Interferon-Induced Gene Expression in Liver Cells and Peripheral Blood Lymphocytes

• Status: Completed
• Trial end date: 2006-06-01
• Target enrollment: 0
• Participant gender: Male

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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Interferon-alpha; Interferons

Criteria

Inclusion Criteria:

1. Male non-Hispanic African-American or non-Hispanic Caucasian patients between 18 and 65 years of age

2. Abstinence from any ingestion of alcohol and smoking for at least 7 days prior to study for those who drink or smoke socially

3. 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)

4. Presence of HCV RNA in serum (>10 [to the fifth power] copies/ml)

5. Not previously treated with any interferon and/ or ribavirin

6. Compensated liver disease with the following laboratory criteria:

• 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)

7. 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)

8. No other systemic antiviral or immunosuppressive therapy within the last 6 months

9. 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)

10. No history of Type 1 or Type 2 diabetes mellitis

11. TSH within normal limits (0.49-4.7 micro IU/ml)

12. ANA <1:160

13. No history of hepatocellular carcinoma

14. Alpha fetoprotein within normal limits (0-20 ng/ml) obtained within 6 months of enrollment.

15. 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

Exclusion Criteria:

1. Interferon or ribavirin therapy at any previous time

2. Any investigational drug <= 24 weeks prior to the first dose of study drug

3. Any alternative or folk medicine within 24 weeks of screening

4. 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

5. 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

6. Evidence of alcohol and/or drug abuse within 6 months

7. 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)

8. Evidence of an active or suspected cancer or a history of malignancy

9. 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

10. History of major organ transplantation with an existing functional graft

11. History of bone marrow transplantation

12. 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