Hepatitis CPhase 2NCT00324389
Interferon-Induced Gene Expression in Liver Cells and Peripheral Blood Lymphocytes
A Phase 2 study testing Interferon alpha in people with Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This proposal seeks to use DNA analyses to understand how racial and genetic factors influence interferon (treatment) response in HCV infection in African Americans. A better understanding should allow rational design of new therapies or better use of existing therapies. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Interferon alpha
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Jun 2006
- 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 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male non-Hispanic African-American or non-Hispanic Caucasian patients between 18 and 65 years of age
- Abstinence from any ingestion of alcohol and smoking for at least 7 days prior to study for those who drink or smoke socially
- HCV genotype 1 (1a, 1b or mixture of 1a and 1b). HCV genotyping will be performed at the Molecular Diagnostic Laboratory at UTMB using the LiPA assay (Innogenetics)
- Presence of HCV RNA in serum (>10 [to the fifth power] copies/ml)
- Not previously treated with any interferon and/ or ribavirin
- Compensated liver disease with the following laboratory criteria:
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- Hemoglobin greater than or equal to 13 gm/dl for males
- Granulocyte count greater than or equal to 1,000/cubic mm
- Platelets greater than or equal to 100,000/cubic mm
- Prothrombin time <2 sec. elevation
- Total bilirubin (0.1-1.1 mg/dl). If elevated, the conjugated Bilirubin must be within normal limits (0-0.3 mg/dl)
- Serum albumin within normal limits (3.5-5.0 g/dl)
- Serum creatinine within normal limits (0.7-1.7 mg/ml)
- Absence of other known causes of liver disease (e.g. autoimmune hepatitis, hemochromatosis, Wilson's diseases, alpha-1 anti-trypsin deficiency, drug-induced liver injury, alcoholic liver disease)
- No other systemic antiviral or immunosuppressive therapy within the last 6 months
- Absence of concurrent medical and psychiatric illnesses (e.g. other viral co-infection such as HBV or HIV, renal failure, poorly controlled diabetes, cardiac-pulmonary diseases, CNS disease, active alcoholism, depression, psychosis)
- No history of Type 1 or Type 2 diabetes mellitis
- TSH within normal limits (0.49-4.7 micro IU/ml)
- ANA <1:160
- No history of hepatocellular carcinoma
- Alpha fetoprotein within normal limits (0-20 ng/ml) obtained within 6 months of enrollment.
- If participating in sexual activity that could lead to pregnancy, the study volunteer must agree that two reliable methods of contraception will be used with his partner simultaneously while receiving medication, and for 6 months after stopping the medications. The following are considered reliable and effective methods of birth control.
- 1) Condoms with or without a spermicidal agent 2) Diaphragm or cervical cap with spermicide 3) IUD 4) Hormonal-based contraception 16. Exceptions may include if study participant/partner is surgically sterile 17. Willingness to comply with procedures and treatment as outlined in the protocols and provide written informed consent
Who cannot join
- Interferon or ribavirin therapy at any previous time
- Any investigational drug <= 24 weeks prior to the first dose of study drug
- Any alternative or folk medicine within 24 weeks of screening
- Any systemic antiviral therapy <= 24 weeks prior to the first dose of study drug or expectation that such treatment will be needed at any time during the study. Exception: patients who have taken or are expected to require acyclovir for herpetic lesions
- Patient with a baseline increased risk for anemia (e.g. hemoglobinopathies such as thalassemia, spherocytosis, sickle cell anemia or a history of symptomatic recurring GI bleeding, etc.) or for whom anemia would be medically problematic
- Evidence of alcohol and/or drug abuse within 6 months
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- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, clinical evidence of rheumatoid arthritis)
- Evidence of an active or suspected cancer or a history of malignancy
- History of having received any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) <= 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
- History of major organ transplantation with an existing functional graft
- History of bone marrow transplantation
- Anything that in the opinion of the investigator puts the patient at increased risk, or increases the likelihood that the patient may not be able to complete the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas Medical Branch
Galveston, Texas, 77555
About this study
Official title: A Pilot Study to Characterize Interferon-Induced Gene Expression in Liver Cells and Peripheral Blood Lymphocytes Using High Density Oligonucleotide Microarray Expression Analysis in Caucasian and African American Patients With Chronic Hepatitis C
This proposal seeks to use DNA analyses to understand how racial and genetic factors influence interferon (treatment) response in HCV infection in African Americans. A better understanding should allow rational design of new therapies or better use of existing therapies. Patients will provide medical history and undergo a physical exam, blood draws, electrocardiogram, possible chest x-ray, and abdominal ultrasound. Patients will be admitted to the hospital for 5 days and undergo 2 liver biopsies, sedation, and multiple blood draws. Twenty adult male volunteers (10 Caucasians,10 African Americans) ages 18 - 65 years will participate.
Read the detailed description
This proposal uses sophisticated DNA microarray analyses of the transcriptional changes induced in hepatocytes (cellular locus of viral replication) and peripheral blood lymphocytes (one compartment of immune responder cells) in an effort to better understand how racial and host genetic factors influence interferon response in HCV infection. A better understanding of these underlying mechanisms should allow rational design of new therapies or better use of existing therapeutic modalities. The variables to be investigated are racial differences in interferon induced: 1) HCV viral kinetics and 2) intrahepatic and PBL transcriptional responses. Specific Aim 1: (a) To compare the phase 1 and early phase 2 decline of the viral titer in serum in African-Americans and Caucasians following a single dose of IFN-alpha (10 MU sc). (b) To determine the hepatic HCV RNA abundance in both a baseline liver biopsy and in a repeat liver biopsy taken 24 hrs after administration of interferon, and to determine how this correlates with the HCV RNA decline in serum over the 24 hr period. (c) To compare the rates of viral decline in the liver and serum in African-Americans and Caucasians 24 hours after interferon, and to relate this to the pharmacokinetics (PK) of the initial dose of interferon. A total of 10 Caucasian and 10 African American patients with chronic hepatitis C and HCV genotype 1 will be enrolled in this study. All study patients will undergo a baseline percutaneous liver biopsy on day 1 of the study. On day 3, a single dose of IFN-alpha 2a (10 MU sc) will be administered and a repeat liver biopsy will be done 24 hours after the injection. Specific Aim 2: (a) To utilize Affymetrix HG-U133A\&B Human GeneChips® to determine global mRNA profiles in liver tissue collected from patients before and 24 hrs after a single 10 MU dose of IFN-alpha and thereby assess the intrahepatic transcriptional response to IFN-alpha. (b) To characterize differences in the early intrahepatic transcriptional response to interferon in Caucasians and African Americans. Specific Aim 3: (a) To utilize Affymetrix HG-U133A\&B Human GeneChips® to determine global transcription profiles in peripheral blood lymphocytes pre-treatment, 24hrs, and 48hrs after the initial dose of interferon and to compare these results in Caucasians and African Americans at these time points. (b) To compare global gene profiles in lymphocytes and liver at baseline and 24hrs after interferon, and determine whether lymphocytic transcriptional profiling is a valid surrogate for intrahepatic gene profiling. Specific Aim 4: To use sophisticated bioinformatics approaches and HCV kinetic modeling to determine whether differences in early intrahepatic or lymphocytic transcriptional profiles correlate with early changes in the level of viremia (observed antiviral response) in the period immediately following administration of the 10 MU dose of IFN-alpha.
- Conditions
- Hepatitis C
- Being tested
- Interferon alpha
- Keywords
- Interferon, Gene Expression in Liver, Lymphocytes, High Density Oligonucleotide Microarray Expression Analysis, African American, Hepatitis C
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon alphaDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startMay 2006
- Study completionJun 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00324389
- Sponsor's protocol ID
- 04-014
- Status last verified
- Apr 2009
- First submitted
- 9 May 2006
- Last updated
- 27 Aug 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Characterize Interferon-Induced Gene Expression in Liver Cells and Peripheral Blood Lymphocytes Using High Density Oligonucleotide Microarray Expression Analysis in Caucasian and African American Patients With Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT00324389
- Acronym / sponsor ID
- 04-014
- Conditions
- Hepatitis C
- Keywords
- Interferon, Gene Expression in Liver, Lymphocytes, High Density Oligonucleotide Microarray Expression Analysis, African American, Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2006
- Study completion
- Jun 2006
- First posted
- 11 May 2006 (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 proposal seeks to use DNA analyses to understand how racial and genetic factors influence interferon (treatment) response in HCV infection in African Americans. A better understanding should allow rational design of new therapies or better use of existing therapies. Patients will provide medical history and undergo a physical exam, blood draws, electrocardiogram, possible chest x-ray, and abdominal ultrasound. Patients will be admitted to the hospital for 5 days and undergo 2 liver biopsies, sedation, and multiple blood draws. Twenty adult male volunteers (10 Caucasians,10 African Americans) ages 18 - 65 years will participate.
Detailed description
This proposal uses sophisticated DNA microarray analyses of the transcriptional changes induced in hepatocytes (cellular locus of viral replication) and peripheral blood lymphocytes (one compartment of immune responder cells) in an effort to better understand how racial and host genetic factors influence interferon response in HCV infection. A better understanding of these underlying mechanisms should allow rational design of new therapies or better use of existing therapeutic modalities. The variables to be investigated are racial differences in interferon induced: 1) HCV viral kinetics and 2) intrahepatic and PBL transcriptional responses. Specific Aim 1: (a) To compare the phase 1 and early phase 2 decline of the viral titer in serum in African-Americans and Caucasians following a single dose of IFN-alpha (10 MU sc). (b) To determine the hepatic HCV RNA abundance in both a baseline liver biopsy and in a repeat liver biopsy taken 24 hrs after administration of interferon, and to determine how this correlates with the HCV RNA decline in serum over the 24 hr period. (c) To compare the rates of viral decline in the liver and serum in African-Americans and Caucasians 24 hours after interferon, and to relate this to the pharmacokinetics (PK) of the initial dose of interferon. A total of 10 Caucasian and 10 African American patients with chronic hepatitis C and HCV genotype 1 will be enrolled in this study. All study patients will undergo a baseline percutaneous liver biopsy on day 1 of the study. On day 3, a single dose of IFN-alpha 2a (10 MU sc) will be administered and a repeat liver biopsy will be done 24 hours after the injection. Specific Aim 2: (a) To utilize Affymetrix HG-U133A\&B Human GeneChips® to determine global mRNA profiles in liver tissue collected from patients before and 24 hrs after a single 10 MU dose of IFN-alpha and thereby assess the intrahepatic transcriptional response to IFN-alpha. (b) To characterize differences in the early intrahepatic transcriptional response to interferon in Caucasians and African Americans. Specific Aim 3: (a) To utilize Affymetrix HG-U133A\&B Human GeneChips® to determine global transcription profiles in peripheral blood lymphocytes pre-treatment, 24hrs, and 48hrs after the initial dose of interferon and to compare these results in Caucasians and African Americans at these time points. (b) To compare global gene profiles in lymphocytes and liver at baseline and 24hrs after interferon, and determine whether lymphocytic transcriptional profiling is a valid surrogate for intrahepatic gene profiling. Specific Aim 4: To use sophisticated bioinformatics approaches and HCV kinetic modeling to determine whether differences in early intrahepatic or lymphocytic transcriptional profiles correlate with early changes in the level of viremia (observed antiviral response) in the period immediately following administration of the 10 MU dose of IFN-alpha.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Male non-Hispanic African-American or non-Hispanic Caucasian patients between 18 and 65 years of age
- Abstinence from any ingestion of alcohol and smoking for at least 7 days prior to study for those who drink or smoke socially
- HCV genotype 1 (1a, 1b or mixture of 1a and 1b). HCV genotyping will be performed at the Molecular Diagnostic Laboratory at UTMB using the LiPA assay (Innogenetics)
- Presence of HCV RNA in serum (>10 [to the fifth power] copies/ml)
- Not previously treated with any interferon and/ or ribavirin
Key exclusion criteria (12 listed)
- Interferon or ribavirin therapy at any previous time
- Any investigational drug <= 24 weeks prior to the first dose of study drug
- Any alternative or folk medicine within 24 weeks of screening
- Any systemic antiviral therapy <= 24 weeks prior to the first dose of study drug or expectation that such treatment will be needed at any time during the study. Exception: patients who have taken or are expected to require acyclovir for herpetic lesions
- Patient with a baseline increased risk for anemia (e.g. hemoglobinopathies such as thalassemia, spherocytosis, sickle cell anemia or a history of symptomatic recurring GI bleeding, etc.) or for whom anemia would be medically problematic
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 |
|---|---|---|
| Interferon alpha | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2010.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Interferon alpha in people with Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 23 inclusion and 12 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 27 Aug 2010. 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
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 27 Aug 2010.