New website: NIH Clinical Research Trials and You

For Immediate Release
Monday, February 6, 2012

Contact:
NIH Office of Communications
301-496-5787

Agency-wide resource provides important information for the public and health care providers

The National Institutes of Health has created a new website, NIH Clinical Research Trials and You to help people learn more about clinical trials, why they matter, and how to participate. From the first cure of a solid tumor with chemotherapy to the use of nitroglycerin in response to heart attacks, clinical research trials — or research studies involving people — have played a vital role in improving health and quality of life for people around the globe.

Clinical trials are essential for identifying and understanding ways to prevent, diagnose, and treat disease. Research has shown that among the greatest challenges to recruitment of volunteers is the lack of general knowledge about what trials involve, where they are carried out, and who may participate.

"The ability to recruit the necessary number of volunteers is vital to carrying out clinical research that leads to health and medical advances," said NIH Director Francis S. Collins, M.D., Ph.D. "This new, centralized resource will make it much easier for the public and health professionals to learn about clinical trials and how people can participate in them."

Visitors to the website will find information about:

• The basics of clinical trial participation
• First hand experiences from actual clinical trial volunteers
• Explanations from researchers
• Links on how to search for a trial or enroll in a research matching program

In addition, health care professionals can read about evidence-based strategies for talking with patients about trials, print audience-tested posters to help promote trials in clinics and offices, and find other educational materials.

NIH supports clinical research trials across the country and throughout the world. NIH’s ongoing effort to raise awareness about clinical research and educate potential clinical trial participants about the option of a clinical trial is vital to developing public support and understanding for how clinical research drives medical discovery and improves health outcomes.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Low-protein diets for hepatic encephalopathy debunked: let them eat steak

Nutr Clin Pract. 2011 Apr;26(2):155-9.

Cabral CM, Burns DL.

Gastroenterology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805, USA. Chad.M.Cabral@Lahey.org

Abstract

Hepatic encephalopathy (HE) is an incompletely understood phenomenon and serves as a poor prognosis in patients with cirrhosis. Confusion from HE can affect the ability to eat adequately. Despite the prevalence of malnutrition in cirrhotic patients in the 1950s, it was reported that bouts of overt HE were controlled with low protein intake. This largely uncontrolled observation led to restriction of protein intake in cirrhotic patients with or without HE and was an accepted standard of care for many decades to follow. Published in 2004, the pivotal article "Normal Protein Diet for Episodic Hepatic Encephalopathy: Results of a Randomized Study" by Cordoba and colleagues was the first controlled study randomizing cirrhotic patients with HE to receive different amounts of dietary protein. At the completion of the study, the authors concluded that a normal-protein diet was safe and did not exacerbate HE. The Cordoba study suggests that low-protein diets should be abandoned. In light of this evidence, nutrition guidelines have proposed that protein restriction should be avoided in patients with HE as protein requirements are increased in cirrhosis. Despite the advice of experts in the field, it has been shown in recent years that some physicians still believe that protein restriction is needed in patients with HE. This belief has not been substantiated in controlled studies, and societal recommendations have changed. There is no real evidence documenting the advantages of protein restriction in HE. On the contrary, Cordoba and colleagues' article has shown that there are disadvantages to restricting protein in HE.

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Merck says hepatitis pill hampers HIV Drugs

By Ransdell Pierson

Thu Feb 9, 2012 2:37pm EST

(Reuters) - Merck & Co's recently approved Victrelis treatment for hepatitis C considerably lessens the effectiveness of some widely used medicines against the virus that causes AIDS, Merck and U.S. regulators said in separate reports.

"These drug interactions may be clinically significant for patients infected with both chronic hepatitis C virus and HIV by potentially reducing the effectiveness of these medicines when co-administered," Merck said in a February 6 letter to healthcare professionals.

Victrelis, approved last May, attacks the hepatitis C virus that over decades can lead to cirrhosis and liver failure. A significant percentage of hepatitis patients are also infected with the human immunodeficiency virus, or HIV, which weakens the immune system and is fatal without treatment.

The drug interactions were seen in a study among healthy volunteers who took Victrelis and the widely used HIV treatment Norvir in combination with one of three other anti-HIV pills: Reyataz (atazanavir), Prezista (darunavir) and Kaletra (lopinavir/ritonavir). All of the HIV drugs work by blocking protease, an enzyme the virus requires to replicate.

Victrelis reduced concentrations in the blood of Reyataz, Prezista and Kaletra by an average 49 percent, 59 percent and 43 percent, respectively.

Further, levels of Victrelis itself were reduced by 45 percent among volunteers who took it with Kaletra, and 32 percent among those who took it with a combination of Norvir and Prezista.

ISI Group analyst Mark Schoenebaum said 10 percent to 15 percent of patients with hepatitis C are co-infected with HIV, and the findings could crimp Victrelis sales by as much as 25 percent. But he said the setback would have little impact on Merck's earnings this year or in 2013.

The reduced prospects for Victrelis come even as its sales are being dwarfed by Vertex Pharmaceuticals Inc's Incivek, a rival protease inhibitor that was also approved last May.

The U.S. Food and Drug Administration, in an announcement of the findings that appeared on the agency's website on Wednesday, said patients should not stop taking any of their medicines without talking to healthcare professionals.

Drug interactions had previously been found between Victrelis and another HIV treatment called Sustiva (efavirenz). Sustiva belongs to a family of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Merck said it was conducting drug-interaction studies of Victrelis with other HIV drugs. They include Intelence (etravirine), which is also a NNRTI, and Isentress (raltegravir), which belongs to a class of drugs called HIV integrase inhibitors,

Merck shares slid 14 cents to $38.28 in afternoon trading on the New York Stock Exchange.

(Reporting By Ransdell Pierson; editing by John Wallace and Maureen Bavdek)

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Also See: Victrelis (boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV) Protease Inhibitor Drugs: Drug Safety Communication - Drug Interactions

When Will We Have Interferon-Free Treatment for Hepatitis C?

From Medscape Gastroenterology > Ask the Experts

William F. Balistreri, MD

Authors and Disclosures

Posted: 02/09/2012

Question:

Is it true that we are close to treatment of patients with chronic hepatitis C virus (HCV) infection with an interferon-free regimen?

Response from William F. Balistreri, MD
Professor of Medicine, University of Cincinnati College of Medicine; Staff Physician, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

A New Era of Therapy

Combination therapy with pegylated interferon (PEG-IFN) and ribavirin long stood as the standard of care for chronic hepatitis C virus (HCV) infection. Although effective in achieving high rates of sustained virologic response (SVR), this combination regimen was associated with troublesome side effects.^[1] Therefore, the development of 2 effective protease inhibitors -- telaprevir and boceprevir -- was hailed as a new era of therapy for patients with HCV genotype 1 infection.^[2] These direct-acting antiviral agents act at specific steps in the viral lifecycle and allow more effective treatment with a shorter duration.

Telaprevir and boceprevir, linear inhibitors of the HCV nonstructural protein 3/4A (NS3/4A) serine protease, were approved by the US Food and Drug Administration for HCV treatment in May 2011. However, the recent American Association for the Study of Liver Diseases (AASLD) recommendations indicate that these direct-acting antiviral agents must be used in combination with PEG-IFN and ribavirin.^[1] This is far from the ideal regimen; because of poor tolerability, many treatment candidates will decide not to pursue treatment or to defer treatment until an IFN-free regimen is available.

An Ideal Strategy for HCV

It is true that an IFN-free regimen is "no longer a dream."^[3] It is now viewed as part of a larger goal: the development and validation of an ideal strategy to treat HCV infection. The long sought-after therapeutic objective is to define a strategy that would be highly effective against allHCV genotypes, simple (oral drugs only, low pill burden, and short duration), and safe and tolerable, with low rates of resistance emergence. The recommended strategy would also assess each potential treatment candidate for interleukin 28B genotype, which is a robust pretreatment predictor of SVR to therapy in patients with genotype 1 chronic HCV infection.^[1]

How close are we? Various compounds, encompassing at least 5 distinct drug classes, are currently under development for the treatment of chronic HCV infection, and the results of trials of several investigational agents were recently published.^[3-5] Many other drug trials were presented at The Liver Meeting 2011: The AASLD 62nd Annual Meeting. These drugs bring us one step closer to the long sought-after ideal: the ability to delete noisome IFN injections from treatment strategies.

Promising Preliminary Results

Let me illustrate by focusing on phase 2 studies presented by 2 groups who reported exciting preliminary results of an investigational agent (PSI-7977) even in the absence of IFN coadministration.^[6,7] PSI-7977, a uridine nucleotide analog polymerase inhibitor, is administered orally once daily and has strong antiviral activity against HCV genotype 1 when used in combination with PEG-IFN and ribavirin. A double-blind placebo-controlled dose-ranging study of PSI-7977 in patients with HCV genotype 1 documented a rapid virologic response (RVR) in 98% of patients, with an end-of-treatment response at 24 weeks in 91%.^[6] The RVR in the placebo group was 19%, and the end-of-treatment response was 50%. Of specific note, all patients with the difficult-to-treat interleukin 28B single-nucleotide polymorphism T/T mutation had an RVR -- all became HCV-negative by week 3, and 100% went on to achieve an SVR.

In another phase 2 study, this investigational compound allowed all patients to achieve an RVR. More than 80% of the treatment group had nondetectable HCV RNA at 2 weeks, and all patients had undetectable levels at 3 weeks.^[7] All patients achieved normalization of serum alanine aminotransferase levels. No serious adverse events were attributable to PSI-7977, and as expected, safety and tolerability were greatest in the IFN-free treatment group.

Thus, PSI-7977 exhibits high-potency antiviral activity against a broad range of HCV genotypes, has a high barrier to resistance, and has a reassuring safety profile. This drug also allowed a shorter duration of therapy for viral clearance. These studies support the continued exploration of this drug and related compounds -- alone, with other direct-acting antiviral agents, or with shorter duration of IFN therapy in patients with all HCV genotypes. Further studies will hopefully confirm the initial excitement and optimism and, of note, will document the spectrum of potential adverse effects.

Getting to IFN-Free Regimens

Within the next 5 years, IFN-free regimens may be a reality and available in the clinic. As Sharma and Lok^[3] stated, "[I]t is possible that some of these regimens will also be ribavirin free. This will be good news for patients who wish to be treated but have to defer treatment because of contraindications to use of PEG-IFN or ribavirin, or out of concerns about their ability to tolerate these medications." The ideal strategy is on the horizon.

References

1. Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433-1444. Abstract
2. Jensen DM. A new era of hepatitis C therapy begins. N Engl J Med. 2011;364:1272-1274. Abstract
3. Sharma P, Lok AS. Interferon-free treatment regimens for hepatitis C: are we there yet? Gastroenterology. 2011;141:1963-1967.
4. Gane EJ, Roberts SK, Stedman CA, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010;376:1467-1475. Abstract
5. Zuezem S, Asselah T, Angus P, et al. Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology. 2011;141:2047-2055. Abstract
6. Lawitz E, Lalezar JP, Hassanein T, et al. Once-daily PSI-7977 plus PEG/RBV in treatment-naive patients with HCV GT1: robust end of treatment response rates are sustained post-treatment. Program and abstracts of The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting; November 9-13, 2011; Boston, Massachusetts. Abstract 225.
7. Gane EJ, Stedman CA, Hyland RH, et al. Once daily PSI-7977 plus RBV: pegylated interferon-alfa not required for complete rapid viral response in treatment-naive patients with HCV GT2 or GT3. Program and abstracts of The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting; November 9-13, 2011; Boston, Massachusetts. Abstract 34.

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Tocotrienols Reach Organs, Impart Clinical Benefits

EDISON, NJ— A recently published human study reported orally supplemented tocotrienols (as Tocomin SupraBio®, from Carotech) are distributed to various tissues and vital organs and produce significant clinical benefits. Half of end-stage liver disease patients given the supplement for 12 weeks had a reduced Model for End Stage Liver Disease (MELD) score, while only 20 percent of patients taking tocopherols (the regular vitamin E) had similar score reductions.

The trial was conducted by Chandan K. Sen, Ph.D., and his team from the Ohio State University Medical Center and registered at NIH's ClinicalTirals.gov website. The study was designed to determine the levels of vitamin E isomers in human tissues and vital organs following oral supplementation with Tocomin SupraBio, a patented and bioenhanced natural full spectrum palm tocotrienol softgel.

Among the 80 total study subjects, one group of healthy participants had blood and skin tests and were then given 400 mg/d Tocomin for 12 weeks, while another group of surgical patients provided tissue samples of cardiac muscle, liver, abdominal adipose tissues, and brain tissues, and were randomized to either 400 mg/d tocotrienols (Tocomin) or tocopherols for a mean supplement duration of 20 weeks (range: one to 96 weeks).

The researchers found the healthy subjects had negligible levels of tocotrienols in both blood and skin prior to tocotrienols supplementation; after 12 weeks of supplementation, blood and skin levels of tocotrienols increased. In addition, the observed alpha-tocotrienol concentration in blood was 20-fold higher than the amount required to provide neuroprotection. Further, the adipose tissue in tocotrienol supplemented patients contained approximately 10-times the tocotrienol levels, compared to controls. Tocotrienol supplementation also significantly increased alpha, gamma, and delta-tocotrienol levels in the human brain. According to the researchers, alpha-tocotrienol was transported to human brain at a concentration reported to be neuroprotective in earlier studies. In both heart muscle and liver, alpha, gamma, and delta-tocotrienol levels were significantly higher in tocotrienol supplemented patients as compared to subjects receiving tocopherol alone.

As far as health benefits, the researchers utilized the MELD scoring system, which is clinically used to assess the severity of chronic liver disease—the higher the MELD score, the more severe the condition and increased urgency for liver transplantation. They noted MELD score is a reliable marker for mortality in end-stage liver disease. Over the period of the study the researchers noticed that tocotrienols supplemented end stage liver disease patients experienced a reduction in their MELD scores. Among subjects supplemented with tocopherol alone, only 20 percent (one out of five) experienced reduced MELD score, while 50 percent (seven out of 14) of the tocotrienol supplemented subjects showed MELD score improvement.

In fact, MELD score reduction associated with tocotrienol supplementation was most evident in patients with viral hepatic cirrhosis: four out of six patients (67 percent) with hepatitis C and one single hepatitis B patient had reduced MELD score. Researchers noted standard of care therapy is available for viral hepatitis, but it is poorly tolerated due to its toxicity and side effects.

“It is very exciting to learn from this human study that oral supplementation of bioenhanced palm tocotrienol complex that Tocomin SupraBio, improves accumulation of tocotrienols in the blood, skin, adipose, brain, heart and liver," said WH Leong, VP of Carotech. "The study also shows that Tocomin SupraBio® significantly lowered the MELD score in end stage liver disease patients. and may therefore be an exciting oral supplement with potential to benefit these patients. Tocopherol again did not show the same level of efficacy." He further stated this human study also proved tocotrienols are absorbed and accumulated in vital human organs even in the presence of tocopherol, thereby unequivocally dispelling claims that tocopherol prevents the absorption of tocotrienols.

Editor's Note: For more information on tocotrienols, check out INSIDER's On-Demand webinar entitled, "Partner Series—Natural Vitamin E Tocotrienol in Neuroprotection and Stroke Prevention," as well as the INSIDER Tocotrienols Solution Center , which includes slideshows and video from the recent SupplySide workshop on tocotrienols.

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Victrelis (boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV) Protease Inhibitor Drugs: Drug Safety Communication - Drug Interactions

[Posted 02/09/2012]

AUDIENCE: Infectious Disease, Pharmacy

ISSUE: FDA notified healthcare professionals and patients that drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together.

A drug interaction study showed that taking boceprevir (Victrelis) with ritonavir (Norvir) in combination with atazanavir (Reyataz) or darunavir (Prezista), or with Kaletra (lopinavir/ritonavir) reduced the blood levels of the HIV medicines and boceprevir in the body (see Data Summary below). FDA will be updating the Victrelis drug label to include information about these drug interactions.

BACKGROUND: Victrelis is a hepatitis C virus (HCV) protease inhibitor used with the medicines peginterferon alfa and ribavirin to treat chronic (long-lasting) hepatitis C infection in adults. HIV protease inhibitors are a class of anti-viral drugs used to treat HIV infection. Ritonavir is an HIV protease inhibitor used to “boost” other HIV protease inhibitors, increasing their levels in the blood and making them more effective.

RECOMMENDATION: Patients should not stop taking any of their medicines without talking to their healthcare professional. Patients should contact their healthcare professional if they have any questions or concerns.

Healthcare professionals who have started patients infected with both chronic HCV and HIV on Victrelis and antiretroviral therapy containing a ritonavir-boosted protease inhibitor should closely monitor patients for HCV treatment response and for potential HCV and HIV virologic rebound.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[02/09/2012 - Drug Safety Communication - FDA]

[02/06/2012 - Dear Healthcare Professional Letter - Merck]

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Chronic Liver Disease Foundation Issues Statement in Support of Birth-Cohort Screening for Hepatitis C

PRESS RELEASE

Feb. 9, 2012, 12:00 p.m. EST

Recommendations Include Expanded Testing with Rapid Point-of-Care HCV Test

CLARK, N.J., Feb 9, 2012 (GlobeNewswire via COMTEX) -- The Chronic Liver Disease Foundation (CLDF), a leading educational organization dedicated to increasing awareness of the effect of chronic liver disease (CLD) in the United States, issued today a position paper in support of expanding screening for hepatitis C (HCV) in the United States.

The position paper, "Endorsement of Birth-Cohort Approach to Expand Screening for Hepatitis C," outlines the CLDF's recommendations for a more effective strategy to identify patients with HCV infection and link such patients to expert care and treatment.

HCV is the most common blood-borne chronic viral infection in the U.S., with more than four million Americans currently infected with the HCV virus. Of these, up to 75 percent are unaware of their infection. Individuals born between the years of 1945 and 1965 have an HCV prevalence level four times higher than those born outside the birth cohort.

While the CDC currently recommends HCV screening only for individuals found to be at risk for the HCV infection, it is currently evaluating the potential benefits of using a birth-cohort based approach to HCV screening to help increase identification of HCV-positive patients.

The CLDF issued the following recommendations in support of the expansion of HCV screening efforts:

• Routine screening for HCV among persons born between 1945 and 1965
• Use of the OraQuick HCV rapid point-of-care test to expand testing opportunities and facilitate immediate care
• Educational programs aimed at primary care providers to increase awareness of HCV risk factors
• Testing for HCV in primary care setting with established linkages to HCV
• Creative ways to increase access to HCV testing and care for injection-drug users and other underserved populations.

"Today, more than 4 million Americans are infected with hepatitis C and the vast majority does not know it," said Dr. Willis C. Maddrey, President of the Chronic Liver Disease Foundation. "Hepatitis C is a leading cause of chronic liver disease, cirrhosis and liver cancer. However, new therapies are now available that can effectively treat a high percentage of people with HCV infection, making expanded and accessible testing for HCV -- particularly among those born between 1945 and 1965 -- a critical step in fighting this epidemic." 

About the Chronic Liver Disease Foundation

Established in 2001, the Chronic Liver Disease Foundation is a nonprofit 501(c)(3) educational organization dedicated to providing hepatology related continuing medical education, news and information to healthcare professionals across the US. The CLDF is led by a Board of Trustees comprised of nationally renowned liver disease specialists. Furthermore, the CLDF believes that educational programs should be developed by the specialists who are actively involved in the research, treatment and management of a disease. As such, the CLDF has developed a network of 75 Centers of Educational Expertise and multiple Advisory Boards who are actively involved in program creation related to specific disease topics which include: hemochromatosis, hepatic encephalopathy, hepatitis B, hepatitis C, hepatocellular carcinoma, HIV co-infection, liver transplantation and NASH/NAFLD. The CLDF's educational opportunities are offered in a variety of formats including an interactive web site, live meetings, teleconferences, print pieces, webcasts and other electronic mediums. For more information, please visit www.chronicliverdisease.org .

This news release was distributed by GlobeNewswire, www.globenewswire.com 

SOURCE: Chronic Liver Disease Foundation

        CONTACT: CLDF Media Contact:
        mediarelations@chronicliverdisease.org 
        888-565-5321
        
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