Clinical Trial: Vit D Supplement + Peg Interferon

StephenW

    The Beneficial Effect of Vitamin D Supplement to Peg Interferon Alpha 2a or to Telbivudine Monotherapy in Patients With Chronic Hepatitis B Virus (HBV) Infection
                         This study is currently recruiting participants.   
                              Verified on March 2010 by Ziv Hospital   
            
      First Received on March 3, 2010.            Last Updated on January 17, 2011        History of Changes      
  

Sponsor:	Ziv Hospital
Information provided by:	Ziv Hospital
ClinicalTrials.gov Identifier:	NCT01083251

    Purpose  

Abstract

Telbivudine is a potent inhibitor of HBV but, due to a low genetic barrier to resistance, a high incidence of resistance has been observed in patients with high baseline levels of replication and in those with detectable HBV DNA after 24 weeks of therapy (A1). Telbivudine might be used in patients with good predictors of response (HBV DNA <2 X 106 IU/ ml, i.e. approximately 107 copies/ ml, or 6.3 log 10 IU/ ml at baseline) with verification of HBV DNA suppression below detection in real time PCR assay at 24 weeks.(EASL Guidelines for HBV 2009) The therapy of Pegylated-interferon-alpha-2a is considered as the standard of care for patients with chronic hepatitis b viral infection. However, recent study by Buster et al showed that a sustained viral response (SVR less than 2000 iu.ml at 6 months after treatment)) is obtained in 8 % of patients with genotype D, 30% genotype A, and 20-25% genotypes B or C (47). Vitamin D is a potent immune-modulator; and has been shown to improve SVR in combination with peg interferone in patients with chronic HCV viral infection (48). The impact of vitamin D on virologic response rates of interferon-based treatment of CHB is unknown. The aim of this study therefore was to assess whether Vitamin D, added to the conventional peg therapy in CHB, or to nucleotide analogues could improve the treatment efficacy

      

Condition	Intervention
Hepatitis B Virus	Drug: Peginterferon + Vitamin D                 Drug: Peginterferon                 Drug: Sebivo                 Drug: entecavir+ vitamin d

  
  
      

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Beneficial Effect of Vitamin D Supplement to Peg Interferon Alpha 2a or to Telbivudine Monotherapy in Patients With Chronic HBV Viral Infection

      
  Resource links provided by NLM:
  
MedlinePlus related topics:  Dietary Supplements   Hepatitis  Hepatitis A  Hepatitis B  Vitamin D         
Drug Information available for: Interferon alfa-2a Entecavir  Peginterferon Alfa-2a  Interferon alfa-n1              Vitamin D Telbivudine Interferons
U.S. FDA Resources   
   
        
  Further study details as provided by Ziv Hospital:
  
              Primary Outcome Measures:      

• treatment efficacy [ Time Frame: 120 weeks ] [ Designated as safety issue: No ]The primary end point will be sustained viral response which was defined as clearance of HBeAg from serum and HBV DNA less than 10,000 copies/mL (2000 IU/mL) at 6 months after treatment.  HBsAg titre during treatment and at 6 months follow up will be measured also (ROCH or Abott Kit).
  
  
• histologic response [ Time Frame: 120 WEEKS ] [ Designated as safety issue: No ]Another primary endpoint will be histologic response (reduction of at least two points without fibrosis worsening in the total score on the Histological Activity Index).
  
  
  

   
   
               

Estimated  Enrollment:	120
Study Start Date:	March 2010
Estimated  Study Completion Date:	December 2012
Estimated  Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

            

Arms	Assigned Interventions
Peg + Vitamin D: ExperimentalTreatment arm with vitamin D will be treated first with vitamin D supplement for 3 months before the initiation of antiviral therapy. Vitamin D levels will be measures at baseline and three months after. The serum vitamin D-25-OH levels should be > 32 ng/ml before the initiation of antiviral treatment). HBV DNA levels will be also measure at baseline and after 3 months of mono therapy with vitamin D Intervention: Drug: Peginterferon + Vitamin D	Drug: Peginterferon + Vitamin D180 mcg/week + 400 IUX2/day
Peginterferon: Active ComparatorIntervention: Drug: Peginterferon	Drug: Peginterferon180 mcg/week
Sebivo: Active ComparatorNucleotide Analog Telbivudine 600 mg daily Intervention: Drug: Sebivo	Drug: SebivoTelbivudine 600 mg daily
entecavir + vitamin d: Active Comparatorbaraclude 1 mg x1/ day + vitamin d Intervention: Drug: entecavir+ vitamin d	Drug: entecavir+ vitamin dentecavir 1 mg daily+ vitamin d

   
   
                              
  

      Eligibility

        

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

            Criteria
   

Inclusion Criteria:

• patients were eligible if they had been HBsAg positive for at least 6 months,
• patients were HBeAg positive or negative,
• patients had increased serum ALT levels between 1 and 10 times the upper limit of normal (ULN),
• patients had serum HBV-DNA levels greater than 1.0 x 10E5 copies/mL (2.0 X 10E4 IUmL), and
• patients had findings on a liver biopsy within the preceding 12 months that were consistent with the presence of chronic hepatitis B.
  

Exclusion Criteria:

• decompensated liver disease,
• antiviral therapy within 6 months before randomization,
• viral co-infections (hepatitis C virus, hepatitis delta virus, or human immunodeficiency virus), or
• pre-existent neutropenia or thrombocytopenia.
  

      

    Contacts and Locations
    Please refer to this study by its ClinicalTrials.gov identifier: NCT01083251

StephenW

谷歌翻译不是100％准确，仅供参考使用。

目的
摘要

替比夫定的HBV的强效抑制剂，但由于低耐药性的基因屏障，高的发病率一直在复制的高基线水平的患者，并在检测到HBV - DNA的观察治疗后24周（A1）的阻力。替比夫定可能被用来在与患者反应良好的预测（HBV DNA<2× 106 IU /毫升，即约107拷贝/毫升，或6.3日志基线10 IU/毫升）低于检测乙肝病毒DNA抑制核查实时PCR检测，在24周（2009年的HBV EASL指南）被认为是聚乙二醇干扰素α- 2a的治疗慢性乙型肝炎病毒感染患者的护理标准。然而，巴斯特等最近的研究表明，获得持续病毒反应（SVR低于2000 iu.ml治疗后6个月））基因型D患者的8％，30％的A基因型和20-25％基因型B或C（47）。维生素D是一种有效的的免疫调制器，并已被证明，以改善患者的慢性丙型肝炎病毒感染（48）与PEG interferone相结合的SVR。维生素D对干扰素治疗慢性乙型肝炎的病毒学应答率的影响是未知的。因此，本研究的目的是评估是否维生素D，添加到传统PEG在CHB治疗，或核苷酸类似物，可以提高治疗效果

StephenW

我想分享我们很好的朋友,Maureen, 以下两个在B型肝炎基金会(HBF)的博客。关于维生素D，请咨询自己的医生.
http://wp.hepb.org/

StephenW

Got HBV?  Adding Vitamin D to Your Diet                                                                                        Posted on August 25, 2011 by hepbtalk| Leave a comment                                                                                       
                                                                                       

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Do you have hepatitis B, and are you considering adding vitamin D to your diet?  Adding vitamin D seems to be a win-win for those with liver disease since it is a potent immune modulator, appears to aid in the prevention of cancer, and other potentially related disorders such as NAFLD, along with Type I and II Diabetes, glucose intolerance and metabolic syndrome.  Before you make any big additions, be sure to talk to your doctor or liver specialist to ensure it’s safe for you with your current health status.
Vitamin D is a fat soluble vitamin (needs a little fat to digest), versus a water soluble vitamin, that is ultimately stored in the liver.  There are pros and cons to this.  Fat soluble vitamins are not necessarily needed on a daily basis as they are stored in fatty tissues and in the liver making it available for longer periods of time.  Vitamin D is specifically stored in the liver. Unlike water soluble vitamins, excesses are not excreted through urine on a daily basis. That makes the balance a little trickier because you don’t want vitamin D accumulating in the liver and causing toxicity. Symptoms of vitamin D deficiency include osteomalacia, or softening of the bones, or perhaps less obvious bone pain and muscle weakness. Symptoms of vitamin D toxicity may include decreased appetite, nausea,vomiting, excess calcium blood levels or an accumulation of calcium in soft tissues. Too much of a good thing is NOT good for you!
Current guidelines for vitamin D intakeare 600 IU or 15 mcg per day. (See tablefor age specific info). Natural sources of vitamin D in foods (vitamin D2, or ergocalciferol) are hard to come by, but they are out there.  Mega sources include fatty fish like salmon, mackerel, and tuna.  Cod liver oil is an excellent source, which is probably why we see old movies with mom spooning cod liver oil into the mouths of young children! In the U.S. many dairy products, and others such as cereals, or orange juice are fortified with vitamin D and other vitamins. (There’s a great reason for the fortification of dairy with vitamin D – absorption is enhanced in the presence of calcium.) It is also found in smaller amounts in egg yolks. Naturally all of this needs to be balanced with the concerns of farm raised fish and possible exposure to PCBs, or mercury levels found in tuna, pollution of our oceans, raising your cholesterol levels due to focusing on the yolks, possible toxic levels of vitamin A with cod liver oil  (in Western countries where foods are fortified with vitamin A), or simply the bad, fishy taste associated with cod-liver oil. It’s a tough balance, but it’s important to work through some of the risks versus benefits in your own mind.
Sunshine is another readily available source of vitamin D (vitamin D3, cholecalciferol), but you need to be sure to balance it with the risk of over-exposure to the sun’s rays. And of course in the north, during the winter months, it may be difficult to get adequate sunshine to boost your vitamin D levels. You can get adequate sun exposure with 10-15 minutes in the sun, 3-5 times per week, with the exposure of face and arms. Naturally this will vary based on the sun’s intensity, how much skin is exposed and each individual’s skin tone, since the amount of necessary sun increases with the amount of melanin (pigment) in the skin.  Just to confuse matters, a recent study shows a possible link of higher levels of vitamin D to non-melanoma skin cancer, even though higher levels are thought to reduce the risk of basal cell cancer. Clearly more studies need to be done, but until that time, just keep reminding yourself that balance is important.
Sometimes it’s tough to get adequate vitamin D levels from natural sources such as food and sunshine, so there is the option for vitamin D supplements. This is where my anxiety levels intensify. Bad enough I have to worry about my food sources – PCBs from farm raised fish and such things, but now I have to choose a supplement – perhaps cod liver oil in a liquid or capsule that I can take daily.  Will it be in a form that is able to be absorbed?  (There’s a debate on the true benefit of cod liver oil once it is processed.  The same argument might apply to many available supplements.) How will I know this?  Will I break the bank trying to purchase these supplements?  I started to do the research on vitamin D supplementation, but like so many supplements, it’s very complex.  I always feel like I’m being sold. Using supplements is a personal thing. My personal preference would be to get my vitamin D through the foods I eat, and a short duration of sunshine.  However, I currently have adequate levels of vitamin D, so whatever I’m doing seems to be adequate.  That’s the key: tailoring your decisions based on you, your family history, or ethnicity and things you might be prone to such as a vitamin D deficiency, or other issues.
Please don’t forget to talk to your PCP and your liver specialist before drastically changing your vitamin D intake.  This is especially important if you are currently undergoing treatment for HBV.  Your doctor may wish to get a general baseline of your vitamin D levels, and continue to monitor them if there are problems.  Your doctor may be uncomfortable recommending a specific supplement since there is little or no regulation. Heed her advice before moving forward, and if you choose the supplementation route, be sure to do your homework to get the best quality product that is readily absorbable, without causing toxicity.
                                                                                       
                                                                                        This entry was posted in Adults, General Hep B info, Liver Health, Living with Hep B, Pediatrics and tagged HBV, Hepatitis B, liver, NAFLD, vitamin D. Bookmark the permalink.                                                                                       

StephenW

                                                                                                Hepatitis B and Vitamin D                                                                                        Posted on August 23, 2011 by hepbtalk| 1 Comment                                                                                       
                                                                                       

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Vitamin D is essential for everyone, but how might vitamin D help those living with HBV? Vitamin D is especially important for children and older adults, as it aids in the body’s absorption and regulation of calcium and phosphorus, which helps form and maintain healthy bones and teeth.  Vitamin D is also a potent immune modulator, and aids in the prevention of hypertension, and cancer. Vitamin D levels appear to play a critical role in type I and type II diabetes, glucose intolerance, and metabolic disorders.  Studies have also shown a link between low vitamin D levels and NAFLD (Non-alcoholic fatty liver disease), independent of metabolic syndrome, diabetes, or insulin-resistance profile (for those without HBV). The lower the vitamin D level, the higher the risk for NAFLD, or fatty liver disease.  The liver plays such an integral part in digestion, regulation, storage, and removal of toxins – the list goes on.  You can’t live without it!  As a result, it seems logical that healthy levels of vitamin D would benefit those living with HBV, if adequate vitamin D levels help reduce the risk of NAFLD, metabolic syndrome, etc.
Vitamin D is a potent immune modulator.  It has been on the radar for the prevention and treatment of infectious diseases for years. If you are being treated for HBV, you may want to discuss the potential benefits of adding vitamin D to your current therapy.  It has been shown to benefit hepatitis C patients undergoing treatment.  There is currently a clinical trial in Israel looking into the possible benefits of adding vitamin D supplementation to hepatitis B patients undergoing Peginterferon, or treatment with nucleotide analogs.
While researching this blog, I ran across a couple references that mention Fanconi’s Syndrome and vitamin D.  This is interesting since Fanconi’s Syndrome may be acquired as a result of HBV treatment with tenofovir.  Fanconi’s Syndrome and supplementation with vitamin D is also mentioned on the Mayo Clinic site.  The problem is there are no studies that definitively discuss the benefits of vitamin D supplementation for those living with HBV.  I am no doctor, but there seems to be a connection between vitamin D and good liver health.
Start by talking to your doctor or liver specialist about the pros and cons of considering additional vitamin D in your diet. Request that your vitamin D levels be tested so you get a snapshot of your current levels. I had my girls’ levels checked.  They were adequate, but I regretted having them tested during the summer break when they are outside more often. I wonder how this reflects on their levels in the winter when they are rarely outside?  Food for thought.
The 25-hydroxyvitamin D (25(OH) D) blood test is used to measure serum levels of vitamin D. Normal serum levels, indicated by the Institute of Medicine (NIH), are 50 nmol/L (20 ng/mL) or greater.  Low levels are under 30 nmol/L (12 ng/mL).  See detailed chartsfor age specific requirements. There are all kinds of reasons for inadequate levels of vitamin D, so it is important to follow up with your doctor if your results are out of the normal range.  You may require additional testing.
It is important to maintain a balance and use common sense when considering supplementing your diet with Vitamin D.  Vitamin D is essential, but too much of a good thing can be dangerous to your health. Be sure to keep your doctor in the loop – especially if you are currently undergoing HBV treatment.
Check out Thursday’s blog for those looking for vitamin D details and sources.
                                                                                       
                                                                                        This entry was posted in Adults, Blood Tests, General Hep B info, Hep B Treatment, Living with Hep B, Pediatrics, Research and tagged fatty liver disease, HBV, Hepatitis B, NAFLD, vitamin D. Bookmark the permalink.                                                                                       

上海人

l四蹄先生，中文啥意思？

StephenW

回复 上海人 的帖子

一些医生认为维生素D对B型肝炎病人有好处。
在以色列，他们临床试验维生素D+干扰素.