Clinical trial NCT01250743: A Pilot Study of High-Dose, Intravenous Ascorbic Acid (Vitamin C) to Treat Hepatitis C
Official title: An Open-Label Pilot Study of the Safety, Tolerability and Anti-Viral Activity of High Dose Intravenous Ascorbic Acid in Patients Chronically Infected With Hepatitis C Virus Genotype 1, Who Have Failed Prior Therapy With Interferon-alpha and Ribavirin
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatitis C
Keywords: genotype 1
Lead sponsor: Health Innovations, Frontier Research Institute
Sponsor class: OTHER
First posted: 2010-12-01
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this pilot study is to learn whether high doses of ascorbic acid (vitamin c), given intravenously to patients with chronic hepatitis due to infection with the genotype 1 version of the hepatitis C virus, are safe, well-tolerated and able to reduce the amount of virus circulating in the patients' blood.

Detailed description: Hepatitis C virus (HCV) chronically infects 1% to 3% of the world's population, including about 3.9 million infected patients in the United States, with an estimated 36,000 new cases in the US each year. 70-85% of infected individuals develop a chronic infection complicated by chronic liver disease during the next 20 to 30 years, which is the tenth leading cause of death in the US. HCV is implicated in the development of hepato-cellular carcinoma. Chronic HCV hepatitis is the most frequent reason for liver transplantation. HCV genotype 1 is the most common genetic variant of HCV causing HCV hepatitis in the US. It responds less well to conventional anti-HCV treatment than the other HCV genotypes, so that 60% of genotype 1 patients fail conventional therapy due to the virus's resistance to treatment and/or due to toxic side effects of the therapy.

Extracellular levels of ascorbic acid (vitamin c) attainable only by high-dose, intravenous administration, are reported to have in vitro and in vivo anti-cancer and anti-viral effects in humans and animals. Ascorbic acid briefly generates extracellular hydrogen peroxide, an oxidative stress specifically toxic to cancer cells and cells infected with viruses, including HCV, but not to normal cells. High-dose, intravenous ascorbic acid has been given to large numbers of patients, particularly cancer patients, with anecdotal reports of good safety and occasional benefit. Given the foregoing, the investigators propose that there is sufficient rationale for a careful pilot study of the safety and anti-viral efficacy of infused ascorbic acid in HCV genotype 1 hepatitis.

Eligibility criteria: Inclusion Criteria:

* hepatitis C, genotype 1
* failed treatment with interferon-alpha and ribavirin
* abstain from alcohol consumption for the duration of the study

Exclusion Criteria:

* cirrhosis
* decompensated liver disease
* glucose6phosphate dehydrogenase deficiency
* AST or ALT more than 5 times upper limit of normal
* platelets less than 125,000
* diabetes mellitus
* alcohol and/or drug abuse within 1 year of screening

Primary outcomes:
measure: number of participants with adverse events as a measure of safety and tolerability
timeFrame: 6 months
Secondary outcomes:
measure: anti-viral efficacy
timeFrame: 6 months
measure: aspartate aminotransferase (AST or SGOT)
timeFrame: 6 months
measure: alanine aminotransferase (ALT or SGPT)
timeFrame: 6 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center, Department of Integrative Medicine
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Jeanne A Drisko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Frontier Research Institute/Health Innovations
name: Michael A Catalano, MD
role: STUDY_DIRECTOR
affiliation: Frontier Research Institute/Health Innovations
name: Terry A Grossman, MD
role: STUDY_CHAIR
References:
citation: Choi J, Lee KJ, Zheng Y, Yamaga AK, Lai MM, Ou JH. Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells. Hepatology. 2004 Jan;39(1):81-9. doi: 10.1002/hep.20001.
citation: Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. doi: 10.1073/pnas.0506390102. Epub 2005 Sep 12.