Vitamin D + Telaprevir + Peginterferon + Ribavirin for of Hepatitis C Genotype 1

Study Overview
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Brief Summary
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This study is for people who have been diagnosed with chronic hepatitis C, specifically those who have a certain type of the virus, genotype 1, and who have not yet received treatment for hepatitis C. This pilot study is designed to test whether the addition of vitamin D, to the three drugs (Incivek (telaprevir), Pegasys (peginterferon alfa-2a), and ribavirin) that are approved by the Food and Drug Administration (FDA) for the treatment of hepatitis C, can help eliminate the HCV from the body. Currently, doctors are unsure if the addition of vitamin D to prescribed hepatitis C therapy will have any effects on how the body clears the virus. Once enrolled, participants will be randomly assigned (like flipping a coin) to receive telaprevir + peginterferon alfa-2a + ribavirin + vitamin D3 (treatment group) or telaprevir + peginterferon alfa-2a + ribavirin (control group). A total of 80 participants, of all races/ethnicities, will be included in this study, at 5 to 10 VA hospital study sites (10 - 20 participants/site). Participants assigned to the treatment group will begin a lead-in phase where they will receive 5,000 IU of vitamin D3 per day. Every two weeks during the lead-in phase, participants will be tested to determine the Vitamin D level in their blood, as well as other tests, including HCV RNA (to determine the amount of virus present) and calcium levels. Once an adequate level of Vitamin D is detected in participants' blood, participants will begin treatment with telaprevir + peginterferon alfa-2a + ribavirin + vitamin D3 (15,000 IU/week) for 12 weeks. Participants randomized to the control group will immediately begin treatment with telaprevir + peginterferon alfa-2a + ribavirin for 12 weeks. At the end of Week 12 the participants' involvement in the study will be complete. Adverse events and effects of vitamin D3 will be obtained by assessing participants' medical history, physical examination, and blood tests at clinic visits. HCV RNA will be assessed at Screening, Day 1, Week 2, 4, 8 and 12.

Official Title
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A Pilot Trial of the Safety and Efficacy of Telaprevir +Peginterferon +Ribavirin +Vitamin D3 Among Treatment-naive Veterans Infected With Genotype 1 Hepatitis C Virus

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Telaprevir
* Drug: Peginterferon alfa-2a
* Drug: Ribavirin
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Hepatitis C genotype 1 infection Treatment naïve Age >18 years Agree to genetic testing Exclusion Criteria: Liver disease other than from hepatitis C HCV infection with mixed genotypes Decompensated liver disease AFP>100ng/ml. Known HIV infection Serum 25(OH)D less than 12ng/ml or greater than 30ng/ml Regular vitamin D supplement use Regular calcium supplement use Refusal to abstain from vitamin D supplementation Current or past history of kidney stones Current use of any of the prohibited medications listed in section 5.5 and the INCIVEK® package insert. Need for therapeutic vitamin D or calcium (e.g. treatment for osteoporosis, osteomalacia, hyperparathyroidism etc.), in the opinion of the investigator Significant substance abuse within the past 6 months, Suicidal attempt in the past 10 years or suicidal ideation in past 3 months, or any other psychiatric condition that the investigator deems would make a subject unsuited for treatment with peginterferon or ribavirin. Confirmed or suspected malignancy, or history of malignancy within the past 3 years (except treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix) Any autoimmune disease not easily controlled (in the opinion of the investigator) Any condition resulting in malabsorption ( Poorly controlled thyroid disorder, or diabetes mellitus (HbA1c > 9) Glomerular diseases (e.g., glomerulosclerosis or glomerulonephritis) associated with a serum creatinine >1.5 times the upper limit of normal Current or history of any clinically significant cardiac abnormalities/dysfunction (eg, angina, congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy, significant arrhythmia) including current uncontrolled hypertension or history of use of antianginal agents for cardiac conditions (Inclusion will be considered if clearance by a cardiologist is obtained.) Receipt of an investigational drug within the past 30 days Females who have a positive pregnancy test at the time of screening, are breastfeeding or who anticipate pregnancy within the next 18 months, or men with pregnant partners Lack of agreement from subject to use two forms of acceptable contraception History or other evidence of any significant illness which, in the opinion of the investigator, would make the patient, unsuitable for the study Laboratory Exclusions Hemoglobin: <12gm/dl male or female Neutrophil: <1,200/mm3 Platelets: <90,000/mm3 INR: >1.5 Albumin: <3.2gm/dl Total Bilirubin: >2.0mg/dl HbA1c: >9.5% Serum Creatinine: >1.5 times the upper limit of normal Serum Calcium Within local laboratory normal range Parathyroid hormone (PTH) <10 or >55 pg/mL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VitD+telaprevir+peginterferon+ribavirin<br>Participants randomized to the treatment group will receive 5,000IU/day of vitamin D3 during the lead-in phase. When the serum 25(OH)D level is ≥35ng/ml the participant will begin telaprevir + vitamin D3 (15,000IU/week) + peginterferon alfa-2a (180ug/week) + weight based ribavirin treatment. | Drug: Telaprevir<br> <br> * Other names: Incivek;Drug: Peginterferon alfa-2a<br> <br> * Other names: Pegasys;Drug: Ribavirin<br> <br> Dietary Supplement: Vitamin D<br> <br> |
| Active Comparator: Telaprevir + Peginterferon + Ribavirin<br>Participants randomized to the control group immediately begin treatment with telaprevir + 180ug of peginterferon alfa-2a (Pegasys) per week and either weight based ribavirin. | Drug: Telaprevir<br> <br> * Other names: Incivek;Drug: Peginterferon alfa-2a<br> <br> * Other names: Pegasys;Drug: Ribavirin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA | Hepatitis C virus Ribonucleic Acid identifies the presence of Hepatitis C in the blood | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event profile | Cumulative record of unanticipated or unintended medical occurrences, not necessarily related to the study treatment. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Genotype 1, Vitamin D, treatment-naive