Chronic Hepatitis B Clinical Trial
Official title:
Evaluation of 4-Methylumbelliferone for Treatment of Chronic Hepatitis B (HBV) and Chronic Hepatitis C (HCV)
Verified date | April 2006 |
Source | MTmedical Institute of Health |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
Open-label studies, anecdotal reports, and in vitro scientific research indicate that
4-methylumbelliferone (active ingredient of the dietary supplement Heparvit®) may prevent
and reverse the symptoms and complications of chronic infection with hepatitis B virus
(HBV)and hepatitis C virus (HCV). This effect has been observed among naïve patients as well
as those who are non-responders to interferon, commonly used as first-line therapy for HBV
and HCV. In order to scientifically address the efficacy of this 4-methylumbelliferone on
chronic viral hepatitis, a randomized, placebo-controlled, blinded study is needed.
It is hypothesized that 4-methylumbelliferone may reduce the impact and aggressiveness of
HBV and HCV upon the liver, thereby slowing the progression to potentially life threatening
liver diseases such as cancer and cirrhosis. This is a preliminary study designed to
determine any indications under controlled conditions that may warrant further detailed
clinical studies.
Status | Active, not recruiting |
Enrollment | 160 |
Est. completion date | August 2007 |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - Serum ALT at least 1.5x the upper limit of normal - For chronic HBV: Known positive serum HBeAg for at least 6 months; Presence of HBV DNA in serum - For chronic HCV: Presence of anti-HCV in serum within 6 months of enrollment; Positive serum HCV RNA (enrollment) - Written informed consent Exclusion Criteria: - Treatment (within past 3 months) with interferon, ribavirin, lamivudine, entecavir, or adefovir dipivoxil - Current treatment with any drug or dietary supplement that could affect serum transaminase values (e.g., milk thistle) - Pregnancy or inability to practice contraception in patients capable of bearing or fathering children - Decompensated liver disease (as indicated by total bilirubin >4 mg/dL; albumin <3 g/dL; prolonged (>2 sec over control) prothrombin time; or history of bleeding esophageal varices, ascites or hepatic encephalopathy) - Active alcohol use, drug abuse, and/or psychiatric problems that, in the investigator's opinion, could interfere with participation in the study - Hepatitis D infection (for HBV-infected patients) |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University Health Center Downtown "Brady/Green", 527 North Leona, | San Antonio | Texas |
Lead Sponsor | Collaborator |
---|---|
MTmedical Institute of Health | BioMonde Preparations Limited, The University of Texas Health Science Center at San Antonio |
United States,
1: Epidemiology and Prevention of Vaccine-Preventable Diseases, 7th ed, Eds W. Atkinson, C. Wolfe, 2003, Department of Health and Human Services, Centers for Disease Control and Prevention.
10: Penn State College of Medicine. Hershey, PA: 2004. Cited 2004 Dec 29. Faculty Research Expertise Database. Available from: http://fred.hmc.psu.edu/ds/retrieve/fred/meshdescriptor/D006923
12: O’Kennedy R, Thornes RD, editors. Coumarins: Biology, Applications and Mode of Action. West Sussex, England: John Wiley & Sons; 1997. ISBN: 0-471-96997-4
20: Sun S, Kong LY, Zhang HQ, He SA, Niwa M. The asymmetric synthesis of linear dihydropyrano-coumarins for Alzheimer’s disease. Heterocycles 2004;63:271-82.
9: Penn State College of Medicine. Hershey, PA: 2004. Cited 2004 Dec 29. Faculty Research Expertise Database. Available from: http://fred.hmc.psu.edu/ds/retrieve/fred/meshdescriptor/D014468
Abate A, Dimartino V, Spina P, Costa PL, Lombardo C, Santini A, Del Piano M, Alimonti P. Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study. Drugs Exp Clin Res. 2001;27(5-6):223-31. — View Citation
Asmuth DM, Nguyen HH, Melcher GP, Cohen SH, Pollard RB. Treatments for hepatitis B. Clin Infect Dis. 2004 Nov 1;39(9):1353-62. Epub 2004 Oct 12. Review. — View Citation
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. — View Citation
Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN. Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Curr Pharm Des. 2004;10(30):3813-33. Review. — View Citation
Kawase M, Tanaka T, Sohara Y, Tani S, Sakagami H, Hauer H, Chatterjee SS. Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter pylori activity. In Vivo. 2003 Sep-Oct;17(5):509-12. — View Citation
Kudo D, Kon A, Yoshihara S, Kakizaki I, Sasaki M, Endo M, Takagaki K. Effect of a hyaluronan synthase suppressor, 4-methylumbelliferone, on B16F-10 melanoma cell adhesion and locomotion. Biochem Biophys Res Commun. 2004 Sep 3;321(4):783-7. — View Citation
Lacy A, O'Kennedy R. Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer. Curr Pharm Des. 2004;10(30):3797-811. Review. — View Citation
Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. Review. — View Citation
Lopez-Gonzalez JS, Prado-Garcia H, Aguilar-Cazares D, Molina-Guarneros JA, Morales-Fuentes J, Mandoki JJ. Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer. 2004 Mar;43(3):275-83. — View Citation
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. — View Citation
Müller MJ, Fenk A, Lautz HU, Selberg O, Canzler H, Balks HJ, von zur Mühlen A, Schmidt E, Schmidt FW. Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis. Am J Physiol. 1991 Mar;260(3 Pt 1):E338-44. — View Citation
NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements. 2002 Jun 10-12;19(3):1-46. Review. — View Citation
Pearlman BL. Hepatitis C treatment update. Am J Med. 2004 Sep 1;117(5):344-52. Review. — View Citation
Rilla K, Pasonen-Seppänen S, Rieppo J, Tammi M, Tammi R. The hyaluronan synthesis inhibitor 4-methylumbelliferone prevents keratinocyte activation and epidermal hyperproliferation induced by epidermal growth factor. J Invest Dermatol. 2004 Oct;123(4):708-14. — View Citation
Shaw T, Bowden S, Locarnini S. Chemotherapy for hepatitis B: new treatment options necessitate reappraisal of traditional endpoints. Gastroenterology. 2002 Dec;123(6):2135-40. Review. — View Citation
* Note: There are 20 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Reduction of virus in blood to undetectable levels; | |||
Primary | Normalization of serum ALT and AST. | |||
Secondary | Reduced viral loads; Improvement of serum ALT and AST; | |||
Secondary | Improvement in general health status; | |||
Secondary | Improvement in serum marker of hepatic fibrosis; | |||
Secondary | Loss of HBeAg/seroconversion to HBeAb (for HBV patients). |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04496882 -
Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue
|
Phase 4 | |
Completed |
NCT04083716 -
A Study to Assess the Relative Bioavailability and Food Effect of ABI-H2158 in Healthy Adults
|
Phase 1 | |
Not yet recruiting |
NCT03038802 -
A Randomised Controlled Phase 1 Study of Vaccine Therapy for Control or Cure of Chronic Hepatitis B Virus Infection
|
Phase 1/Phase 2 | |
Completed |
NCT05310487 -
Phase 1 Study of 162, a Novel Neutralizing Antibody Targeting Hepatitis B Surface Antigen, in Healthy Adult Subjects
|
Phase 1 | |
Recruiting |
NCT06070051 -
Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy
|
Phase 1 | |
Terminated |
NCT05001022 -
A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects
|
Phase 1 | |
Recruiting |
NCT04139850 -
The Establishment of Korean Hepatitis B Patients Cohort
|
||
Recruiting |
NCT05343481 -
Efficacy of VTP-300 in Chronic Hepatitis B Infection
|
Phase 2 | |
Not yet recruiting |
NCT05490836 -
Functional Cure Rate of Peg-IFNα-2b Combined With TAF in HBeAg Negative CHB Patients
|
N/A | |
Recruiting |
NCT04543565 -
Pradefovir Treatment for the Patients With Chronic Hepatitis B Virus Infections: a Phase3 Study
|
Phase 3 | |
Active, not recruiting |
NCT02894918 -
A Study to Evaluate Addition of Peginterferon Alfa-2a to Chronic Hepatitis B (CHB) Patients Treated With NAs
|
Phase 4 | |
Not yet recruiting |
NCT02793791 -
Prophylactic Treatment of Hepatic Dysplastic Nodules in HBsAg Positive Patients
|
N/A | |
Recruiting |
NCT02287857 -
Efficacy and Safety of Domestic Tenofovir Tablets in Chinese Patients With Chronic Hepatitis B
|
N/A | |
Recruiting |
NCT01965418 -
A Clinical Evaluation on Traditional Chinese Medicine Diagnosis and Treatment Program Blocking and Reversing Hepatitis B-related Liver Fibrosis - a Randomized, Controlled, Double-blind, Multi-center Clinical Trial
|
Phase 4 | |
Recruiting |
NCT01491295 -
Switch to Tenofovir Versus Continue Lamivudine/Adefovir Treatment in Lamivudine-resistance Chronic Hepatitis B Patients
|
Phase 4 | |
Terminated |
NCT01872988 -
Tenofovir Antiviral Therapy Following Transarterial Chemoembolization for HBV Related Hepatocellular Carcinoma
|
Phase 3 | |
Recruiting |
NCT01487876 -
Efficacy and Safety of Dual-plasmid Hepatitis B Virus DNA Vaccine in Chronic Hepatitis B Patients
|
Phase 2 | |
Completed |
NCT01531166 -
A Cohort Study in Korean Patients With Chronic Hepatitis B (CHB) Receiving Pegylated Interferon
|
N/A | |
Not yet recruiting |
NCT01436539 -
Study of Effects and Safety Between Adefovir Dipivoxil Plus Polyene Phosphatidylcholine Versus Adefovir Dipivoxil Alone in Chronic Hepatitis B Patients
|
Phase 4 | |
Recruiting |
NCT01360892 -
Prediction of Incidence of Liver Cancer by Use of Real-time Tissue Elastography
|
N/A |