29/02/2008
Date assigned
10/03/2008
Last edited
05/07/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Laurent Spahr

ORCID ID

Contact details

University Hospital of Geneva
24
Rue Micheli-du-Crest
Geneva
CH-1211
Switzerland
+41 22 372 93 40
Laurent.Spahr@hcuge.ch

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Swissmedic 2008DR2031

Study information

Scientific title

Autologous human bone marrow stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) to improve liver function in patients with decompensated alcoholic liver disease: a randomized study

Acronym

Study hypothesis

Patients with advanced alcoholic liver disease often come to medical attention due to hepatic decompensation (fatigue, jaundice, ascites, bleeding and hepatic encephalopathy). The prognosis depends on the severity of the liver insufficiency. The characteristic features of patients who do not survive is profound liver failure and inability to achieve efficient parenchymal regeneration.

Study hypothesis:
The combination of stimulating autologous hematopoietic stem cells from the bone marrow after a 5-day mobilization course with G-CSF followed by a direct administration into the liver parenchyma via the hepatic artery translates into a better outcome during follow-up as compared to the standard care (which included only supportive measures).

Please note that as of 04/01/10 the anticipated end date for this trial has been extended from 31/03/10 to 31/12/10.

Ethics approval

Protocol N°07-145 approved by the local Ethics Committee (Comite Departemental D'Ethique de Médecine Interne et Médecine Communautaire, 24, Rue Micheli-du-Crest CH-1211 Geneve Switzerland) on November 6, 2007. Also approved by the national Swiss Agency for Therapeutic Products (2008DR2031) on February 7, 2008.

Study design

Single-center randomized controlled study, not blinded.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Alcoholic liver disease

Intervention

The participants will be randomly allocated to the two study arms in equal numbers by an independent person using the sealed envelope technique.

Intervention arm: Stem cell embolisation in the hepatic artery
Control arm: supportive measures only

The following tests will be carried out in both arms at baseline:
1. Liver biopsy
2. Computed tomography (CT) with volumetry
3. Physical examination
4. Blood sampling for cytokines (tumor necrosis factor [TNF], Interleukin-6 [IL6], alpha-fetoprotein [AFP], Hepatocyte Growth Factor [HGF], transforming growth factor [TGF]-beta)
5. Routine hematology and coagulation studies
6. Blood chemistry with liver function test (to measure the MELD score)

Control arm: Supportive measures according to the standard care.
The following will be carried out at Day 28 visit:
1. Repeat liver biopsy
2. Physical examination
3. CT with volumetry
4. Blood sampling (idem)

Day 60 and day 90 visits will include only physical examination and blood tests.

In the treatment arm: Five-day mobilization course with lenograstim (G-CSF) 10 mcg/kg subcutaneously per day, followed by a 40 to 60 ml bone marrow aspiration from the iliac crest. Then, CD34+ and mesenchymal cells will be isolated from the aspirate using a classical Ficoll density separation. Within 36 h of aspiration, the suspension of cells (an average of 0.5 x 10^8 cells) will be selectively embolized via arteriography into the right and left hepatic artery branches, so as to distribute CD34+ and mesenchymal cells in both lobes of the liver. Day 28, 60 and 90 visits will be similar to the control arm.

Intervention type

Drug

Phase

Not Specified

Drug names

granulocyte colony-stimulating factor (G-CSF)

Primary outcome measures

Improvement of liver function, as assessed by a decrease in the MELD score of >3 between baseline, Day 28, 60, and 90 follow-up visits.

Secondary outcome measures

1. Improvement in liver function as assessed by the following parameters at Day 28, 60, and 90:
1.1. Bilirubin
1.2. Albumin
1.3. Coagulation times
1.4. Presence or absence of ascites
1.5. Presence or absence of hepatic encephalopathy)
This will allow the calculation of the Child-Pugh's score
2. Mortality at 3 and 6 months
3. Evolution of serum markers of liver regeneration (AFP, HGF), inflammation (TNF, IL6) and fibrosis (TGF-beta)
4. Changes in liver histology at Day 28

Overall trial start date

01/03/2008

Overall trial end date

31/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 18-75 years
2. Biopsy-proven alcoholic liver disease
3. Abnormal liver function with a Model for End-Stage Liver Disease (MELD) (assessment that include bilirubin, coagulation time and creatinine) score 10-26
4. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. Recent (10 days) infection or hemorrhage
2. Estimated survival <6 months
3. Coexistent HIV, hepatitis C virus (HCV), hepatitis B virus (HBV)
4. Portal vein obstruction
5. Documented hepatocellular carcinoma
6. Severe liver atrophy as defined by volumetry <0.6% body weight
7. Leucocytes >25g/L
8. Known hypersensitivity to G-CSF
9. Creatinine >150 µmol/L
10. Contraindication to arteriography
11. Clinically overt hepatic encephalopathy
12. Absence of written consent

Recruitment start date

01/03/2008

Recruitment end date

31/12/2010

Locations

Countries of recruitment

Switzerland

Trial participating centre

University Hospital of Geneva
Geneva
CH-1211
Switzerland

Sponsor information

Organisation

Foundation for Liver and Gut Studies (FLAGS) (Switzerland)

Sponsor details

12
Rue Adrien Lachenal
Geneva
CH-1207
Switzerland

Sponsor type

Other

Website

Funders

Funder type

Other

Funder name

Foundation for Liver and Gut Studies (FLAGS), a non profit organisation based in Geneva (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University Hospital of Geneva (Hôpitaux Universaires de Genève; HUG) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23341981

Publication citations

  1. Results

    Spahr L, Chalandon Y, Terraz S, Kindler V, Rubbia-Brandt L, Frossard JL, Breguet R, Lanthier N, Farina A, Passweg J, Becker CD, Hadengue A, Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial., PLoS ONE, 2013, 8, 1, e53719, doi: 10.1371/journal.pone.0053719.

Additional files

Editorial Notes