I’ve kept wondering what it’s like for someone with migraine to actually try these drugs. Elizabeth Roberts-Zibbel, who has chronic migraine, has kindly agreed to share her experience participating in studies. In a completed study for Amgen’s AMG233, Elizabeth had reduced pain levels and a noticeable improvement in her quality of life. The study included an open label phase, during which time she knows she received a low dose of the active drug. She was so impressed by the improvements that she’s participating in a second study, which just began.
Elizabeth’s responses are in two sections. The first is about the clinical trial experience in general and the second is about her experience with the medications themselves. While you may be most interested in her response to the drug, the first section provides context for understanding the dosing and administration of the drug.
On Participating in Clinical Trials
Kerrie: How did you learn about the trials?
Elizabeth: I was extremely lucky. I had always wondered about participating in a trial, but never had the impetus to investigate on my own. A childhood friend actually contacted me because she is a coordinating nurse at a research and treatment facility about an hour away. She had been reading my blog and Facebook posts, and even remembered that I had severe headaches in elementary school when we were friends, and felt inspired to reach out, believing the CGRP medications being developed would help me as they’d helped so many of the patients she was working with. Needless to say, I was ecstatic, and with her help I jumped on board immediately.
I am not going to name my friend or the facility where she works, but it is the home of a prominent migraine researcher whose name I immediately recognized.
K: When was the first study? How long did the double-blind phase last? How far into it before the open label phase?
E: I entered into the Phase 2 Amgen study in the fall of 2014. The double-blind part lasted 31 weeks: 6 weeks to establish a baseline, 12 weeks in which I received 3 treatments, and 13 weeks of monitoring after the treatments ended. The open label phase had separate consent forms and began immediately afterward.
K: Why did you decide to participate?
E: Like so many of us suffering from chronic migraine, I have tried every available preventative treatment (including six administrations of Botox) with little to no lasting success. I had been following the research about CGRP and was extremely eager to try the medications being developed. With the Amgen study, I was guaranteed to eventually receive the real drug, so I had little hesitation.
K: Were you concerned about safety? Do you feel like you took a risk participating in the study? If so, how were your concerns addressed?
E: I wasn’t concerned about safety, because this particular drug, known as AMG334, was in Phase 2 and there hadn’t been many side effects at all. I knew that there was some risk, but I was definitely okay with that due to my relatively low quality of life at the time.
K: Other than safety, what were your primary questions and concerns before the study?
E: I was definitely concerned about my ability to continue treating my nearly daily migraines. I knew I was going to be unable to take any sort of preventative medication during the study, which was detailed in the consent forms. (Interestingly, in this case supplements like magnesium, B2, and feverfew were included in that category, so I had to stop taking those as well.) My neurologist had most recently prescribed cyproheptadine (Periactin), and just like the first, second, and third times I had taken it I felt it was completely ineffective so I didn’t mind stopping. As far as acute treatment, I was worried that it could be determined mid-study that I was engaging in what would be considered by some to be medication overuse. Different doctors have different ideas about what constitutes overuse, so I wanted to be sure I knew the guidelines mandated by Amgen and the research doctor for the study so I didn’t inadvertently disqualify myself. I was given those guidelines, and I had to make sure I stayed within them, which was challenging, particularly since I didn’t have access to previous days’ data in the diary (it was used for daily data entry only). I had also been concerned that I might not be allowed to seek emergency treatment if a migraine became intractable, but I was assured that emergency treatment was permitted, I would just need to contact the study coordinator and let them know afterward.
K: What was it like when you went in for your injections? Did it feel like a normal visit to the doctor?
E: It did! Study coordinators at this facility have their own small offices with a desk, a few chairs, and an examination table. My vitals were taken before every treatment and I also had frequent blood draws (done in a lab on site). There were urinalysis tests, but not as many for me, because they didn’t need to check for pregnancy (since I had a hysterectomy in 2011). There were periodic allodynia tests, using a thin fiber almost like fishing line, and I also received frequent ECG tests of my heart.
The possibility of pregnancy would definitely be a consideration for many in determining whether to participate in a study. There were several pages of the consent forms dedicated to making sure pregnancy would not be a possibility. Not necessarily because CGRP medications are harmful to a fetus, but because they just haven’t looked at that yet and have no idea.
K: How did you keep track of how you were doing during the study? How often did you check in with the researchers?
E: During the studies, participants are each given a small mobile unit “diary” which is more like a Palm Pilot than a cell phone. The unit has a charger, an attached stylus, and a built-in reminder alarm. For the Amgen study, I was limited to the hours of 8 p.m. to midnight to answer a survey about my head pain that day, and then it would immediately be sent into my computerized file. The questions were extensive: aura, photo/phonophobia, nausea, when pain began and its severity, what medications were taken (at the beginning of the study the research coordinator enters which acute medications you personally use), and the impact as far as work, school, tasks. If I ever had any questions, I could contact the nurse/coordinator at any time. At first I drove up to the facility, just over an hour’s drive, every two weeks for testing, then it was every four weeks. I would always take the unit with me; it would be prompted to ask more involved survey questions at those visits.
K: What are the primary reasons you’ve decided to participate in a second study?
E: I was nervous all along that I would participate in the Amgen study and that when it was over, my life would return to the way it had been, and I would have gotten a taste of what it was like to be more “normal” and would then lose it. Once we knew that the open label phase was not going to be extended, my friend began to watch new and future studies for one I could participate in so as to continue receiving CGRP treatment and hopefully maintain my better quality of life. Fortunately, she was able to find one that I was able to enter almost immediately that allowed for participation in previous CGRP studies.
K: Do you know how the next study will be different from the first one? When will you start the next one?
E: While my participation is ongoing, the consent includes a non-disclosure agreement, so I can’t say which drug company is the sponsor of the second study. I did learn that even among the subcutaneously injected CGRP medications being developed there are big differences between mechanisms, so the dosages in this study do not apply to the dosages in the last study. Every participant is getting the real medicine, but varying amounts at varying frequencies. They are looking to see whether a very large “loading” dose is as effective over three months as smaller doses given every four weeks, for a treatment period of one year. Similar to the Amgen study, I began using the diary device at home in the weeks prior to my first treatment to establish a baseline. I prefer this device to the Amgen one, because it asks fewer questions each day and I am not limited to certain hours in which to enter the information.
My first treatment was in early July. The injections were more painful than those in the last study, which my friend said was consistent with other patients’ experiences. Each treatment will be three injections, and each month I will receive all three injections, though some (or all) may contain a placebo. Each had to be given in a different area, so we chose an arm and both thighs. The injection sites became blotchily red with a swollen raised area, reminiscent of my first uses of the Imitrex auto-injector in the early 1990s. The swellings were gone within a few hours with no remaining irritation.
I had a bad headache at the time of the treatment, and the medication almost immediately helped, but I had pain again after about six or eight hours. I ended up going to the ER because I’d had the migraine for around a week, and was unable to eat and stay hydrated. After successfully breaking that cycle, I felt the study drug was working in interesting ways. The other day, I felt like my head was “trying to hurt,” if that makes sense. Sort of like shadow pain that never fully developed, though I had other migraine symptoms and aura. It sort of feels like my brain is being cushioned; protected. I am very excited about this new study, because I think this medicine and dose may be more effective than what I was receiving during the Amgen study.
Elizabeth’s Experience With the CGRP Medications
K: For AMG33, how much of the drug did you receive—what was the dose, how often, etc.?
E: After my migraine baseline was established, I received three doses of either the drug or the placebo, one every four weeks, in October, November and December 2014. The double-blind aspect required there to be two subcutaneous injections each treatment. Even though the study is over, I still don’t know whether I was receiving AMG334 or placebo (I hope to find out eventually). Dosages weren’t discussed, though I know during the open label phase I was receiving what was considered a relatively small dose of 70 mg. The injections in this study were virtually painless, with no irritation at the site. They were injected into the same spot in my upper arm every time.
K: What was your life like during the first study?
E: It was far better than before the trial. I was able to be more active, which increased my quality of life and general happiness. I was able to spend more time with my daughters. The long drive to and from the study site was inconvenient but not unmanageable. The trials also change the way I feel about my illness in general, since I’m participating in the forefront of migraine research; I don’t have the sort of “dead end” feeling I began to have when I had to quit my job and apply for disability. I still worry about how things will be when the second study ends.
K: Did the drug in the first study reduce your migraine frequency, severity, and/or duration? How much in each area?
E: Even during the double-blind phase I would guess that severity and duration were decreased, and the migraines were easier to get rid of. When the open label phase began in March 2015 (three months after last double-blind treatment), I was getting a 70 mg subcutaneous injection every four weeks for approximately one year. During that time, there were some months I still had to answer survey questions daily in the diary, and some months I did not. I’m not sure I will ever be able to see my own specific results, but my experience during the study mattered to me more than quantitative data. And my activity continued to increase and my baseline mood was usually happy, as well, which I could not have said before the study began. I still was needing ER visits at about the same frequency, and was going through the same amounts of medication.
An interesting fact I should mention is that I had a rather bad migraine at one of my treatment visits, and the injection did help acutely as well. The way the symptoms diminished reminded me of an Imitrex (sumatriptan) injection, which I use as a rescue medication at home for more severe/advanced migraines. Also, I have learned that the CGRP drugs tend to build up and work better over time, which is the opposite of every other drug and lifestyle change I’ve ever attempted.
K: You said [in previous correspondence] that you “suspected the dose was too low to have a *huge* impact.” What did you mean by that?
As far as dosage in the Amgen study, there were two sort of “false hopes” that were brought up during the duration of the open label phase that didn’t come to fruition: one was that the open label phase might be extended to five years; the other was that my dosage might be doubled. That is when I first learned that my current dose was considered low. Neither of those possibilities actually occurred. The reason I didn’t get my dosage increased was because I was too close to the end of the study, but the nurse research coordinator and I definitely assumed that a higher dose would have higher effectiveness, particularly because of the length of time I have been dealing with my illness, and its severity.
K: Did you have improvement in symptoms other than pain?
E: For me, that is such a tricky question. Pain was the most noticeable improvement, and general mood. I feel I noticed my other migraine symptoms much more, but that could be because the decrease in painful episodes made them more obvious. There were many days I had very low pain, but very significant aura, nausea, vertigo, and allodynia. In fact, once I vomited before I even felt the pain in my head, which had never happened before. I did remain very fatigued all throughout the study.
K: Have you have any side effects?
E: I had none from AMG333. No side effects whatsoever… unless you consider decreased depression a side effect, which is something I considered. The only side effects from the drug in the second study were swollen bumps at the injection site, which disappeared in a few hours.
K: Can you put a percentage on the overall improvement from the drug in the first study?
E: From AMG334, I would estimate a 20% improvement. My pain was less severe and easier to treat; I was more active, and happier.
K: Did you complete any quality of life questionnaires as part of the study (like MIDAS or HIT-6)? If so, do you know what your scores were?
E: I googled MIDAS and HIT-6 and yes, questions very similar to those were asked at every visit. I don’t know what my scores were, and in fact I never have known what my scores have been any time I’ve taken them over the years and wasn’t aware I could ask! With both studies, quality of life was considered, rather than pain only. Also at every visit I took a survey regarding depression and suicidal thoughts.
K: Did you have any improvement before the open label portion of the Amgen study?
E: Honestly, it was hard to tell. I was still having migraines nearly every day. I would have thought my improvement was negligible, except for the way my activity increased. During the double-blind part of the study, I began volunteering for the curator at the nearby historical museum, helping build the musical recording and sheet music archives. I joined my daughter’s youth theatre group advisory board, and auditioned for and got a part in The Best Christmas Pageant Ever. I didn’t miss a single rehearsal or performance. Since 2013 I had been unable to work or do much of anything, so my sudden ability to participate (and even to have interest) in community organizations is very telling.
It could be argued that simply being involved in the study was increasing my level of hope and happiness and therefore affected my migraines and other areas of my life that way. Or maybe I actually did get AMG334 from the very beginning.
K: How long did the benefits of the medication last?
E: My last treatment with AMG334 was in February. I didn’t see a significant increase in pain between then and my first treatment in the new study in early July 2016. My friend said that almost all of her patients maintained some improvement after the treatments stopped. For me, this is huge. Not only is there such hope for migraine prevention in the future, but it also seems to work better over time and have a lasting impact on the brain function of those who use it. The benefits build up in our brains, rather than our brains / bodies becoming accustomed to the drug and developing an immunity or tolerance.
K: Do you believe these drugs will hold as much promise as the migraine community is hoping for?
E: We have every reason, as a community, to be very excited about these developing medications. There are other forms being studied as well, even an oral one, which may be a lower cost alternative. I think the CGRP developments are going to completely revitalize migraine care due to the medicines’ possible uses as both preventative and acute treatments, as well as the long term positive effects on the brain. Even though my improvement has been difficult to quantify and it may not sound like much, with what I said about still needing the ER and using the same amounts of medication, that could change with this second study. Even if it doesn’t, if I maintain the same happiness and level of activity, that is a quality of life improvement that is hard to argue with.
I really do believe that once doctors have access to the approved medicines, they will have the ability to give larger, more frequent doses to patients with nearly or completely intractable pain. Maybe with higher doses and more frequent administration, we can all get to the point where our quality of life is much better.
Elizabeth Roberts-Zibbel lives in Bowling Green, Ohio and is married with two daughters, ages 7 and 11. She blogs at Lady Migraine and is highly involved in her daughters’ activities, serving on the youth theatre advisory board and is a dedicated backstage crew member. Elizabeth also assists her partner John with his website business and occasionally serves craft beer at a friend’s nano brewery.