Forego riluzole for a chance to enter Dexpramipexole study now?

[StillSteve]

I have an appointment on Monday to be screened for the Dexpramipexole trial. I've been told--based on the medical records I have submitted and a phone conversation--that I appear to be a good candidate.

The nurse who is coordinating the study at my location seems concerned that I've chosen to not start on riluzole so as not to delay my possible entry into this trial. She mentioned that if I started riluzole now, there will almost certainly be a spot available for me in 60 days. I told her that I wasn't all that enthusiastic about riluzole, and that my neuro was fairly negative about it. After I got my definitive ALS diagnosis from Dr K in February, I had to bring riluzole up to him (not the other way around), and he told me that it was "up to me" and that approximately a third of patients choose to use it. When I asked him to tell me what *he* thought about it, he said that it seems to provide only a marginal benefit, and said again that it was "up to me." Not really very helpful, but I definitely got a negative vibe from him about it. My predisposition based on what I'd read up to that point was that it probably wasn't worth taking, and so I didn't pursue it further.

Now I'm being told by this nurse that Dr T (the doctor who will be heading the Dexpramipexole study in Minneapolis) will want to talk to me Monday about my choice. According to the nurse, she (Dr T) is more of a proponent of riluzole than Dr K is, and believes that ultimately what will be most helpful for PALS is a combination of drugs, "a cocktail," to fight this disease.

So I think this doctor will encourage me to start on riluzole, which will delay my entry into this trial (by 60 days plus however long it takes me to get a prescription for and start riluzole). I've read a lot on this forum and elsewhere about riluzole, and opinions vary to say the least.

I'm a slow progressor so far. Twenty months or so since first symptom, my difficulties (aside from generalized fatigue) are still largely limited to my left arm and hand, though I know my right hand is weakening. EMGs have shown evidence of involvement in my left leg, right arm/hand, and lower back. No bulbar symptoms yet that I can tell. I'm 50 and otherwise in good health. I've gained 10 pounds over the last year, and my last measured FVC was 82% (basically unchanged from my previous measurement almost 9 months earlier).

Am I doing the right thing in foregoing the riluzole for the 50% chance that I'll get the real thing in this trial? Phase II results were encouraging, but it may not pan out even if I do get the right thing. On the other hand, if results are good, I will be eligible to receive the real drug at the conclusion of the trial even if it turns out I was on the placebo. There's at least some chance that in 60 days there won't be a opening for me in the trial, and an even smaller chance that because of an accelerated decline, I wouldn't be medically eligible. Plus, I will be getting quite close to the two-years-since-first-objective-symptom eligibilty cutoff.

What to do? Any advice from fellow travelers?

- S

 

[Alyoop]

Steve. It is a personal choice. I work in clinical trials and I know historically they tend to recruit below what is expected. The companies tend to be a bit optimistic, although I would think ALS subjects would be highly motivated. Why don't you ask your nurse how quickly it appears to be recruiting.

In our country riluzole is not available as the cost versus the benefit, just doesn't make it worth using. We have a system like Canada. The benefit of 2 - 3 months increase in life expectancy for some people makes it just not worth it.

The fact that you are presently stable and will have the opportunity to take part in the open label extension phase of the study, is a pretty important factor in your decision.

Unfortunately it seems like you are in a difficult corner. See the Investigator, hear what he thinks about riluzole, let him sell it to you, check about expected recruitment times and the present rate of recruitment, then maybe the answer will come to you.

Sorry I am of no help.

Aly

 

[notme]

It seems so unfair to you PALS that most of the trials have that '2 years since onxset" rule==when for so many it takes that long to even get a diagnosis!

Whatever you decide--at least if you do the trial--you'd be helping with what could ultimately prove to be a beneficial treatment of this horrible disease.

I just don't see the benefit of a medicine that only extends life 2-3 months--unless those 2-3 months are months of QUALITY. If they diagnose me--I'd be very close to the 2 year mark--if they count the UMN stuff that's been going on quite a while with the relatively new LMN things that finally made docs take notice of my issues.

 

[lgelb]

If you want to be in the trial, I would not let riluzole stand in your way. They should be scrupulous re 2y post-diagnosed and if you have to d/c for any reason, that could further delay entry. From the protocol summary, "if a patient has never taken Riluzole [sic: the generic should not be capitalized], he or she is eligible; if a patient is currently taking Riluzole, he or she must have been on a stable dose for at least 60 days; if a patient has discontinued Riluzole, he or she must have stopped taking it for at least 30 days." These are likely minima for any ALS trial, BTW. So 'twere [initiating the drug] done, 'twere best done quickly.

Riluzole is your choice in the US and ideally a separate one. While only you can decide treatment for yourself, I agree that polytherapy will be needed, but not necessarily that riluzole will be a part of the optimal regimen, given that emerging approaches as simple as weight maintenance have shown potentially comparable or greater efficacy to date, esp. in limb onset dz.

Full disclosures: my PALS is not on riluzole and I have worked for its manufacturer.

 

[StillSteve]

Thank you for your comments. I agree with you, notme, that the two-years-from-onset rule is unfair. It's interesting, lgelb, that your PAL is not on Rilutek given your association. I appreciate your comments, Alyoop, and disagree that you are of "no help." I actually did exactly what you suggested I do.

Here's what has happened since I posted on Thursday:

Dr. T called me yesterday to talk to me about my choice to not be on riluzole. Since she's never met me (there are two ALSA-certified clinics in town and I go to the other), she wanted to be sure I was comfortable with my choice, and understood that once I started on the study would not be able to start riluzole until its completion.

She told me that she is more of a proponent of riluzole than some doctors and explained why. Since the initial study, she said, every time its effectiveness has been looked at, it has been shown to be helpful. Because it is the only drug approved for ALS, it is unethical to not allow patients to be on it during trials. So at the end of each trial (she mentioned Celebrex as an example), it is possible to look back retrospectively at groups of patients who were on riluzole versus those not on it. In every case, she said, patients of riluzole do at at least a little better than those not (as measured by FRS score).

She believes that any successful treatment of ALS will be a multi-faceted one, and that riluzole's glutamate-blocking function may be a part of it.

When I brought up my doctor's seeming unenthusiasm for the drug and his statement that "about 30% of PALS choose to use it" she said that studies show that participation is highly correlated with the physician's feelings about the drug. Further, she thought his 30% figure was low and that the primary reason PALs choose not to use it is price. When I brought up side effects, she talked about a small percentage of users who notice increased fatigue and said that if this is the case with me I would definitely notice it within the first week (it would not be "a little more fatigue" but very noticeable) and that I could choose to go off the drug.

Then we talked about the big question for me, what are the chances that starting riluzole now will cost me a chance to get into the dexpramipexole trial?

She believes that it's almost certain that they (the Minneapolis location) will have spots open. They've filled only two spots so far, and are getting through applicants at the rate of about two per week (I didn't ask why so slow, but I was told that the appointment to confirm my eligibility would take 2.5 hours). They will enroll 20-30 patients (and the Mayo Clinic 90 minutes from here will enroll a like number). I will still meet the two-year-from-onset criterium (barely), and at my current FVC number and apparent rate of decline, I should be OK.

I was told to think about it and talk to my wife about it before my Monday appointment, and that if I decided to start riluzole, to do it as soon as possible. They would schedule my screening appointment for 32 days after I take the first dose. Then if I qualified, I would be guaranteed a spot, and 28 days later, I would start on dexpramipexole. She told me what I would need to do to get the prescription over the weekend (call U, ask for on-call neuro resident and ask for 30-day script).

An hour after I talked to her, I called the University. I took my first dose (50mg) of Rilutek last night.

I'll call on Monday morning to cancel my screening appointment and to schedule a new one (on Tuesday July 5, I hope). If all goes well, I hope to start the trial on August 2nd. We'll see.

By the way, Dr T called me at 4:50 PM on a Friday evening and we spoke for 40 minutes on the phone. My wife and I both agree that she spent more time talking with me (and listening!) than my current doctor has in five visits! I was very impressed with her. She freely admitted her bias in favor of riluzole and that other doctors felt differently, but then explained her reasoning in detail (and did a far better job of it than my brief account above shows).