Hepatorenal SyndromeNCT00734136
Role Of Angiogenic Factors In The Development Of Hepatorenal Syndrome
A study testing Blood Draws and a hepatectomy specimen in people with Hepatorenal Syndrome and Renal Failure, run by Lahey Clinic at 1 site in United States.
Trial summary
This Study will look at the effect of substances called "angiogenic factors"(development of new blood vessels) have on the development of severe liver disease. The results may help to understand the factors involved in the repair and regeneration of liver tissue and to see if different types of liver disease are… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatorenal Syndrome, Renal Failure, Liver Diseases
- What is being tested?
- Blood Draws and a hepatectomy specimen
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Feb 2009
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sign informed consent
- Subjects who present for Liver Transplantation
- Subjects who present for Hepatic resection
- Subjects with Non-Surgical Liver Disease
Who cannot join
- Absence of Liver Disease
Trial locations and contacts
1 site in 1 country.
About this study
This Study will look at the effect of substances called "angiogenic factors"(development of new blood vessels) have on the development of severe liver disease. The results may help to understand the factors involved in the repair and regeneration of liver tissue and to see if different types of liver disease are associated with different types of factors, especially in the severe liver disease called hepatorenal syndrome.
Read the detailed description
Renal dysfunction in patients who also suffer from end stage liver disease is associated with increased morbidity and mortality comparted to patients suffering from liver disease alone. If frank renal failure develops in a patient with cirrhosis and ascites, the median survival time from onset of renal failure is approximately 2 weeks. Kidney dysfunction may be transient, secondary to pooling of blood in the splanchnic bed and consequent reduction in renal blood flow. In this instance, liver transplantation and restoration of normal circulatory patterns will result in return of normal renal function.
Currently, there is no diagnostic test to differentiate between temporary and permanent renal dysfunction in the presence of end stage liver disease. As a result, the number of combined liver-kidney transplant occuring has steadily increased. Slightly more than 20%(8 of 38) of the liver transplants performed by our service in 2004 have been combined liver-kidney transplants. The double procedure increases the length of anesthesia exposure and surgical time, and the presence of the transplanted kidney may require increased immunosuppression in comparison to a liver-only transplant.
We plan to examine the role of angiogenic factors in the abnormal blood flow patterns known to be associated with hepatorenal syndrome.
Specimen analysis: Circulating levels of cytokines and growth factors will be measured using commercially available ELISAs. Matrix metalloproteins will be measured by quantitative electrophoresis.
Expression of A20 will be determined by extraction of total RNA from whole blood using Trizol and run in standard Northern blot methodology. RNA will by hybridized with [³²P]-dATP labeled A20 probes and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) or β-actin probes to correct for uneven loading. Similar RNA extraction will be performed on liver tissue obtained at time of surgery. Microarray analysis will be performed on the extract to identify specific genes that may be involved in the pathogenesis of HRS.
Results of laboratory analyses will be correlated with clinical parameters and attempts will be made to identify specific cytokines or up-regulated genes with particular phases or degree or renal dysfunction in patients with liver disease. Similar analyses will be performed in patients with other types of hepatic disease.
- Conditions
- Hepatorenal Syndrome, Renal Failure, Liver Diseases
- Being tested
- Blood Draws and a hepatectomy specimen, Blood draw - pre operative standard of care
- Keywords
- Angiogenic Factors, Hepatorenal Syndrome, Liver Disease, Renal Failure, Liver Cirrhosis, Ascites
- Medical subject headings
- Hepatorenal Syndrome, Renal Insufficiency, Liver Diseases, Liver Cirrhosis, Ascites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood Draws and a hepatectomy specimenProcedure or surgery
Pre operative blood draw(1.5 ml serum, 1.5 ml EDTA)(approximately 2 teaspoons).
Blood draw during surgery(1.5 ml serum, 1.5 ml EDTA)from Hepatic Artery, Hepatic Vein, and Portal Vein.
Wedge section of Hepatectomy specimen following resection in surgical subjects(tested for the same factors)
Blood draw - pre operative standard of careProcedure or surgery
Pre-operative blood draw(1.5 ml serum, 1.5 ml EDTA)(approximately 2 teaspoons) from peripheral vein
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | 50 surgical subjects undergoing either liver transplantation or hepatic resection Receives: Procedure: Blood Draws and a hepatectomy specimen |
| 2 | Other | 50 Subjects with Liver disease who are are not surgical candidates Receives: Procedure: Blood draw - pre operative standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of Blood samples for angiogenic factors
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startMay 2005
- Primary completionJul 2005
- Study completionFeb 2009
Why it stopped: Insufficient findings for data analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatorenal SyndromeStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lahey Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Dr. Vikas Sukhatme
- Investigators
- Mary Ann Simpson, Ph.D., Principal investigator, Lahey Clinic, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734136
- Sponsor's protocol ID
- 2005-040
- Status last verified
- Feb 2009
- First submitted
- 12 Aug 2008
- Last updated
- 18 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004 Feb 12;350(7):672-83. doi: 10.1056/NEJMoa031884. Epub 2004 Feb 5.
PubMed 14764923
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role Of Angiogenic Factors In The Development Of Hepatorenal Syndrome
- ClinicalTrials.gov ID
- NCT00734136
- Acronym / sponsor ID
- 2005-040
- Conditions
- Hepatorenal Syndrome, Renal Failure, Liver Diseases
- Keywords
- Angiogenic Factors, Hepatorenal Syndrome, Liver Disease, Renal Failure, Liver Cirrhosis, Ascites
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient findings for data analysis
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Lahey ClinicUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Dr. Vikas Sukhatme
- Study start
- May 2005
- Primary completion
- Jul 2005 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 14 Aug 2008 (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.
This Study will look at the effect of substances called "angiogenic factors"(development of new blood vessels) have on the development of severe liver disease. The results may help to understand the factors involved in the repair and regeneration of liver tissue and to see if different types of liver disease are associated with different types of factors, especially in the severe liver disease called hepatorenal syndrome.
Detailed description
Renal dysfunction in patients who also suffer from end stage liver disease is associated with increased morbidity and mortality comparted to patients suffering from liver disease alone. If frank renal failure develops in a patient with cirrhosis and ascites, the median survival time from onset of renal failure is approximately 2 weeks. Kidney dysfunction may be transient, secondary to pooling of blood in the splanchnic bed and consequent reduction in renal blood flow. In this instance, liver transplantation and restoration of normal circulatory patterns will result in return of normal renal function.
Currently, there is no diagnostic test to differentiate between temporary and permanent renal dysfunction in the presence of end stage liver disease. As a result, the number of combined liver-kidney transplant occuring has steadily increased. Slightly more than 20%(8 of 38) of the liver transplants performed by our service in 2004 have been combined liver-kidney transplants. The double procedure increases the length of anesthesia exposure and surgical time, and the presence of the transplanted kidney may require increased immunosuppression in comparison to a liver-only transplant.
We plan to examine the role of angiogenic factors in the abnormal blood flow patterns known to be associated with hepatorenal syndrome.
Specimen analysis: Circulating levels of cytokines and growth factors will be measured using commercially available ELISAs. Matrix metalloproteins will be measured by quantitative electrophoresis.
Expression of A20 will be determined by extraction of total RNA from whole blood using Trizol and run in standard Northern blot methodology. RNA will by hybridized with [³²P]-dATP labeled A20 probes and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) or β-actin probes to correct for uneven loading. Similar RNA extraction will be performed on liver tissue obtained at time of surgery. Microarray analysis will be performed on the extract to identify specific genes that may be involved in the pathogenesis of HRS.
Results of laboratory analyses will be correlated with clinical parameters and attempts will be made to identify specific cytokines or up-regulated genes with particular phases or degree or renal dysfunction in patients with liver disease. Similar analyses will be performed in patients with other types of hepatic disease.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Procedure: Blood Draws and a hepatectomy specimen50 surgical subjects undergoing either liver transplantation or hepatic resection |
| 2 | Other | Procedure: Blood draw - pre operative standard of care50 Subjects with Liver disease who are are not surgical candidates |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Sign informed consent
- Subjects who present for Liver Transplantation
- Subjects who present for Hepatic resection
- Subjects with Non-Surgical Liver Disease
Key exclusion criteria (1 listed)
- Absence of Liver Disease
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 |
|---|---|---|
| Blood Draws and a hepatectomy specimenPre operative blood draw(1.5 ml serum, 1.5 ml EDTA)(approximately 2 teaspoons). Blood draw during surgery(1.5 ml serum, 1.5 ml EDTA)from Hepatic Artery, Hepatic Vein, and Portal Vein. Wedge section of Hepatectomy specimen following resection in surgical subjects(tested for the same factors) | Procedure or surgery | 1 |
| Blood draw - pre operative standard of carePre-operative blood draw(1.5 ml serum, 1.5 ml EDTA)(approximately 2 teaspoons) from peripheral vein | Procedure or surgery | 2 |
Primary outcome
Analysis of Blood samples for angiogenic factors
Time frame: 1 week
Results and safety
The study was stopped early (reason given: Insufficient findings for data analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2009.
- Background: PubMed 14764923Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004 Feb 12;350(7):672-83. doi: 10.1056/NEJMoa031884. Epub 2004 Feb 5.
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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.
Mary Ann Simpson, Ph.D. principal investigator
Lahey Clinic, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood Draws and a hepatectomy specimen in people with Hepatorenal Syndrome and Renal Failure, run by Lahey Clinic at 1 site in United States.
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 4 inclusion and 1 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: stopped early, as of the sponsor's last update on 18 Feb 2009. 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 States. 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.
Are results available for this study?
The study was stopped early (reason given: Insufficient findings for data analysis). Results are not available in the source record.
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?
Analysis of Blood samples for angiogenic factors (time frame: 1 week). 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 NCT00734136, which also lists 1 linked publication.
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 18 Feb 2009.