Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00225537
Status:
UNKNOWN
Last Update Posted:
2006-09-11
First Post:
2005-06-30
Brief Title:
4-Methylumbelliferone as a Treatment for Chronic HBVHCV
Sponsor:
MTmedical Institute of Health
Organization:
MTmedical Institute of Health
Study Overview
Official Title:
Evaluation of 4-Methylumbelliferone for Treatment of Chronic Hepatitis B HBV and Chronic Hepatitis C HCV
Status:
UNKNOWN
Status Verified Date:
2006-04
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 HBVand 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
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
Detailed Description:
i Chronic hepatitis B
Chronicity of HBV following acute infection is strongly age-related the majority 90 of infants acquiring HBV perinatally go on to develop chronic infection while most persons who acquire HBV later in life resolve their infection ref 1 Patients with chronic HBV have a 15-25 lifetime risk of liver cirrhosis and hepatic cancer An estimated 5000 people die each year from complications of chronic HBV infection cirrhosis and hepatocellular carcinoma
Three drugs have been approved by the Food and Drug Administration FDA for treatment of chronic HBV interferon-α IFN-α lamivudine and adefovir dipivoxil Only one-third of chronic HBV patients develop a sustained response to IFN-α treatment and adverse effects are common ref 2 Use of the newer orally-administered nucleoside analogues lamivudine or adefovir dipivoxil typically causes rapid initial clearance of virus and is associated with fewer adverse effects however seroconversion rates are low and long-term therapy with lamivudine required for sustained responses frequently results in resistance ref 2 Adefovir dipivoxil has so far not shown the high rate of resistance observed with lamivudine but it is expected that resistance will eventually develop ref 3 In summary major problems with currently approved therapy of HBV include expense toxicity and development of resistance
ii Chronic hepatitis C
Chronic viral hepatitis due to hepatitis C is an enormous medical problem affecting approximately 170 million people worldwide WHO ref 4 In the US an estimated 27 million people suffer from chronic HCV with 10000-12000 deaths per year attributable to the disease ref 5 Chronic HCV infections in the US are usually acquired through injectable drug use sexual contact or receipt of contaminated blood products before antibody screening was initiated in 1990 Most persons exposed to HCV 75 develop asymptomatic chronic infection Eventually 15-20 will die of cirrhosis and liver cancer without intervention ref 4
Only two drugs are licensed for treatment of chronic hepatitis C IFN-α standard or pegylated and ribavirin Sustained responses to IFN-α monotherapy have occurred in up to 35 of patients higher responses can be observed with combination treatment pegylated IFN-α and ribavirin ref 67 Responses to combination therapy is closely linked with HCV genotype types 2 and 3 most responsive A significant number of patients relapse or do not respond to standard treatment and retreatment is typically less effective than initial therapy ref 8
iii 4-methlyumbelliferone
Umbelliferones 7-hydroxycoumarins ref 9 are substances present in many species of plants especially umbelliferae fabaceae and oleaceae which include such common plants as manna ash sweet woodruff German chamomile celery parsley and others In nature umbelliferones help protect plants from cellular damage infestation trauma and infection Their 7-hydroxycoumarin derivatives 4-methylumbelliferones ref 10 are used in liver therapy as reagents plant growth factors sunscreens choleretics and spasmolytics They are also used as light-protective agents in the calibration of medical lasers and in analytical chemistry for the quantitation of nitric acid
Products containing 4-methylumbelliferone as their active substance have been available in the USA and Europe since 1990 as dietary supplements under trade names Heparvit Heparmed DetoxPro These products are promoted as supporting liver function and improving detoxification In many parts of Europe products containing 4-methylumbelliferone are also available as drugs and used as spasmolytics and choleretics ref 11 improving liver detoxification systems through increased bile production
7-hydroxycoumarins are also natural metabolites in the body that play important roles in the metabolism of ethanol chemotherapeutic drugs acetaminophen anabolic steroids and other hepatotoxic drugs ref 12 Indeed measurement of concentrations of 4-methylumbelliferyl glucuronide a metabolic product of 4-methylumbelliferone is a common assay for determining the level of toxicity of liver-toxic drugs ref 13
The broad potential medical benefits of 4-methylumbelliferone as a hepatoprotectant anti-inflammatory agent chemotherapeutic agent and antiviral substance have been described ref 1314 More recent studies indicate that 4-methylumbelliferone and other 7-hydroxycoumarin derivatives may be effective against Helicobacter pylori ref 15 several types of cancer ref 15-19 and Alzheimers disease ref 20
Chronicity of HBV following acute infection is strongly age-related the majority 90 of infants acquiring HBV perinatally go on to develop chronic infection while most persons who acquire HBV later in life resolve their infection ref 1 Patients with chronic HBV have a 15-25 lifetime risk of liver cirrhosis and hepatic cancer An estimated 5000 people die each year from complications of chronic HBV infection cirrhosis and hepatocellular carcinoma
Three drugs have been approved by the Food and Drug Administration FDA for treatment of chronic HBV interferon-α IFN-α lamivudine and adefovir dipivoxil Only one-third of chronic HBV patients develop a sustained response to IFN-α treatment and adverse effects are common ref 2 Use of the newer orally-administered nucleoside analogues lamivudine or adefovir dipivoxil typically causes rapid initial clearance of virus and is associated with fewer adverse effects however seroconversion rates are low and long-term therapy with lamivudine required for sustained responses frequently results in resistance ref 2 Adefovir dipivoxil has so far not shown the high rate of resistance observed with lamivudine but it is expected that resistance will eventually develop ref 3 In summary major problems with currently approved therapy of HBV include expense toxicity and development of resistance
ii Chronic hepatitis C
Chronic viral hepatitis due to hepatitis C is an enormous medical problem affecting approximately 170 million people worldwide WHO ref 4 In the US an estimated 27 million people suffer from chronic HCV with 10000-12000 deaths per year attributable to the disease ref 5 Chronic HCV infections in the US are usually acquired through injectable drug use sexual contact or receipt of contaminated blood products before antibody screening was initiated in 1990 Most persons exposed to HCV 75 develop asymptomatic chronic infection Eventually 15-20 will die of cirrhosis and liver cancer without intervention ref 4
Only two drugs are licensed for treatment of chronic hepatitis C IFN-α standard or pegylated and ribavirin Sustained responses to IFN-α monotherapy have occurred in up to 35 of patients higher responses can be observed with combination treatment pegylated IFN-α and ribavirin ref 67 Responses to combination therapy is closely linked with HCV genotype types 2 and 3 most responsive A significant number of patients relapse or do not respond to standard treatment and retreatment is typically less effective than initial therapy ref 8
iii 4-methlyumbelliferone
Umbelliferones 7-hydroxycoumarins ref 9 are substances present in many species of plants especially umbelliferae fabaceae and oleaceae which include such common plants as manna ash sweet woodruff German chamomile celery parsley and others In nature umbelliferones help protect plants from cellular damage infestation trauma and infection Their 7-hydroxycoumarin derivatives 4-methylumbelliferones ref 10 are used in liver therapy as reagents plant growth factors sunscreens choleretics and spasmolytics They are also used as light-protective agents in the calibration of medical lasers and in analytical chemistry for the quantitation of nitric acid
Products containing 4-methylumbelliferone as their active substance have been available in the USA and Europe since 1990 as dietary supplements under trade names Heparvit Heparmed DetoxPro These products are promoted as supporting liver function and improving detoxification In many parts of Europe products containing 4-methylumbelliferone are also available as drugs and used as spasmolytics and choleretics ref 11 improving liver detoxification systems through increased bile production
7-hydroxycoumarins are also natural metabolites in the body that play important roles in the metabolism of ethanol chemotherapeutic drugs acetaminophen anabolic steroids and other hepatotoxic drugs ref 12 Indeed measurement of concentrations of 4-methylumbelliferyl glucuronide a metabolic product of 4-methylumbelliferone is a common assay for determining the level of toxicity of liver-toxic drugs ref 13
The broad potential medical benefits of 4-methylumbelliferone as a hepatoprotectant anti-inflammatory agent chemotherapeutic agent and antiviral substance have been described ref 1314 More recent studies indicate that 4-methylumbelliferone and other 7-hydroxycoumarin derivatives may be effective against Helicobacter pylori ref 15 several types of cancer ref 15-19 and Alzheimers disease ref 20
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None