I just read the lithium study

[wright]

Hey guys

I was sent the lithium study by a fellow ALS forum member (Mark) and it certainly appears to be very well done. It was a double-blind study (with the exception of one physician who needed to know who was getting lithium to adjust levels if needed . . . but that physician did not evaluate any of the data). As the initial rumors had it, lithium significantly slowed the progression of the disease. There were a number of parameters used to asses progression: ALSFRS-R scale, Norris scale and forced vital capacity to measure lung function. There were 16 test subjects who took lithium (25% were bulbar . . . that is . . . 4 of the 16) and 22 controls who took a placebo (29% were bulbar . . . that is . . . 7 of the 22). All of the lithium-taking PALS survived and stayed relatively stable over a period of 15 months. There was definite decline in health in the control group, along with about 30% who did not survive (they didn't indicate if they were bulbar or limb-onset).
This clinical study was more or less rushed to be started because of the promising data they had gathered previously in an animal mouse model and in cell culture. They showed that lithium was able to actually cause an increase in a certain type of cell (Renshaw cells) in the spinal cord (these cells are not motor neurons) thought to be involved in the disease process of ALS. They also showed how lithium "stabilizes" certain structures of motor neurons that help them survive, showed that lithium causes the motor neurons to get rid of structures that cause damage, and that lithium promotes a number of other processes that keeps motor neurons from dying.
The only draw-back in the study is the small number of participants. Sometimes when a study is this small, it doesn't always give a true reading. However, from what I understand, they are going to have a much bigger trial, and I'm sure there will be many more studies to follow this one in clinics around the world and I'm sure those studies will be large ones.
Bottom line: it certainly looks promising to me. Again, the study was well done, so I think we should all be hopeful. As I've seen on here, there are a number of you already taking lithium, so keep us posted as to your progress . . . or should I say . . . slowing of progression. :mrgreen:

[ZenArcher]

This is all I have to say regarding the study size:

The study protocol was approved by the Neuromed IRCCS Ethical Committee, and all subjects provided written informed consent. Initial statistical analysis determined that at least 40 subjects were needed to determine, with a 95% confidence interval, a survival increase >6 months.
The present study was performed on 44 patients (20 male and 24 female).

[wright]

In the "study design and patients" the study indicates that they have 16 individuals for the experimental group and 28 individuals for the control group. However, further down in that same section, it says that there were 22 individuals for the control group. I'm not sure what to make of that. I'm amazed that the reviewers of the manuscript didn't catch that.

[jimercat]

Didn't some of the control group die, not only from ALS, but from heart attack, etc...?

[ZenArcher]

The study states that 29% of the control group died within the 15 month test meaning 8 people while all those on lithium survived. There have been reports elsewhere that two of the test group died prior to the two year mark one from a heart attack and one from ALS related causes due to advanced bulbar symptoms at trial onset but neither of these are within the scope of this paper.

[dona jean]

there are quite a few folks that are already taking lithium, of coarse they just started durning january, so no one really has any feed back yet. i go to my als clinic at univ. of va. next wednesday and i am going to discuss taking the lithium with the dr.s there.
dona

[northerngirl]

Have not seen the side effects from taking lithium, but on another forum some of thier doctors are saying what the heck, what do we got to lose. we know the drug, it has been around for a long time. And some doctors say no way it has not been approved. I have my fingers crossed and my prayers sent that this will open a little window.

[stevef]

This does look promising. What is it going to take the US based research sites to start an experiment. It sounded like on the MDA?ALS site they mite be looking into it. Something need to be done to get the ball rolling for a bigger study especiall int he US and Canada

[Al]

Don't know if I'm supposed to say yet but a large Canadian hospital is going to be doing a larger phase 2 trial. They just need to get the paper work done.
AL.

[stevef]

Al

That would be great. I wonder if they are keeping it low so not to get people's hopes up. Are you going to be taking part in it. If so keep us informed. I will be praying extra hard during this lent season for a cure or anything to improve and prolong life. May God bless everyone in this site and those who have ALS that are not in this site.

[CindyM]

All this sounds promising and very hopeful. Finally some good news!

[stevef]

my question is if they are going to do a study here in the US or Canada how do they chose which ones get Lithuim or just get riluzole. I mean how can a study chose to use it on some and not on others. Do you think they will now just test the effects on Lithuim and not use riluzole in the process. What i mean what are the ethics used to determine who might live longer and who might not.

[Al]

It is my understanding if you are taking Riluzole you will continue and if not then just the lithium will be used. Not everyone wants to take Riluzole. In a phase 2 trial everyone gets the Lithium.
AL.

[ZenArcher]

I walked out of clinic today with a prescription for lithium carbonate 150mg 2x/day and blood work every two weeks. I had sent the report to my neuro as soon as it posted along with what I'd like to do and why and here we are. I'll take the first dose tomorrow morning and do the first blood work next week.

[kelly]

We just came back from an ALS clinic appointment. I asked them about the lithium studies, and they said they did not hear about them yet. I am impressed that you were able to get your prescription from your Doctor. Nice that you have a supportive neurologist.

[ZenArcher]

I went in all researched up and ready to argue but didn't have to. I was ready to talk about HSP-70 and how lithium has the opposite effect on GABA as minocycline and how safe lithium was at these levels..etc,etc. Instead I got, its an old drug that we have a lot of experience with and its safe at these levels so here you go. I must admit it was quite refreshing but I was disappointed I didn't get to even debate a little :)

[TipaCow]

lol Jeff Good luck!

[pmbenb83]

Good luck Jeff. Please, let us know how you feel on the medication.

Take care,
Pam B in Va

[ilgal]

I started taking 150 mg. lithium twice a day on Jan. 21st. At 5 days my blood level was
.3 so increased dose to 3 times a day. Will have blood level checked again 2/11. So far no side effects.

[dona jean]

I am going to my als clinic next wednesday, and i am hoping got my scripts too!
Karen Felzer at cal tech kfelzer@gps.caltech.edu is conducting a study, and if you email her she will respond, and answer any questions you have. hope this helps.

[givenin]

My husband showed me the clip of the study on his computer last night, it is good to see his hopes go up but he is also progressing into Bulbar very quickly. My question is what are the side affects? I have heard nothing of what they could be and fear that if he should try another experimental drug his quality of life would even be worse than it is now.

[sharonca]

My doctor told me at the levels we are to take - 150 mg 2 times a day - that the side effects should be minimal. The most I have noticed after 6 days is a dry mouth at night and that could be because I heard someone else mention that. It is not a big deal. We are trying to get to .4 blood level. Someone taking it for bi-polar would be at 1.2 blood level. For me, the chance that this could slow or stop progression while I can still use my hands and speak would be - can't think of a word great enough. I have my first blood test to check levels today. Wish me luck!

Sharonca

[northerngirl]

Mom just got back from the ALS cllinic in Vancouver, They told her they Have quite a few PALS taking it and have been for a while, they have not been able to see any benefites so far. They did tell her thier hope is still in stem cell.

[stevef]

Well that is not good news northerngirl. I hope that is not the case and the people you are taking about have not been on it long enought to show any improvement. it is also my understanding it is not a cure but a way to prolong life and improve life. God lets hope it works

[dona jean]

fyi...there is another artile published by the als association yesterday. i am sorry i do not know how to send it to this web site, but is anyone wants it email me
dtownsend24@cox.net and i will send it to you.
jeff (zenarcher) are you also taking rilutek while taking the lithium. did
you dr say if it was a good idea or bad idea to take both at the same time?
thanks

[ZenArcher]

Dona, is this the MDA page you were talking about?

http://www.als-mda.org/research/news/080204Lithium_slows_ALS.html

Yes, I am still on Rilutek at 50mg 1x/day. My liver didn't like 2x/day so I've been at once a day since October or so. There are no issues taking both at the same time.

[dona jean]

thanks jeff. did you report out how much lithium you are taking?
i am going to my als clinic on wednesday and want to have all the amo!
dona

it is what it is: no pitty parties here

[vmd]

You guys may already be familiar with this study, but I will describe it anyway (From the Dana Foundation's Brain Work magazine). Jeff Rothstein, from Johns Hopkins, wrote about his research on the effects of lithium on astrocytes (glial cells responsible for providing nourishment to neurons). According to the report, ALS progression is partly determined by astrocyte dysfunction. The report goes on to say that one of the functions of astrocytes is to remove excess glutamate from the synapses, where it could have a toxic effect. I quote from the article: "Astrocytes are equipped with an array of so-called glutamate transporters to perform this cleanup. In ALS, there is an 'almost complete wipeout' of glutamate transporters and astrocytes, Rothstein said suggesting that these transporters are crucial in neuron death and disease."

Since lithium targets glutamate, the neural protection lithium offers may be related to balancing glutamate levels.

[Shawn]

hey Al, do you see Zinman?
I sent him a link, thru Myrna, describing the lithium study and I'm due for my visit on the 19th, i think.
do you think he'd be ok with it?
he didn't email me back.
i've talked to him before about it, 3 months ago in fact, and he seemed very interested!

[ZenArcher]

Dona, as I'm sure you know the amount of lithium you take is dependent on blood level. I'm starting at 150mg 2x/day. I'll get my levels checked next week then go from there.

vmd: A couple of things I've found interesting is that lithium also induces HSP-70. Arimoclomol is a co-inducer of HSP-70. Also lithium regulates GABA to normal levels which is exactly the opposite of minocycline which inhibits GABA. I can post links later if you want just don't have them now. Search PubMed they're there.

[vmd]

I've seen a few articles here and there. Is PubMed information free or does one have to subscribe?

[ZenArcher]

The abstracts are free most of the full articles have to be paid for. That is unless you have access to an online library from a college or something similar.

[Al]

Hi Shawn, welcome. I do see Zinman and he sent me an email. They are probably going to be doing the large phase 2 trial there. Paperwork has to be done first. They have to have parameters set up so that everybody starts on the same page so they can properly track it all. I would expect most of us will be asked if we want in it.
AL.

[Shawn]

ok, thanx. i wonder how long paperwork takes!
funny how impatient we can become!
:-D

[cheryilyn]

I asked my dr. about lithium awhile ago and she said no proof and too many side effects.

[ZenArcher]

Let me preface this by saying I can understand a doctors reluctance to prescribe lithium off label at the same time though I wonder how many of those same doctor have taken part in drug trials for ALS. Arimoclomol for instance had only been tested on mice so its effects on humans were unknown but doctors gave it to patients. Minocycline had been used in humans but not for ALS but it was given and increased the progression of symptoms by 29%. Lithium has been used for years and the first 44 were the test subjects. It has been tested safe in humans and shown to be safe for ALS at least over a 15 month period. I will admit the test needs verified but it shows with 95% certainty that lithium increases lifespan > 6 months over Rilutek alone.

Again, I'm not trying to argue for or against lithium. I've made my own decision. I'm just thinking out loud here :)

[dona jean]

i talked to the nurse practicioner at my neurologist office yesterday...she said she hadn't seen any of the studies and would not prescribe the lithium, but she promised me she would research and get back to me. she was totally sceptical about getting involved because of the minocycline deal where it accelerated the als instead of slowing
it down, and she says the lithium has to have a good track record before they would prescribe, blah blah blah blah blah!
i have sent a bunch of info to my gp who is very thorough and i know she will get back to me real soon, she was amazed as i am her first female patient with als, which i think makes her more interested.

i will know more when i go the u va for my clinical appt on wednesday, but i am thinking
it is time to find new neurologist, i hate dealing with doc-want-to-bes (nurse practicioners) anyway, and after i was diagnosed my neurologist turned me over to her
as if he was done with me.

sorry for rambling! thanks to anyone who read this, guess i needed to blow off steam!

[ZenArcher]

Dona forgive the upcoming fervor but WTF!!! I would politely tell your neurologist and his nurse practitioner to copy all your records for you and have a nice life. Talk with the ALS Association chapter in your area: http://www.alsinfo.org/contactus.html and see if they can recommend a neuro in your area. There is no way in hell I would let them get away with sending me to a nurse practitioner. Sorry that just struck a nerve.

[dona jean]

thanks jeff!
i feel that way, i already told my husband that i am gonna find a new neuro
he agreed, he didn't like them either!

[sharonca]

Dona - What I did is copy all the research from the site and took to my doctor's appt with me. He then had the research right there. I was more fortunate than you in that he was already willing to be receptive to what I had in mind. But I was prepared to answer any question with paperwork that he could easily verify. This was my GP. My neuro called me and when I explained my plan he asked for the web site and wished me luck. Be prepared and go for it!

Sharonca

[northerngirl]

My feeling are any neuro that deals with PALS who has not heard of the Litho study by now, is not very diligent with what is going on out there. More importantly if you ask and they don't take an genuine interest in what you are saying, and are not interested if looking in to it (supportively), then maybe it time he/she retired. :-D. It's your life not theirs that you questioning.

[dona jean]

thanks you guys for you input.
hopefully when i get back from my clinic visit on wednesday, i too will be on the program.
thank you all for your advice

[northerngirl]

Previously I said Mom had go to the ALS clinic last week in Vancouver, And apparently she meant they told her may of there PALS were using Rilutek with no notable improvements. I asked them about Lithium And they said they were looking in to it and probable would give her a prescription. I am waiting for a call. Mom was over whelmed at the clinic and missed that one.

[Jamiet]

You scared me there northerngirl...

[Al]

http://www.youtube.com/watch?v=210IHwqkdp8

Jamiet sent this to me. When I was a boy my dad told me don't believe everything you read and only half of what you see. That was before Photo Shop and being able to alter pictures. I have no idea if this is legit but it is great if it is.
AL.

[Jamiet]

Al, when i was young, i was taught, it was none of what you hear and 1/2 of what you see ...lol....same ending.

I know Jeff got this too. It seems to be pretty legit.....

This all seems to good to be true yall. Cautiously optimistic as Jeff said.

[adams4]

i Walked Out Of Clinic Today With A Prescription For Lithium Carbonate 150mg 2x/day And Blood Work Every Two Weeks. I Had Sent The Report To My Neuro As Soon As It Posted Along With What I'd Like To Do And Why And Here We Are. I'll Take The First Dose Tomorrow Morning And Do The First Blood Work Next Week.

I Am Was Wondering How You Are Doing Since You Started Lithium. Have You Had Many Side Effects? I Am Going To Be In A Study This Oct. For Lithium And Trying To Get Any Info I Can.

[ZenArcher]

I was on lithium for almost 3 months and had a level higher than 0.4 mmol/Eq for over 2 of those months. In that time I developed speech issues and weakness in my legs. I do not know if this was simply disease progression or due to the lithium but I wasn't willing to take the chance so I quit lithium.

[cynds]

I was diagnosed with ALS last month. My doc would like me to start the riluzole/lithium regimen as soon as my blood work is back. I've read the Italian study (you can find it here if you would like to read it - http://www.pnas.org/content/105/6/2052.full) and have a few problems with it. I think the biggest problem I have is that it really does seem like a big risk (known and unknown side effects) for a small return (a month or two longer life). Don't misunderstand, I want to be around as long as possible, but I'm not sure these drugs offer me the best quality of life.

I would welcome others input on this.

Thanks.

Cindy

[patricia1]

I think by now we would have heard good things about Lithuim from people n the forum.
Lithium so far have not convinced me it works


Pat1

[sharonca]

I'm staying on Lithium. No side effects. I've progressed in my legs and slowed progression in my hands and mouth. No reason not to stay on for the year of the study at PLM.

Sharonca

[tmasters]

I can't tell if there's been any benefit but I'm staying on Lithium for now. No reason not to for me since there are no major side effects and it's safe and inexpensive.

At the 3 month mark, Karen Felzer's analysis of the grass-roots Lithium study are not encouraging. But it's still early. This is a marathon.

-Tom

[Al]

I and a few others from my clinic quit before 3 months due to accelerrated symptoms.

AL.

[gimpydad'slady]

My hubby also quit taking Lithium due to accelerated symptoms. He took them a month, and that was it, things were crazy for a couple of weeks afterwards, but things have gone back to somewhat "normal" in comparison to how things had become while taken the lithium.

[Tall John]

Tried for 3 months, levels over .4 for at least 2 months. Did not slow and may have slightly sped up progression.

I'm as hopeful as the next for some breakthrough, but Li won't be it; too many above feel like me. Things feel pretty hopeless.....

[Charlotte Feldman]

My husband was diagnosed with ALS in December, 2007. It began as a slight difficulty in speaking and progressed to severe bulbar symptoms and weakening of the right side of the body. The well-known ALS Center at a famous medical center in our area had not heard about the Lithium study. Our older son sent us a link to the Italian study. He got it from a physician friend of his. While 'our' ALS Center had not heard about it, our own primary care physician visited with us and brought a colleague who is a neurologist and he HAD heard about it. They thought we should try it.

My husband has been on the Lithium as well as Rylatek since July of this year and we are hopeful. We did not want to wait for 'our' ALS Center to start 'their own clinical trial since those things take from eighteen months to two years and we may not have that much time.

Once 'our' ALS Center heard that we were "on" Lithium, they asked that we keep them posted and of course we have my husband's blood tests and EKGs as required, since Lithium has, like all drugs, side effects.

I pray for all of us ALS families and share your hopes, fears and dreams for a cure some day. After all, they once called Polio, Malaria, Smallpox, Tubercuosis, Diabetes, and so many other diseases untreatable and terminal.

The only good thing I can say about this illness is it give you time to find out who you are, how much you can take, and especially, who your true friends are and who are the fake friends who do not or cannot offer help.

[Jennifer51]

I can't tell if there's been any benefit but I'm staying on Lithium for now. No reason not to for me since there are no major side effects and it's safe and inexpensive.

At the 3 month mark, Karen Felzer's analysis of the grass-roots Lithium study are not encouraging. But it's still early. This is a marathon.

-Tom

I saw my italian nuero in london yesterday..he was in Rome in August with the doctors in the italian trials....it seems they are not TOO convinced by it but they have yet to collate all the final information and write up the findings which should be published fairly soon. At present lithium in not allowed in the uk for als, but they will look at the final italian results and see if they want to do a similar trial. The mnd association are going to run some trials in the UK soon but we dont know what the trial is about yet.
jennifer51

[John1]

I saw my italian nuero in london yesterday..he was in Rome in August with the doctors in the italian trials....it seems they are not TOO convinced by it but they have yet to collate all the final information and write up the findings which should be published fairly soon.
Hi Jennifer,

I'm not clear from your post as to what study your neurologist is referring to when he says they will be writing up the findings soon. Is it the Italian study (already published) or the patient-run one, mostly in the US and Canada?

John

[givenin]

I would be interested to know how far along those are who are taking Lithium that are not experinecing accelerated symtoms and those who are? I have been off for awhile and am interested as there are others in town here with ALS that are asking. As for my husband his symptoms speeded up very quickly and I believe taking it put him over the brink after a month and a half.

Cheryl

[ilgal]

Ill just tell you my progression. I started taking lithium in Jan. and was over .4 within a few weeks so have about 7 months at the target level. MY Functional Rating Score has declined from 37 to 26 in that time with a big drop in the last month and a half. My speech is terrible and I'm using a speech generating device part of the time. My ability to walk is heading south and writing is very poor. Surprisingly, and thankfully, I'm not having any breathing problems. In July my FVC was upper 70s and I don't think it has changed. So, do I think the lithium helps? Nope, and Ill probably quit taking it when the current bottle runs out.

What about others? Is anyone being helped? And when will someone really find a cure? I'm still praying.

[John1]

I too have been taking Li carbonate since January and reached the >0.4 level in the spring. I can see no change in my progression rate and my symptoms have continued to worsen, particularly in my hands and legs although not enough to change my ALSFRS-R score which has remained at 32 since January. My progression has always been slower than average. I am waiting for the 6 month Li report which I expect to be out soon. If it shows no value in the Li, as the 3 month report did, I will likely drop it.

[Jennifer51]

Hi Jennifer,

I'm not clear from your post as to what study your neurologist is referring to when he says they will be writing up the findings soon. Is it the Italian study (already published) or the patient-run one, mostly in the US and Canada?

John

I dont know..he just said he was in rome (in August) with the doctors and patients on a lithium trial...could it be a follow on .? My neuro is italian, which is why I went to him..he has a wonderful reputation and I thought he would be more interested in the italian trials, so if anything good came from it, then I thought I could be closer to getting help. The neuro who DX me is such a bighead and would not consider anything I put to him...he has a dreadful reputation with most of his patients and healthcare workers. so at the moment,sorry I cannot clarify anything. Likewise I know that the mnd association are trying to run a trial in the uk...we are currently fundraising for it...but I have no idea what that one is about yet

[John1]

Jennifer, perhaps it is a follow-up to the initial results that came out late last year. It would be interesting to know how the original group of Li patients is doing now. Please keep us posted if you hear anything.