Hyperalertness - Research Study

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ViewsAskew
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Hyperalertness - Research Study

Post by ViewsAskew »

We've talked before about how you can get very little sleep and function remarkably well compared to people without WED who get little sleep. Over time it catches up some, but after 30 years of this, I'm still amazed that I can get up after a couple hours, have WED, and be pretty darn awake.

Johns Hopkins is studying this phenomenon. Here is a link to the study info: http://clinicaltrials.gov/ct2/show/NCT01675323

And here is the text:
Glutamate, Hyperarousal and Restless Legs Syndrome
This study is currently recruiting participants.
Verified August 2012 by Johns Hopkins University

First Received on August 27, 2012. Last Updated on August 28, 2012 History of Changes
Sponsor: Johns Hopkins University
Collaborator: National Institutes of Health (NIH)
Information provided by (Responsible Party): Richard Allen, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01675323
Purpose

Restless Legs Syndrome (RLS) research has focused on the sensory features and failed to address an important aspect of RLS; i.e. a 'hyperarousal' or profound chronic sleep loss without significant excessive daytime sleepiness. This hyperarousal produces RLS symptoms by overwhelming the normal inhibitory processes needed to decrease sensory and motor cortical activity for resting and sleep. Thus the hyperarousal produces both the RLS need to move when trying to rest and the inability to maintain sleep. The biological consequences of this hyperarousal process on sleep (increased wake time) and cortical excitability (as demonstrated by transcranial magnetic stimulation (TMS)) are postulated to reflect increased degree of excitatory glutamatergic activity, and therefore affected brain regions will show relatively increased glutamate (Glu) and glutamine (Gln) on MR spectroscopy (MRS). Changes in inhibitory activity and GABA may also occur, but less significantly than the increase in Glu/Gln. Our pilot MRS data discovered a new abnormality in RLS: increased Thalamic Glx (Glu + Gln) that correlated well with sleep measures of hyperarousal. Glx levels are not specific for the neurotransmitter role of Glu.

In this project RLS and matching controls subjects will be studied using polysomnograms (PSG) and TMS and 7T MRI for MRS that provides accurate measurement of Gln levels, which reflect mostly neurotransmitter Glu activity. The first aim is to confirm that Gln is increased in the thalamus and to determine if this also occurs in the motor and sensory cortices. The relation between Glu, Gln and GABA will also be evaluated. Second, assessments will be made of the degree of relation between Gln increase and the hyperarousal effects on sleep and cortical excitability (TMS). This would demonstrate that abnormally increased Glu activity is primary to RLS hyperarousal and radically changes the emphasis in RLS to be less on dopamine and more on Glu-hyperarousal as a major feature of RLS.This is an entirely new direction for RLS research and treatment development. The new concept of hyperarousal adds a missing dimension to understanding RLS, namely the discovery of the Glu abnormality and its central relation to the other hyperarousal features.

Condition
Restless Legs Syndrome

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Glutamate, Hyperarousal and Restless Legs Syndrome
Ann - Take what you need, leave the rest

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Chipmunk
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Re: Hyperalertness - Research Study

Post by Chipmunk »

That is very interesting, although I would say that I likely have low levels of glutamate, which is why I need ADHD meds and why the amino acids help me sleep better.

I imagine there is a happy medium and, like so many other things, too much or too little causes problems. I am tired a lot too, but can't get to sleep at night. Have always been this way. I assumed it was because of the rls keeping me awake but now I wonder if it is a glutamate deficiency. Hmmm...
Tracy

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badnights
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Re: Hyperalertness - Research Study

Post by badnights »

I enquired about the requirements for participation in this study. You have to go off meds prior to the study, and stay off for 2-3 weeks, including one (paid for) trip to Baltimore with a 2-night stay at the hospital.

For me, this would mean probably 5-6 weeks of uselessness +/- torture. I would have to go on something else temporarily, while I weaned off the opioids, and I'm on opioids for a reason ... I would probably try pramipexole which I haven't augmented on, it merely made me unbearably drowsy, and maybe Horizant to avoid the high dose of pramipexole I would need otherwise. I'm a little leery of Horizant because it's a pro-drug of gabapentin which made me suicidal; I would have to find out if the side-effect profile is likely to be different.

Then once the opioid withdrawal was over, I could go off the temporary meds, and see what life is like for 2-3 weeks. I think I would survive because I would know there was an end, and I would be doing it for a very good cause. I am just not sure how I could possibly get to Baltimore from Yellowknife, NWT, with no meds. That's the biggest glitch at this point, even bigger than getting 5-6 weeks off work. The only solution I can see, and can't afford and it would be unpleasant, is to stay in Baltimore the whole 2-3 weeks of the study.

The study is going on for 3 years, so she's going to touch base with me again next fall. Meanwhile I'm going to talk to my GP about this, see if she'll support my doing it. I think it's hugely important, it's a very different direction of research than other studies, it's addressing a (to my mind) absolutely critical aspect of WED/RLS that is currently unexplained (the hyperalertness) so any explanations they come up with might lead to a real RLS medication , not these drugs made for other diseases and pressed into service for RLS/WED. Even Horizant, touted as the first drug developed for RLS, is just gabapentin dressed up.

If you want to see a real RLS medication, I suspect this is the type of study to watch. Or join.
Beth - Wishing you a restful sleep tonight
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Polar Bear
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Re: Hyperalertness - Research Study

Post by Polar Bear »

To consider what taking part in this study would cost you in terms of discomfort and symptoms and all the horrors that coming off a medication would inflict.
And then to be completely without medication for a few weeks ... ... to be considering such commitment is to be applauded.
Betty
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cornelia

Re: Hyperalertness - Research Study

Post by cornelia »

It certainly is to be applauded. I tried to come off meds (mainly Oxy with a bit of other meds) because my neuro suggested it. I only lasted 48 hours which had a severe impact on my life for 5 weeks after. I am almost certain that I have the stamina to withdraw from meds, but not with an illness as RLS. The not being able to sleep and ongoing RLS I couldn't cope with.

I think too that this can be an important study. I hope they will find enough people willing to partake.

Beth, did you ask if they take patients with severe RLS? I can see that with ongoing symptoms some tests just cannot be done?

Corrie

debbluebird
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Re: Hyperalertness - Research Study

Post by debbluebird »

Wow, that is very interesting. I would love to be in a study, to see what the results would be. I think I could handle going through the nightmare, but I don't think my husband could handle it. DEB

ViewsAskew
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Re: Hyperalertness - Research Study

Post by ViewsAskew »

A couple years ago when I stopped methadone and we were looking for an alternative would have been a perfect time! I was already miserable.

And, I just can't make myself want to be THAT miserable again! I wish I did...it's important, after all. But, I just can't want to do it.
Ann - Take what you need, leave the rest

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majoraward
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Re: Hyperalertness - Research Study

Post by majoraward »

badnights wrote:I enquired about the requirements for participation in this study. You have to go off meds prior to the study, and stay off for 2-3 weeks, including one (paid for) trip to Baltimore with a 2-night stay at the hospital.


It is unrealistic, in my view, to ask for this at the beginning of the study. It would be similar to asking a heroin addict to stay off the drug for 3 weeks so they could test them. If the addict could do that then they probably aren’t heroin addicts.

In WED/RLS case it is even more complicated because each individual is not only on different doses but on different medications. If they are going to do a study they should start it at a comfortable stage. For example, monitor participants at their homes, have a plan to bring each individual down from their medications to do the testing as fast as possible and to then have a plan to get them back on their medications. It doesn’t seem reasonable that a person with severe RLS would be able to travel far without any medications and maybe even dangerous, but then it looks like they are probably looking for local participants, limiting the study.

I have seen similar requests and I wonder about the kind of participants that they actually end up getting, probably participants more like I was 15 years ago when RLS would bother me a couple of hours at night a few nights a week. I could certainly have done the study then, at least locally, since I was not on any medications. It could be, I suppose, that even 15 years ago testing me may have given them the same data as today. The assumption that someone with severe WED/RLS may test differently than a person with moderate or less severe WED/RLS may be incorrect. I know it probably has more to do with the lack of funds for the study, but you get what you pay for as the saying goes.

badnights
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Re: Hyperalertness - Research Study

Post by badnights »

Well I haven't done anything yet except think about it and ask questions, so no applauding...

I wanted to ask, but haven't, and won't until I talk to my doctor, about whether they will still want me if I know beforehand I am not going to sleep (because I am not going to sleep, it would be a miracle). Since they're doing MRIs and blood and urine work, they might get good data despite the lack of sleep. But I have to check with them. I also want a more detailed description of the study.

As for the parameters of the study making it practically impossible to accept people with severe RLS, that is indeed a function of funding, and a reflection of the real-life restrictions on what's possible vs impossible. They have to take people off their meds otherwise they won't be able to tell what's an effect of the meds vs of the disease. I, too, wonder if they would get different data if more people with severe RLS were studied; but I can't imagine how that could happen, outside of a richly funded, medically supervised setting in which we would still suffer insanely. I would! gladly! if it would awaken the world to what this disease is like! I wish I was a promoter, someone should document the withdrawal, to prove that all narcotics are out of my system, then document the RLS, to show the world that THIS is what the disease is like!!! THIS is how we suffer! It is NOT trivial!

I will email her back and ask her how it would affect their study if I didn't sleep at all. (maybe she thinks it's not possible :roll: )
Beth - Wishing you a restful sleep tonight
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majoraward
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Re: Hyperalertness - Research Study

Post by majoraward »

That last sleep study I had a few weeks ago is a good example. They allowed me to take my Oxycodone, Lyrica, and Mirapex and I spent 3 hours trying to get to sleep when they finally came in and gave me Ambien too before it would happen. Then after the study they took me off Oxycodone and began Methadone again with Lyrica, Mirapex, and Ambien. If I were given no drugs now I would be up for at least a week before I would begin to fall asleep on my feet.

I haven't had any problems sleeping during this surgery thing (the only nice thing about the surgery) because they had been giving me Oxycodone, Methadone, Mirapex, Lyrica, Ambien and while at hospital a couple of different kinds of narcotics (can't remember the names but they were given through my IV drip for pain, and they switched them out), not to mention what the anesthesiologist gave me during surgery that made it so my brain woke up several days before my intestines (according to one doctor) - lol. Severe RLS/WED requires lots of medications for sleep.

badnights
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Re: Hyperalertness - Research Study

Post by badnights »

indeed :)

Well, I got more info. There are 4 SITs (Suggested Immobilization Tests) each 1 hour long, in 1 day, which would be torture but I could do it, because you don't have to be still, you just have to try to be still. It's also OK if I don't sleep at all during the two sleep tests. But what might be impossible is that I would have to endure a 1-hour MRI without moving my head at all, and preferably my legs only slightly, so as not to blur the images. Not sure how that would go over on Day 13 of no meds. :?
Beth - Wishing you a restful sleep tonight
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Polar Bear
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Re: Hyperalertness - Research Study

Post by Polar Bear »

On Day 13 of no medication it would be a nightmare to have to be still.
And presumeably because of the information required a one-off dose of something would not be an option.
Oh.. My.... that would be hard.
Betty
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majoraward
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Re: Hyperalertness - Research Study

Post by majoraward »

Polar Bear wrote:On Day 13 of no medication it would be a nightmare to have to be still.
And presumeably because of the information required a one-off dose of something would not be an option.
Oh.. My.... that would be hard.


Wow, that would be a problem. By then I would be constantly pacing, they would have to forcefully strap me down for any testing. I would hope the testers would all have some good earplugs :lol: It would look like a bad horror flick...

Even so, I might go through it if it were to help someday, although public transportation would be out of the question by then, they would lock me up before I arrived for the study.

badnights
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Re: Hyperalertness - Research Study

Post by badnights »

That's wha'ts worrying me most about it, how to get to Baltimore --- do I go before I get off meds, and suffer that whole nightmare in a hotel room I can' afford?
Beth - Wishing you a restful sleep tonight
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I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.

majoraward
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Re: Hyperalertness - Research Study

Post by majoraward »

badnights wrote:That's wha'ts worrying me most about it, how to get to Baltimore --- do I go before I get off meds, and suffer that whole nightmare in a hotel room I can' afford?


I think you have just answered your own questions, it is just not practical. Are there any studies going on up your way? I see that you live in the Northwest Territories, Canada; You must live around two thousand miles north of me at least I would think, I live in Seattle area. Do you live far enough north that it effects how much light you get there like up in the northern part of Alaska when the sun never rises or sets totally? I would think that would make RLS symptoms worse.

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