Anybody have a miracle stuck in their back pocket?

[susan400]

I have been feeling sort of down because of the prospects for me clearing this virus are dwindling up.  Yes, I know, that I'm far from hopeless and that there's still time, and blah, blah, blah.   But, I've basically been told that I can't do any of the protease inhibitors.  I was thinking about trying to get into the Boceprevir trials, but I've been told, flat out, nobody will take me into a protease inhibitor trial because of my having been exposed to the Telaprevir in the Prove 3.  I'm like, 'Oh terrific, so I'm like scr*wed?'   Schering has told me this, the former trial nurse at my last study site has told me this.  Whenever I inquire about the possibility of any other non-responder trials, nobody has anything available to me.  I suppose that there is always hope that eventually there will be a polymerase non-responder trial, but whether or not that they will take me, is debatable.  Waiting for a couple of years for one of these new drugs to be FDA approved really doesn't help me much because I have no prescription drug insurance, so I wouldn't be able to pay for them.  So, I'm left with, do I just hope and pray that I progress none?  Since I've had bridging fibrosis for 7 years, is that even likely?  I am praying for a miracle because nothing I have tried has worked.  I'm not trying to make anybody feel bad, or to just be a negative old grouch, but I'm really feeling down about this.  I don't understand why I have been unable to clear!  

Susan400

[nygirl7]

"It seems crucial to have some response to interferon in order to get well no matter what mixture your using"


Actually Susan had a great response to the intereferon/telepravir treatment but just didn't have the riba to go along with it.....how they could do that to a multiple treater as many times as she was I don't understand - even in blind studies that is just NOT fair.

Anyway I'm going to email her and tell her the thread is still going - I don't know if she knows or not.

[Proactive]

I'm about filled up with medhelp for awhile, but I did want to ask you, you mentioned you had been turned down for the Boceprevir trials, but have you checked into the Schering 2nd gen PI SCH 900518 trials? This drug looks very promising. I admit I've fallen out of the loop of trials and studies, so I appologize if you've discussed this one already..It is my belief we will see second gen pi's come through fda approval process faster than gen 1..but we will see...
You're a tropper Susan, and something will come your way!!
Pro
PS: I seem to see different trial stats--this one is for treatment naive
http://clinicaltrials.gov/ct2/show/NCT00797745?cond=%22Hepatitis+C%2C+Chronic%22

Yet from a pr on the next-1 study, there does seem to be reference to "those who failed prior treatment"
"Next-Generation HCV Protease Inhibitor SCH 900518

As part of its long-term commitment to hepatitis C therapy, Schering-Plough also is developing SCH 900518 ("518"), a next-generation HCV protease inhibitor. A Phase IIa study with 518, known as the NEXT-1 study, is currently ongoing. The company said that 518 has been shown to be 10 times more potent in-vitro than other protease inhibitors currently in Phase III development and has the potential for once daily dosing. 518 also has shown decreased emergence of resistance in vitro. Given its pharmacokinetic (PK) profile, the company anticipates that 518 may be active against some HCV strains that are resistant to other protease inhibitors. Phase I proof of concept studies with 518 in treatment-naive patients and those who failed prior treatment, both as monotherapy and in combination with peginterferon (without ribavirin), demonstrated enhanced antiviral activity, with up to 4 log10 and 5 log10 decreases in circulating HCV, respectively.

Full results of the boceprevir HCV SPRINT-1 study and early phase clinical results with SCH 900518 are being submitted for presentation at a future medical meeting."



"

[Rockerforlife]

THIS NEW PI DRUG IS 10 TIMES MORE POTENT THAN WAHT IM DOING

[Rockerforlife]

http://www.medicalnewstoday.com/articles/130622.php

[Marcia2202]

This is what Rocker posted on one of his threads. Thought it might interest you.

Next-Generation HCV Protease Inhibitor SCH 900518

Article Date: 25 Nov 2008




As part of its long-term commitment to hepatitis C therapy, Schering-Plough also is developing SCH 900518 ("518"), a next-generation HCV protease inhibitor. A Phase IIa study with 518, known as the NEXT-1 study, is currently ongoing. The company said that 518 has been shown to be 10 times more potent in-vitro than other protease inhibitors currently in Phase III development and has the potential for once daily dosing. 518 also has shown decreased emergence of resistance in vitro. Given its pharmacokinetic (PK) profile, the company anticipates that 518 may be active against some HCV strains that are resistant to other protease inhibitors. Phase I proof of concept studies with 518 in treatment-naive patients and those who failed prior treatment, both as monotherapy and in combination with peginterferon (without ribavirin), demonstrated enhanced antiviral activity, with up to 4 log10 and 5 log10 decreases in circulating HCV, respectively

[Marcia2202]

I'm bumping this up for Rocker, as he posted some new PI info on another thread, which sounds like hope

[dointime]

New Study – 3 Antivirals, No Interferon:

Roche, InterMune, Inc, and Pharmasset jointly announced on November 10 a new study called INFORM-1 to evaluate the safety and antiviral activity of three antivirals – R7227 (ITMN-191) an HCV protease inhibitor, R7128 an HCV polymerase inhibitor and ribavirin.

This will be the first clinical trial combining three antiviral medications without the use of interferon as a possible treatment of hepatitis C.    

The study will evaluate the three antiviral medications in HCV genotype 1 treatment-naïve patients.  The clinical study will be conducted in Australia and New Zealand.  Hopefully, this first of its kind study for treating hepatitis C will usher in a new era that will include many combinations of antivirals to treat hepatitis C, and which may ultimately lead to therapies that do not contain interferon or ribavirin.

[dointime]

"It seems crucial to have some response to interferon in order to get well no matter what mixture your using"

Actually this is not necessarily true for the future, although it is propbably true for the next few years.  There is debate going on that it might be enough to reach SVR if it were possible to just stop viral replication 100% for enough time.  This should eventually become possible with a mixture of antivirals such as is used for HIV, or maybe a microRNA, without either interferon or ribavirin.

I don't want to give anybody false hope here as this option is probably about 10 years down the road, but I'm just trying to keep the door open for interferon non-responders.

I do agree that everybody should be checked for insulin resistance just in case as that does seem to play quite a large role in non-response.  Comeagain, do you think you could get the test done elsewhere?  

Just for the record, Susan I think you are a partial responder seeing as you do get a reduction in your VL, just not all the way to UND.  So if I were you I'd wait for 2 potent direct antivirals to become available, add alinia and double dose peginf. with the normal riba - and rescue drugs if needed.  I reckon that lot will kick viral @ss for you.

Dointime
        

[comeagain]

I think we all must try to remember when talking about new meds polymerase protease inhibitors etc. non of this work without soc and not everyone gets SVR on them and soc either.

It seems crucial to have some response to interferon in order to get well no matter what mixture your using

And since you have tryed so many times whether you gonna try polymeras in future or not, my guts tells me this IR question is real important for everyone that is about to treat on new drugs or  just soc and especially for us relapsers.

And we must realise that its not that few persons that have had a relapse and in my opinion  to go through with this tx even if it was 100% SVR  warrrantie is tuff as hell for a lot of us anyhow , and then knowing its a big chance you wont even make it.

Still go through with it, is  in my opinion the ultimate tribulation, thats why Susan what you have done is for me almust unbelievable, maybe its only Andiamo and a few others who have a clue to what youvé been facing , but i´m sure everyone with a heart in their body wants you to clear .

And to get your docs to do this does not seem easy I asked my NP to ask my doc if he could run such a test for me ( see if I was IR) , and his answer to that was its only fat people that needs to do that.

ca

[meki]

I don't have a miracle---- but I do have HOPE --- and a HUGE HUG!

HUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUGGGGGGGGGGGG!!!!!!!!!


Love you!

Meki

[CoWriter]

"Off of treatment it's been running around 105 to 111, but no higher."  

"Since I'm not considered diabetic by my doctor, I really don't think that he'd put me on diabetic Type II sort of medicines."
-----------------------------

Let me explain something to you.....

What DECREASES INSULIN RESISTANCE???

1.  Exercise.
2.  Gradual weight loss if you're obese. (quick weight loss can cause insulin resistance)
3.  Getting rid of the Hepatitis C virus.
4.  Medications like Metformin, Avandia and Actos

(Sometimes weight and exercise alone are not enough to decrease insulin resistance because the Hep C virus keeps causing it)

Medications like Metformin (or Avandia) decrease insulin resistance......they're "insulin sensitizers".  In other words, they help make the cells in your body more sensitive to insulin. BUT they DO NOT make the pancreas produce more insulin, so they won't make your blood sugar come down 20 points of whatever.  They don't do that.

On the other hand, medications like Glyburide or Glipizide (called sulfanylureas) stimulate the pancreas to produce more insulin.  That's the kind of medications that will make your blood sugar come down.  When you take that kind of medication, you are told to always carry sugar with you in case your blood sugar goes down too low.

When you use Metformin you don't have to carry sugar with you because it will NOT  cause your sugar to go down too low.  


Let me explain to you what Metformin and Avandia do....

When you eat a meal, the food goes from the mouth to the stomach where it turns into liquid sugar. From the stomach and intestines, the sugar is quickly absorbed into the blood.

****Metformin helps by making the sugar slow down a little so it's not absorbed into the blood so fast.


When the sugar goes inside the muscle cells....the muscles use the sugar as energy.

****Metformin helps the muscles use the sugar a little faster.


During the night, the liver gives you a bunch of sugar.  (This is the biggest problem for anybody with Hepatitis C.  The Hep C virus causes large amounts of sugar to be disgorged from the liver).

****Metformin tells the liver not to give you so much.


So Metformin helps....but it doesn't make the pancreas produce more insulin. So it's not going to make the blood sugar come down 50 or 60 points. It doesn't do that.

Think of it this way......

If insulin is like keys....and some of those keys get rusty and don't work.....then Metformin is like oil you put on the key holes so the keys work better.

And if you can do that....if you can decrease the insulin resistance, then your chances of SVR with SOC will increase.

Because starting treatment with a fasting blood sugar of 105-111 is like defeating yourself before you even start.  

You asked for an answer as to why you've failed tx so many times and CS gave it to you.  What you do with it is up to you.

It would be hard to convince your doctor...yes, I'm sure it would.

Co


Sources:

"Insulin-Resistance in Chronic Hepatitis C patients: New Predictor of Sustained Virological Response Independent of HCV Genotype and Liver Fibrosis Stage."

http://aasld.scientificposters.com/epsAbstract.cfm?id=37

"Insulin resistance and hepatitis C."

http://www.ncbi.nlm.nih.gov/pubmed/1713 ... d_RVDocSum

"Insulin Resistance and Hyperinsulinemia. Is hyperinsulinemia the cart or the horse? "

http://care.diabetesjournals.org/cgi/co ... type=HWCIT

"Hepatitis C and insulin resistance: steatosis, fibrosis and non-response."

http://scielo.isciii.es/scielo.php?pid= ... ci_arttext

"Incidence of type 2 diabetes mellitus and glucose abnormalities in patients with chronic hepatitis C infection by response to treatment: results of a cohort study."

http://www.ncbi.nlm.nih.gov/pubmed/1870 ... d_RVDocSum

"Hepatitis C virus infection enhances insulin resistance induced by visceral fat accumulation."

http://aasld.scientificposters.com/epsAbstract.cfm?id=6

"Steatosis, Insulin resistance, Iron overload, Fibrosis and Viral load as negative factors affecting Early (EVR) and Sustained (SVR) Virological Response in patients with Chronic Hepatitis C treated with peginterferon and ribavirin"

http://aasld.scientificposters.com/epsAbstract.cfm?id=36

"Therapies to Manage Insulin Resistance Improve Response to Interferon-based Therapy in Chronic Hepatitis C Patients."

http://www.hivandhepatitis.com/2008icr/aasld/docs/112108_a.html

"Viral Kinetic Response to 12 Week Treatment with Rosiglitazone (Avandia) in Chronic Hepatitis C, Genotype 1 Patients Who Are Previous Relapsers or Nonresponders to Pegylated Interferon and Ribavirin."

http://aasld.scientificposters.com/epsAbstract.cfm?id=3

"In Chronic Hepatitis C (HCV), Pretreatment with Thiazolidinediones (TZDs) or Metformin Decreases Insulin Resistance (IR) and HCV Viral Load and Increases Early Virologic Response (EVR)."

http://aasld.scientificposters.com/epsAbstract.cfm?id=5

[merryBe]

hey, this miracle just showed up in sweden, check it out:

http://www.medhelp.org/posts/show/699038

[willing]

epiphny makes a good point - whatever resistance you acquired to the ns3a-targeted PIs (which would affect both TV and BC ) should be completely irrelevant to the  ns5B-targeted PIs like r7128. Maybe not a reason to emigrate, but it's worth keeping an eye on openings in  the polymerase inhibitor trials.

[CockSparrow]

Susan - Off of treatment it's been running around 105 to 111, but no higher.
On treatment it's been considerably lower at around 80 or 90, all fasting of course.

Susan - Since I'm not considered diabetic by my doctor, I really don't think that he'd put me on diabetic Type II sort of medicines.

I know what you mean I am in the process of trying to talk my Doc into doing that very same thing.
What we can do is prove
That IR reduces response
That Hyperinsulinemia stops Interferon from working

Then we can show that some of the recent studies into reducing HOMA-IR show promising results.

As we are at risk of developing Diabetes over the next 5-10 years, we should be doing something about IR anyway. Why wait until we both get Diabetes before anything is done about it.
A little preventative medicine goes a long way.
Bear in mind Doctors are not used to thinking about glucose of 105-111 as abnormal. To them 120 is perfect. But this is not the case for someone with Hep C.
Especially when on treatment.

Susan - I do already exercise almost to the point of obsessively.  I've been doing 2 miles a day on the treadmill and yesterday on Thanksgiving, I walked 3 miles in the morning before the big meal and another mile in the afternoon after the meal.
I don't really know that there's much more that I can do besides that.

Now the treatment for Pre Diabetes or Insulin Resistance is a Healthy Diet and Exercise but this isn’t enough for us.
Its not preventing Diabetes we are after but improved Interferon Signaling
I have got my Glucose down to below 100 (just) by taking supps. ALA NAC Taurine Resveratrol Astragalus and Stevia all help lower glucose. If you also follow a low carb diet then we should be able to keep a lid on it for a while at least. But there is no way I would want to take these sups on Tx. Much prefer to take an Insulin Sensitiser.
Not sure how permanent the lowering is either.

Oxidative stress also needs to be dealt with with. It damages the mitochondria which means it also damages the Interferon Siganaling pathways. IR and Oxidative Stress get a bit circular as they both cause each other.

Susan - I wish that there was some way that I could pre-dose with the diabetic meds and then, try to do SOC again, but getting a doctor that would be willing to do that for me is another problem.

This is a case of you having to lead your Doctor into the direction you want to go.
If I get what I want then you can use me as an example. If I can get it, then why cant you type of thing. And I will be using that as part of my argument for Alinia.

Susan - They have pretty much giving me that standard line of  'we're not going to do anything until the new drugs are approved' or unless or until I could possibly be in a polymerase inhibitor trial.  
I am totally listening to what your saying, but just don't know how I'd get it done in practice.  

Make then feel guilty for you treating 10 times and them paying no attention to how well Interferon signaling is working. Prove to them that IR probably is the cause of your non response. Most importantly of all don’t take NO for an answer.

And be patient, don’t rush into it make sure you are Insulin Sensitive before you start.
There is enough evidence to say it has a real good chance of working, if we do it properly.

CS

[epiphiny]

Lol, yes, I did just read Melbourne and assumed it meant Melbourne, Australia!  Silly me!  

Well, you could immigrate to Oz as treatment for Hep C is free and you could get on a trial..

So sorry to confuse and give you false hope...

Epi.

[jdwithhcv]

Oz is Australia.  My guess is that ephininy read Melbourne, missed the Florida part and assumed you live in Melbourne Australia.

Hope you had a nice holiday.

[susan400]

What is Oz?   I live in Melbourne, FL..., is that Oz?

[spcecst2]

Susan, I skipped over responding to this post several times, I’d start typing and then stop, I feel so bad about your situation I couldn’t get the words right, I know after relapsing twice I started thinking why me, now that I made it on the third attempt, I’m still saying why me cause I made it!!!!!!!!!!!! I know one thing, “DON”T QUIT BELIEVING”, you will get there, my doc almost cut me off after the first relapse, I almost had to beg for the second round, and someone made it all fall into place for the third round, the doc had no faith that it could happen, when I went for my 6 month test order I was so down when I left, cause they were so sure it didn’t work, but it did!!!!!!!!!!!!!!! I can’t know how someone feels after failing seven times, but I know about staying positive, when it looks bad!!!!!!!!!!!!!!!!!! Maybe you can write some letters to some of these big trial doctors and see if they’d be willing to take on a patient who’s willing to go the distance!!!!!!!!!!!!!!! I don’t think I would have my success if I didn’t change my tx schedule, I just put together a plan “I” thought would work, thinking it was my last shot!!!! Keep the faith and don’t take “There’s nothing out there for you” for an answer if you want to fight!!!!!!!!!!!!!!! Much Luv to you!!!!!!!!!!!!!!!!!!!!!

[epiphiny]

Hey Susan,  I just noticed you live in Oz and I know that Pharmasset and Roche are running trials there and in NZ for the ploymerase inhibitor R7128.  I am not sure what stage they are at, or whether there are any that would be suitable for you, but it could be worth further investigation.  You could check out their website ***.pharmasset.com or check the clinical trials page.

I did a trial for it with them earlier this year and they were really helpful, and I have good results thus far.  Was a prev non-responder and went UND at week 4.  Still UND with another 19 weeks to go (48 in total).

Hope you can find something, all the best....

Epi.

[proud48]

I am so sorry the study will not work. You have been in my prayers and I will continue to pray for you. It is very hard not to be down. One thing you know is many people on this forum care for you. Stay hopeful and stay in touch. Many blessings to you and remember tx. meds are changing all the time. :)
proud48

[susan400]

Off of treatment it's been running around 105 to 111, but no higher.  On treatment it's been considerably lower at around 80 or 90, all fasting of course.  Since I'm not considered diabetic by my doctor, I really don't think that he'd put me on diabetic Type II sort of medicines.  I do already exercise almost to the point of obsessively.  I've been doing 2 miles a day on the treadmill and yesterday on Thanksgiving, I walked 3 miles in the morning before the big meal and another mile in the afternoon after the meal.  I don't really know that there's much more that I can do besides that.  I wish that there was some way that I could pre-dose with the diabetic meds and then, try to do SOC again, but getting a doctor that would be willing to do that for me is another problem.  They have pretty much giving me that standard line of  'we're not going to do anything until the new drugs are approved' or unless or until I could possibly be in a polymerase inhibitor trial.  I am totally listening to what your saying, but just don't know how I'd get it done in practice.  

Susan400

[CockSparrow]

You may want to check this out.

http://www.natap.org/2008/HCV/031008_01.htm

Glucose >100 mg/dl Reduces Interferon/RBV SVR
  
Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C

As has been reported previously with respect to insulin resistance, abnormal glucose values (>100mg/dl) have been shown in our study to be associated with a lower rate of SVR to treatment.

The question of whether intervention using oral hypoglycaemic drugs, or diet and exercise, improves the response rate in this group of patients warrants further exploration...

Your glucose is above 100. See the connection.

CS

[CockSparrow]

Keep forgetting this site hates greater than signs.
Here is the missing bits

Glucose tolerance is classified into three categories based on the FPG:
• Normal:  FPG Less than 5.6 mmol/l (100 mg/dl)
• IFG: FPG Greater than or =5.6 mmol/l (100 mg/dl) but <7.0 mmol/l (126 mg/dl)
• Diabetes: FPG Greater than mmol/l (126 mg/dl)

CS

[CockSparrow]

My blood sugar was slightly high, but not yet into a diabetic range.  My weight is normal.  

If your glucose is above 100 mg/dL which is only slightly high then it likely you are Insulin Resistant. If most of you Glucose levels have been around 100 then you are definately Insulin Resistant.

You dont have to be Diabetic to be Insulin Resistant.
Below is from the American Diabetes Association.
Its in regard to the risk of developing diabetes but you will get the idea

Glucose tolerance is classified into three categories based on the FPG:
• Normal:  FPG 5.6 mmol/l (100 mg/dl) but 7.0 mmol/l (126 mg/dl)

IFG is comparable to impaired glucose tolerance (IGT), which is defined as plasma glucose levels between 7.8 and 11.1 mmol/l (140 and 200 mg/dl) 2 h after a 75-g OGTT.
Individuals with IFG or IGT are at substantial risk for developing type 2 diabetes (a 40% risk over the next 5 years) and cardiovascular disease.

If you get you insulin tested you can then calculate your HOMA-IR score

CS