A Phase 1 Study of Quercetin in Patients With Hepatitis C
18 Years
65 Years
Both
Chronic Hepatitis C
Trial Information
A Phase 1 Study of Quercetin in Patients With Hepatitis C
Chronic hepatitis C (HCV) is a serious chronic condition in the United States affecting
millions of people and is the cause of rates of hepatocellular carcinoma recently doubling
in the US. Treatment of hepatitis C is proven to be an effective secondary prevention of
liver cancer. Current standard antiviral treatments exclude 70-80% of hepatitis C patients
from therapies due to intolerable side effects. Our laboratory efforts identified a
potential novel approach to hepatitis C treatment and hepatocellular carcinoma prevention
with Quercetin, a heat shock protein inhibitor.
This is a Phase I study evaluating the safety and tolerability of Quercetin in hepatitis C
patients who have contraindications to standard antiviral treatment (both treatment naïve
patients who decline standard therapy, patients who previously had standard treatments with
relapse, as well as those who had intolerable side effects previously). The investigators
recently demonstrated that the flavonoid Quercetin inhibits hepatitis C viral production in
tissue culture, at least partially through its inhibition of heat shock protein expression.
This represents a novel mechanism for treating hepatitis C infection. Quercetin also has
low toxicity. These promising characteristics motivate the proposed Phase I study.
Patients will be recruited through the UCLA Pfleger Liver Institute and treated on an
outpatient basis. Toxicity will be closely monitored and reported. Viral load response
will be evaluated as a secondary endpoint. The anticipated total number of patients
enrolled in the trial will be 20. All patients will be followed for 8 months after taking
this first dose of study medication. Patients exhibiting a viral load response will have
extended follow-up, ranging from a total follow-up of 12-24 months, to determine persistence
of this response.
Inclusion Criteria:
- All participants will have detectable HCV RNA in serum; stable viral load within the
previous year (no fluctuation > 2 log scale).
- All participants are either treatment-naïve and unwilling to be treated with standard
HCV therapies, or were not able to tolerate hepatitis C antiviral due to side effects
and completed treatment more than 6 months prior to enrollment into our trial.
- Age range will be from 18-65 years old
- ECOG performance status <2 (Karnofsky >60%)
- Life expectancy of greater than 12 months
- Participants must have:
- leukocytes >3,000/mcL
- absolute neutrophil count >1,500/mm(3)
- hemoglobin >13 or >12 g/dL for men/women
- platelets >125,000 K/mm(3)
- total bilirubin <1.5 g/dL
- AST(SGOT)/ALT(SGPT) <10 X institutional upper limit of normal
- Albumin >3.4g/dL
- INR <1.2
- Alpha Feto-protein <50 ng/mL
- creatinine within normal institutional limits OR
- creatinine clearance >60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.
- All participants must exhibit the ability to understand and the willingness to sign a
written informed consent document.
Exclusion Criteria:
- Participants who are currently on interferon +/- ribavirin or any other anti-viral
therapies are excluded from our study. Participants who have previously been treated
with hepatitis C antiviral therapy must have recovered from any adverse events due to
the agent(s) administered. In addition, their last antiviral therapy must be more
than six months prior to their enrollment in our study
- Participants may not be receiving any other investigational agents
- Participants with decompensated liver disease or cirrhosis will be excluded from this
trial
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Quercetin or any bioflavonoid agent
- According to a monogram published by the Natural Medicines Comprehensive Database,
drug interactions with Quercetin have been reported to occur with quinolone
antibiotics and inhibition of p-glycoprotein or various cytochrome P450 enzymes
including CYP3A4/ CYP2C8/ CYP2C9/ CYP2D6. Quercetin interactions with drugs can be
categorized into (1) moderate interaction to be avoided based on healthy volunteer
studies and (2) moderate interaction to be monitored closely based on in vitro
studies demonstrating potential theoretical reduced elimination and increased
effects. Screening will be performed prior to treatment.
- Participants with concurrent illness including but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris,
untreated/active cardiac arrhythmia, psychiatric illness, active moderate alcohol
use, or any social situation that would limit compliance with study protocol will be
excluded from our study.
- In addition, participants with any other known hepatitis etiologies (hepatitis B
co-infection, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson Disease,
autoimmune hepatitis, alcohol, drug, obesity induced liver disease); or those with
hepatocellular carcinoma will be excluded from this study.
- Pregnant women are excluded from this study.
- Human immunodeficiency virus (HIV)-positive subjects are excluded from our study.
- In addition to renal and hepatic laboratory requirements listed above, renal and
liver transplant recipients will be excluded from our study.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Outcome Measure:
Adverse Event Score Assessment of Quercetin Given over 28 days in hepatitis C patients who have contraindications to standard antiviral treatment
Outcome Description:
Primary outcome for the study will be safety. The investigators will track various laboratory parameters including viral loads and see patients every 2 weeks during our drug phase which is 28 days. After that follow patients every month to see how long antiviral activity will persist if we do see a positive outcome.
Outcome Time Frame:
up to 32 weeks
Safety Issue:
Yes
Principal Investigator
Samuel W French, MD/PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of California, Los Angeles
Authority:
United States: Institutional Review Board
Study ID:
IRB#10-04-063-01
NCT ID:
NCT01438320
Start Date:
July 2011
Completion Date:
June 2012
Related Keywords:
- Chronic Hepatitis C
- Treatment naive
- Contraindications to standard therapies
- Alternative hepatitis C therapy
- Hepatitis
- Hepatitis A
- Hepatitis, Chronic
- Hepatitis C
- Hepatitis C, Chronic
Name | Location |
|---|---|
| UCLA Jonsson Comprehensive Cancer Center. Factor Building | los Angeles, California 90095 |
