Give Me A Head With Hair, Long Beautiful Hair…

Among the plethora of side effects of Hepatitis Treatment that are listed in all the Study documents and online resource sites, nowhere does it mention that undergoing Hep C treatment will turn you into a cat. I realize this may require a bit of explanation so here is the back-story, as the theater folks say.

I have long hair. I have had long hair since my twenties. In fact, it has been about 35 years since I have done more that trim the length of my ponytail every several months and keep my beard trimmed. In years past (as little as 10 years ago), much of my hair was dark brown. It was also present in a reasonable quantity. Sure, there were areas where it was clear that my scalp was encroaching into areas previous covered with hair, but overall, I was doing better than any of the men in my family had ever done before. Over those ten years it has gradually gone increasingly gray; to the point that before treatment started I was more gray than brown.

Then interferon began to exert is magic. First my hair began to turn increasingly white. It is not completely white yet (that would be James Coburn cool), but the strands of gray and brown seem to getting mighty few and far between. Then it began to slowly up and leave my head. It does not fall out in huge clumps as is the case with other forms of Chemotherapy. It just gradually gives up the ghost, hair by hair, and slips away. I track its disappearance by my elastic ponytail band. When I started treatment, I needed three loops of the band to hold my hair securely. Now, when I brush my hair in the morning, I have to loop the band 5 (Five!) times around the few remaining hairs in my ponytail to hold them firmly in its grasp. In fact it’s not really accurate to call it a ponytail anymore, it’s more of a pony strand.

Where does all this hair go? That is where the catlike nature of the situation lies. Any chair that I use regularly – those at work for example - becomes gradually covered with a layer of long gray hairs. The sofa at home, the chair on the back porch, even my pillow, all slowly receive a coating of long gray hair. It is not long enough to be my wife’s and besides, she is clearly not losing any hair. It is mine, or more accurately was mine. My jackets and coats as well all testify to the fact that I am shedding, more rapidly as time goes on, what is left of my hair. To be genteel about the situation, I find it most distressing. To be more straightforward, it sucks.

Everyone involved with the treatment and with our support group tells me it will grow back, but that is cold comfort. Cold being an operative term as the lack of hair definitely points up that it had been keeping my head warm all those years. There are far more serious issues involved with hepatitis C and its treatment, but this one just strikes a nerve. While I like cats, I don’t want to shed my coat until I become a large pink hairless version.

The only thing that saves me now is that my hair is light, my scalp is white and it seems there is more hair than really exists. How much more time I can buy with that before it’s time for the shaved head well, I’ll keep you informed.

Research Leverage – Use It or Lose It

In the previous post, I discussed at some length the reasons Research Drug Trials are often harder on the patient than Standard of Care (SOC) treatment through you doctor. I also talked about the advantages of being in a research trial not the least of which is the access to new drugs that can increase the chances for successful treatment. There is another aspect of being in a research trial that you can use to help you mitigate the side effects and stress of being in a drug trial, it is the leverage you have regarding the data they are collecting from you body.

Once they move beyond the Phase 1 trials to determine basic efficacy and safety, research trials increase in size and length. The reason is that to determine the effectiveness and side effects of the drugs under study, they need a large enough sample to give them statistical significance. Therefore they recruit hundreds of subjects for the trials. There is another reason for recruiting larger numbers of subjects. The researchers know that a certain number of the patients entering their trial will not finish it. Some will fail to abide by the parameters of the study. Others will consistently miss taking doses of their drugs and be dropped from the study. Still others will have such severe reactions to the drugs that they will not be allowed to continue. There are those who will leave the area and not be moving to a location that has the necessary facilities to allow them to continue and some will just not be able to stay the course for the necessary time to complete the study. So they need to recruit enough people to collect enough data even after the inevitable attrition of subjects.

This is where your leverage comes in. The researchers want your data, they need your data and they need you to complete the trial for that data to become a useful part of their records, reports and papers. Therefore they will go to some lengths to keep you in the study. If you move, they will try to find a lab or medical facility near you that can continue the testing they need for the trial. They will work hard to educate you about what you have to do as far as dosing and record keeping and keep at you to do it correctly. They will also prescribe remedies for some of the side effects to make it possible for you to stay in the trial.

That is why it is important to report side effects to the researchers as they happen. It is also important to tell them how severe they are. If they are interfering with your ability to function effectively tell the researchers that as well. For some of the side effects, they will adjust you research drug dose to attempt to mitigate the situation, for others they will prescribe medications to ease the side effects. It is not necessary to exaggerate any of the information you are giving them. Be factual, but above all be timely. If you report accurately and quickly when you have side effects and when those side effects are becoming a real detriment to your life, they will do what they can to help because they want your data. To get your data, they need you in the study. That is your leverage and if you don’t use it, you lose the advantages it can bring.

To use my case as an example, if I had reported the muscle pain in my sides that the interferon causes as soon as it happened, they would have prescribed Tramadol sooner. I would have been more comfortable and probably better rested earlier in the study than I was simply by reporting the severity of the situation as soon as it was happening. Likewise with the insomnia that is a common side effect. I was sleeping badly for a few weeks before the truly enormous bags and dark circles under my eyes made it plain that I was not getting enough sleep. When it became obvious they moved quickly to prescribe the Trazadone to help me sleep. The same was true with the depression caused by the interferon. If I had been reporting my mental state more accurately, it would have been apparently several weeks earlier that I need help for my mental state. As soon as it was plain that I did, they started on the search for the correct antidepressant.

So even though, they want to watch the progression and severity of the effects and side effects of the drugs and they want to control the variables of drug interactions by keeping what you are taking to a minimum, they also want you to complete the study and get your data. Use that leverage to help make your own treatment as bearable as possible.

Why Research Trials put the P in Pain, the F in Fatigue and the M in Mental Breakdown.

The pitfall of participating in a research drug trial for Hepatitis C is that it will tax your mind and body more harshly than if you underwent the standard treatment or Standard of Care. The upside of participating in the trial is that you get a chance to take a drug that improves (sometimes drastically) you chance of clearing the virus. In order to do the research necessary and gather the data needed for the study, the subjects of the research are required to enter the study “naked” or without the support of drugs and supplements that can help mitigate the side effects of the anti-Hep C medications, at least until the study doctors decide to administer any such mitigating therapies. (The word “naked” refers to a baseball term reported by Hall of Famer Tony Gwynn of the San Diego Padres. He stated that during his time in the Major Leagues players who took the field without using amphetamines were said to be “playing naked”).

What this means in practical terms is that the subjects of a research study will experience all the side effects of the anti-Hep C medications without the benefits of many of the established remedies that patients who undergo the Standard of Care of Pegylated Interferon and Ribavirin can take advantage of from the very beginning of the study.

Pegylated Interferon is well known to cause depression, fatigue, brain fog, nausea, insomnia and depressed white blood cell counts. Patients undergoing SOC through their doctors are often prescribed antidepressants before the start of the study in order to combat the depression. They are routinely prescribed anti-nausea medications and sleep aids from very early in their treatment to deal with those particular side effects as well. Ribavirin is well known to cause anemia (often severe), itchy rash, nausea and muscle pain. SOC patients are prescribed drugs to combat the anemia, given anti-itch creams (often with steroids), anti-nausea meds and painkillers for muscle and joint pain. These are usually given as the symptoms are reported and continue for the length of the treatment. This is not exactly the case with the subjects of a research study and there are very good reasons for that.

As I discussed in this post, the effectiveness of the Hep C drugs and the results of drug interactions are complex things to parse. Combine that with trying to track the side effects caused by the study drugs and you need to control as many of the variables as you can for an effective study. To that end during the screening process for the study, the study doctors want to know every drug and supplement you are taking. If any of them would interfere with their ability to determine the effects of the study medications, they will ask you to stop taking them or, if you cannot stop taking them for medical or other reasons, they may disqualify you from participating.

The same need for a controlled medical environment applies once the study begins. The researchers need to track the efficacy of the treatment drugs and the number and severity of the side effects. To do this, you need to experience the effect of the drugs and the side effects of the drugs without the interfering effects of other treatments and if there are other compounds you are taking, they need to be able to track their use.

So you are going to experience the side effects in full force. It is when the side effects are either dangerous or interfere with your ability to continue with the study that you may be prescribed something to help you deal with them. To use my case as an example, I have not and will not be prescribed anything to deal with the anemia caused by the Ribavirin. This is because they want to track as clearly as possible whether this new combination of drugs changes the instances and severity of the anemia. Many other individuals I have talked with about their treatment experience were given drugs to stimulate red blood cell production. Rather than do that the researchers have adjusted my Ribavirin dose to try to keep my hemoglobin count above the minimum they require to continue the trial. I have not been given anything to help with my white blood cell counts but have had my interferon dose adjusted and even skipped to attempt to keep my neutrophil and lymphocyte counts above the minimum to continue the trial. When I began to report muscle pain associated with treatment, I was told to take over the counter medications. It was only when I reported that the pain acute enough to interfere with my sleep, that I was prescribed a painkiller.

Interruption of your normal sleep patterns is one area that they respond to fairly rapidly. The researchers believe that getting enough sleep is vital to your ability to be able to complete the study. They want to hear if you are having difficulty sleeping and they want to be the ones to determine what remedy, be it over the counter or prescription you are going to take to combat the problem. It is a matter of controlling the variables again. In my case, about 6 weeks after the had prescribed the pain med Tramadol to deal with the pain that was keeping me awake I reported that I was having difficulty getting any more than 4-5 hours of sleep per night. They immediately prescribed Trazadone to help me sleep.

Depression is another major side effect that gets handled differently in a study. Unless a patient was already taking an antidepressant previous to screening for the study, they generally do not prescribe them until the researchers believe they are necessary to your ability to complete the study. Those of us undergoing the study in San Francisco were all given information on strategies to handle the stresses of the treatment and programs to give support to Hep C sufferers, but we were not prescribed anything for the condition until they were convinced we needed it. In my case it was about 18 weeks into the study before AVB began to believe I needed to be given something. By that time, it took me three weeks to gather my thoughts and energy enough to realize I was beginning to tip over into serious depression. At that point, they moved fast and started me on SSRI antidepressant drugs.

All these discussions and examples are provided to make sure you think about this aspect of a research study. I did not consider it at all. It was not until I had been in treatment for a few months that I went to a support group and talked to people who had undergone the standard treatment, that I found out that they were routinely prescribed things to deal with side effects. It was then that it hit me that as lab rats for Roche, we were going “naked” in the study. I have a bit of background in science and my wife has “A Masters Degree In Science,” as Doctor Science used to say. We both realize that controlling study variables is essential to getting good data and ending up with a useful study. I just didn’t think clearly at the beginning of the study, that I was the one whose variables were being controlled and that might mean the course of treatment might be a bit rougher than the SOC.

Knowing what I know now, I would not choose differently. In my mind, the chance to take a drug that increases my chances of clearing Hepatitis C genotype 1a by 50% is worth the potential of having a harder time in treatment. I wish I had thought it through and prepared myself mentally for the realities of what that would mean, but I would not change my decision.

Your decision is up to you. Think it through; be aware of what entering a research study means and then with the most forethought you can, make up your mind.

New Morning & Another Reason for Keeping Notes

It is very clear to me now both why doctors prescribe antidepressants and why patients endure the early symptoms until their brain chemistry stabilizes and the drug begins to work. I feel…better. It is a curious state to attempt to describe. As my friend BS says, “You generally don’t notice feeling okay or good, but you do notice when you feel bad.” There is also the fact that as you experience a particular state for an extended period of time, be it either feeling good or feeling blah, you come to take it as your normal state and forget that you used to feel differently.

In my case, I realize now that the treatment regimen had gradually been grinding down my mental energy and state of mind. I had not noticed it as it happened though the folks running the study, and AVB in particular, claimed that they could see it happening to me. They actually had the advantage of seeing me intermittently as opposed to every day. This allowed them to notice the changes more clearly because they showed up as significant differences. It’s like the first time you spend some serious time away from home. When you return you notice real changes in your parents and siblings that would not have been nearly so obvious had you been with them on a daily basis. Likewise with me, my wife and I were immersed every day in the grind of treatment and thus the incremental changes became what were normal as opposed to something we should be paying attention to. If nothing else, the declining number of posts per month to this blog should have been a tip-off that the depression and why-bother attitude induced by the interferon were taking a very real toll.

Now that I have been taking antidressants for about 3 weeks and Celexa in particular for about 10 days, I feel a bit better; a touch more mentally alert; less likely to have the why-bother attitude. I still get tired and lose the ability to concentrate by early afternoon, but now when I get home, I don’t just drop onto the sofa and watch a couple hours of awful television in a kind of passive stupor. I still turn on the TV, but I now get bored after a while and find something else to do. The ability to be bored by stupid, mindless crap is a great gift of mental achievement that has been returned to me by modern bio-medical research and I am grateful.

This is yet another reason to keep notes about yourself while you are in treatment. If I had done nothing more than record the number of hours I was watching television, it might have tipped me off that my mental outlook was going downhill. So take notes, date them and look them over from time to time as treatment goes on. You have to review them regularly because the interferon is going to fog your brain and ruin your memory during treatment. If you do these things, you can stay ahead of the side effects and do your doctors a great service by having good information to give them. Both of these things will help you come through you treatment more successfully.

PS: A purely personal note about Celexa because it means a lot, SEX IS BACK!

Back on the Interferon Bandwagon

After a reduced dose of Pegasys two weeks ago and a skipped dose last week, I am back under the hammer, so to speak. The dose reduction was due to my neutrophils being below 500. The study doctors believed my neutrophils would rebound without the interferon pounding down the white blood cells. They were right. The number popped up to 1250 and they put me back on a half dose of Pegasys.

It is amazing how much you can forget in 20 days. While I had a lot going on the past few weeks what with the acclimatization side effects of the antidepressants and the new drugs I was taking because of it, nonetheless the number of interferon related physical symptoms that disappeared without my noting their passing surprises me.

I injected Thursday evening and that night I had night sweats and had to change my t-shirt twice. By Friday late morning/early afternoon I had the mild headache and general crappy feeling in the head that you feel when you are coming down with something. By 5:00 p.m. my muscles started to ache, especially in the butt area (How can you mindlessly watch TV while feeling crappy and sore if you butt is aching?). That night I had a generally stuffy head and by Saturday morning the middle of my back was stiff and cramping. I had my first wave of nausea around noon and I also had a sore spot in my breast but with my general clumsiness of late, it could easily be the result of my running into a door, or wall, or chair, you get the idea.

All of these symptoms had disappeared over the past 20 days. Their disappearance was accompanied by completely forgetting about them. I didn’t really even register the fact that I hadn’t felt nauseous in almost three weeks. That would seem to be the sort of thing that you might take note of.

I think this points up the importance of keeping notes about your general health, side effects and mental state throughout your treatment. It doesn’t have to be elaborate. Just a small notebook wherein you note how you are feeling generally and any unusual or unique effects you are feeling. It really helps to be able to flip through you notes and realize that a particular symptom or side effect or your general state of health and feeling is something that you have experienced before. The interferon really affects your concentration and memory and it is very easy to completely forget about something earlier in the treatment cycle that seemed it would be unforgettable at the time. So make notes and keep records. A little notebook of the history of your treatment can be a great friend to you when something seems to be coming out of nowhere, but actually happened to you in the past.

Complexity, Thy Name Is Drug Interactions

I do not envy medical researchers their jobs. While puzzling out the secrets of biochemical reactions and how they can be used to counteract the malign effects of viruses, bacteria, cancerous cells and the effects of defective genes must be fascinating and rewarding work, sorting out the effects and side effects seems dauntingly complex.

To use my case as an example, initially I was taking 3 drugs to attack the Hepatitis C virus. The interferon (Pegasys) and Ribavirin (Copegus) were well known drugs; indeed they are the Standard of Care or SOC, with well-documented effects and side effects. Those effects, however, all vary with the individual receiving treatment. For some, they have little effect on the Hep C virus, for others they are tremendously effective. Some individuals are devastated by the side effects, even to the point of being unable to complete the treatment, others individuals have a relatively straightforward time of it with a few difficult side effects but none that are debilitating. To this well-known set of circumstances they added a new drug, the polymerase inhibitor RO5024048 aka RG7128. Phase 1 testing had already been done using the new drug alone and its side effects noted, but aside from a worrying potential effect on the kidneys, many of the side effects mimicked those of the SOC. So as the study progresses and the effects and side effects are tracked and cataloged, it becomes vastly more complex to attempt to determine which drug might be doing what; what synergistic effects might be occurring between drugs; and what other effects might be the just the degree of effect of each drug on the specific individual undergoing treatment.

As the treatment progresses the Ribavirin wipes out your hemoglobin and gives you anemia and potentially itchy rashes. The interferon wipes out your white blood cells, saps your energy, fogs your brain, tends to give you depression and robs you of the ability to sleep well if at all. So to counteract these effects, additional drugs are prescribed. To continue the example of my case, I am currently taking 4 additional drugs. Firstly, I was given Tramadol (Ultram) to counteract the fact that as part of my interferon cycle, the muscles along the sides of my body can be achy and painful enough to leave me unable to lie down. As you might imagine this makes it difficult to sleep. Next, as the general insomnia caused by the interferon kicked in, I was given Trazadone to use as a sedative. Then, as the interferon gradually eroded my natural good cheer (okay my occasional good cheer) they prescribed an antidepressant, Paxil. In order to bridge the time it took for the Paxil to reach full effect, they added Ativan to the witches’ brew of drugs. The side effects of the Paxil necessitated a switch to another antidepressant, Celexa, but the total result is still the same. I am taking 4 additional drugs to counteract the effects of the drugs I am taking for the Hep C.

A final complication during the trial is changing dosing of drugs. In this trial, we only took the experimental polymerase inhibitor for either 8 or 12 weeks and potentially (depending on which arm of the trial you were in) at three different strengths. So after the first 12 weeks of the trial we were all down to 2 anti-Hep C drugs. There is also dose-adjusting going on for those two drugs as well. I have administered full, half and ¾ doses of interferon and even been told to skip a dose at various times during the study depending on my various white blood cell counts. I have been reduced to a lower level of Ribavirin to attempt to counteract my anemia. These sorts of adjustments are the norm for various patients throughout the course of the study.

To all this you can add the complicating effects of human foolishness, forgetfulness and folly (I should have written sports headlines). Again, we have the convenient example of my own case as an illustration. The context for this particular case of foolish forgetfulness comes from two previous posts. In one, I detailed all the benefits of The Everything Tastes Like Crap Diet, in the other I mentioned that chocolate had some very powerful effects on me after I started treatment. Well, the third day after I started the Paxil, while still in the speed rush phase of the acclimation period, I began to actually fell hungry again. I don’t know if it was the psychological effects of the Paxil or just because my body was using so many calories it was crying for food, but I went to the store with a real desire to buy food. I also noticed that foods I had not though appealing in weeks or months began to seem like they would be really good. The though of eating ice cream occurred to me for the first time in months, particularly chocolate ice cream. So I bought a pint of chocolate ice cream and went home and ate it in one sitting. The next day I did it again, and the next. All this time I was noticing that I was jittery and had a great deal of nervous energy. The jitteriness was moderating as the days went by (as I acclimated to the Paxil I thought), but did it occur to me that the effects of the massive doses of chocolate might be contributing to this? Heck no, never crossed my mind. By the way, despite the massive influx of delicious fat into my body, I still continued to lose weight.

Due to side effects that I believe are completely unrelated to any chocolate consumption (chocolate is supposed to increase libido, I believe), they switched me to Celexa. About 4 days in to the Celexa regimen, I once again noticed that I was a bit jittery and nervous. Finally it occurred to me that I had been eating a lot of chocolate. That same day, as I bought my pint of ice cream on the way home from work, I bought vanilla and have ever since. I haven’t noticed a huge difference, though I continue to be less jittery and nervous every day, but there is one more piece of evidence that I just can’t ignore.

I was at work today and I got a bit hungry around 11:00 a.m. I went down to the lunchroom and among the volunteer snax there was a bowl what I thought was trail mix but turned out to be pure M&Ms. I took a small cup of them went back up to my lair and proceeded to nibble on them as I prepped eBay auctions. About 15 minutes later I noticed I was a lot more wired than I had been before. It was not just a sugar rush, it was the jitters, case closed.

So, not only do the researchers have to deal with the seemingly endless complications of drug to disease interactions, drug to drug interactions and drug to human interactions, they also have the wild card of patients who can’t even keep track of their own food reactions. And these reactions are the ones the researchers are never even aware exist. Good luck to all of them, because we patients aren’t always reliable reporters.

I blame it all on the brain fog…

Round and Round the Drug Carousel.

It’s been a few more days and the antidepresseant cycle has modified into a steady spaced out condition. It has the sort of charectaristics I mentioned in the past post be without much nervous energy, or any energy at all for that matter. It’s sort of a passive, pleasant, unconcerned state of mind. I have no real idea if that is the intent of using antidressants in the context of a chemotherapy regimen, but that is where we are.

My weight has stabilized, but the sexual dysfunction persists. I don’t really have the interest to even attempt it anymore. That fact that it doesn’t bother me creeps me out.

I went in today for yet another redraw to check neutrophil and lymphocyte counts. They were low enough last week that I was told to skip my interferon dose. They hope that the interruption of the interferon dose with allow a bounce back of my white cell counts and allow me to resume the interferon with the next dose.

After the blood work, AVB quizzed me at length again about my reactions to the Paxil, whether the Ativan had helped with the symptoms and how I generally felt about being on the Paxil. I told her about the powerful initial side effects and the time it took for them to call down. I mentioned that I was now in a state of steady unconcern with a side order of being spaced out and out of focus. I also told her that I thought that Doctor NB could do a great favor for future patients by spending some time to go over the more likely side effects and the periods of time that they might expect them to last. AVB asked whether the pharmacist went over the side effects and I informed her that at my inner city pharmacy, their was never much in the way of consultation.

I also went over the sexual side effects. She was quite concerned and put in a call to Doctor NB for a consult. As she said, the treatment is hard enough to deal with without removing your enjoyment of a basic component of living. She also mentioned that sex is one of the ways for couples to feel close to each other and offer support and during treatment, you need that more than ever.

It took about 25 minutes for Doctor B to arrive and the fact that I sat calmly and stared out the window without a care in the world for most of that time speaks to the spaceyness I was feeling.

When she arrived, Doctor B apologized to me for not spending the necessary time on side effects the last time we talked. She stated that they often left that to the pharmacists but that was not really acceptable. It was gracious and heartfelt of her and I appreciated it. After hearing about the sexual issues, she decided to switch me to another antidepressant. This one is also an SSRI, but is a different drug. It has a much smaller incidence of negative impact on sexual functioning. She went over the expected side effects (hooray!) and sent me out the door with a prescription for Celexa. She told me to hold on to the Paxil because you never know.


After Doctor B left, AVG talked about the many and varied forms of antidepressants. She said that someone like myself who is a virgin to those types of drugs is much harder to prescribe. Many people come into treatment with a history of antidrepressant use due to the side effects of Hep C and thus already know that Welbutrin works, but Zoloft, Prozac and Celexa do not for example. It may take even another drug before we settle on the best fit for me.

So once again, I am armed and dangerous with celexa in my holster and heading for a showdown with my other drugs, or something.