691 replies to this topic

[MarcB]

Nothing is completely without risk.

But our situation isn't "Nilotinib-or-nothing" -- forever.

Its "Nilotinib-or-something better" -- coming soon.

In a couple of years, we should have a better choice, or even several better choices from promising drugs already being tested now.

Here is my understanding of our situation:

"Gunk" accumulates imperceptibly for 20 years or more before symptoms appear.

We cannot clear 20 years in 6 months and so we do not want to risk our lives trying.

What we DO want to do is slow additional build up or even slightly reverse it to stay on this side of the tipping point and avoid the point at which the process greatly accelerates.

If we can do this for just two years, we will be candidates for the new medications. All we are waiting for is evidence that they are better than Nilotinib.

So, we are not putting all our hopes on Nilotinib to be "the answer". We need not risk desperately or hope irrationally.

All we ask is that a tiny bit of Nilotinib keeps us off the tipping point.

Even if it only works well enough to keep us just where we are for a couple of years until we switch to the better meds--- then we now have a future to protect -- just like anybody else.

At the very least, by then, our lonely, scary DIY trial will be over and our doctors will be willing to supervise, follow, and test our progress with Nilotinib !

 

Library,

 

When you speak of effective drugs being a couple years away, is that because you know  of specific drugs (perhaps PXR002 or MSDC-0160)  that could be fast tracked or are you speaking generically?

 

Thank you.

 

MarcB

 

[45rpm]

After reviewing all of the warnings about Nilotinib, here's the conclusions I have come up with.

 

According to one online source, 0.6 percent of cancer patients taking the drug died from heart problems. If the percentage is wrong, please correct me. If the percentage is correct, then that's less than one in 100.

 

Let's not forget that these people were ill with a serious disease, might have had a pre-existing heart condition, and were presumably taking the full 800mg per day dose.

 

On the other hand, a smaller dose seems less likely to cause heart problems. Is the drug without risks? Of course not.

 

Reading some of the first-hand reports on this website, it's obvious that some people can't tolerate larger doses of the drug. Unfortunately, according to one of the studies, Parkinson's patients who received larger doses of the drug reported the most improvement.

 

For the record, I recently took my mother off Nilotinib for a period of about two weeks because she was prescribed a prescription drug for an unrelated medical condition. It's very apparent that during this period, her Parkinson's worsened without the Nilotinib. She's back on Nilotinib as of yesterday and the first thing I noticed is that she now looks healthier.

 

 

[45rpm]

Here's a new supplement that might help those with early P.D.
 

https://www.scienced...70116160550.htm

 

I found only one source for the product and it's not too expensive.

 

http://cantron.com/h...cals/squal.html

 

 

[maxwatt]

Baicalin is promising in mouse models of Parkinson's https://www.ncbi.nlm...pubmed/18173149

 

https://www.ncbi.nlm...les/PMC4281409/

https://www.scienced...40827101441.htm

 

Now. back to nilotinib

[Library]

Some time in the last six months, I watched a UK presentation on Parkinson’s which I can’t find now, but I remember thinking “this is a sane review”. It summarised the known (2015) medically understood as influencers of Parkinson’s. The whole list was only 5 things.

• Smoking
• Coffee
• L-DOPA drugs
• Isradapine (Dynacirc.. a calcium channel blocker for blood pressure)
• And something else which I can’t remember.

I see that two drugs that I regularly consume are

• (unfiltered) Coffee is on the list of weak CYP3A4 inhibitors
• Dynacirc – on the list of CYP 3A4 Substrates

Additionally, I have occasionally taken courses of Erythromycin for chest infections (and less occasionally, Prednisone). Both are on the list of CYP 3A4 Substrates.

My Parkinson’s diagnosis was made in 2005. For the first 9 years, I used solely Aryuvedic remedies. These kept the disease largely in check for those 9 years. A year ago, I approached a neurologist about Nilotinib, and on their recommendation, started taking Western L-DOPA medication. I did this on the assumption (or more accurately, hope) that this would be a stop-gap. I started Nilotinib in Septmber 2015.
(See http://www.longecity...ndpost&p=791675)
I must mention that the Neurologist was dead against my using Nilotinib, but because I was determined, agreement was made to do the UKPDRS measurements.
(See http://www.longecity...ndpost&p=795067)
As I said then, I restarted at 50mg. Nilotinb per day. But I found that even at this level, adverse effects accumulated over time.
I am extremely grateful for your advice, Library. Thank you.
So I think that my next steps will be:

• To get another ECG. (I’ve had 2 already, early on)
• To approach my GP about an alternative to Dynacirc (and also an alternative to Erethromycin).
• To give up on coffee.
• To stop taking the Aryuvedic meds.
• Give myself a fortnight for the CYP3A4 situation to stabilise.
• Continue with the L-DOPA meds (I’m not getting any side effects yet)
• Getanother UKPDRS assessment made.
• Then start back on Nilotinib 50mg for 2 days and then nothing for 2 days.

Any comment welcome.
My sincere gratitude to all contributors.
David

[Library]

If accumulation is a problem, processing has been too slow--so you would need more time for your (inadequate!) CYP enzymes to catch up. I'd give at least a couple weeks and a month would be better.

The on/off dosing schedule is not a good idea because it confuses the EKG results --- since you don't know what blood level you are getting when, it can't tell you if you are ok or not.

*****************************************************************
WHAT YOU REALLY NEED

N is a long-term therapy so what you really need is to find what dose you can stick with and achieve a steady-state blood level so that the EKG measurement of your QT interval is meaningful:

"this much N adds/(does not add) to my interval".

Nothing else will handle the "sudden death" side effect.
And--
Only long-term use will give results.

Sooooo.....the on/off stuff :

1. just confuses the issue,
2. endangers your life with an unknowable (fluctuating) blood level of N that therefore cannot be meaningfully related to your QT interval, and
3. puts off the actual beginning of therapy and finally
4. puts off the results you are taking it for!

*************************************************************

So the only reasonably safe way to approach it is to:

1. Take enough time before beginning again to process any accumulation. Start at zero.
2. Choose a 1x /da dose (25 mg.?)
3. After a month or so, get an EKG.

There are a lot of unknown genetic factors in how YOUR QT interval responds to N.
There is no substitute for the EKG--without it,

Nilotinib is unsafe at any dose,

---no matter how small.

It is unlike any drug we could ever encounter any other way and less than 10% of how individuals (and their hearts) vary in response to it is even known***....

So
every person has to test the effect of every dose on their heart, and keep testing the same dose over time as therapy continues because ANY dose can accumulate and many (unknown) factors about the individual can change.


***This is what scares your Neurologist.

He can't balance the (mostly unknown) risk of your life against the known traditional Parkinson's meds that are safe and working for you right now.

[splib]

Hi Library, unfortunately without support from your doctor/neurologist (and it seems very few are willing to support taking it at this time), how do you propose getting a regular EKG?

 

> He can't balance the (mostly unknown) risk of your life against the known traditional

> Parkinson's meds that are safe and working for you right now.

 

The problem is that these traditional meds you mention are absolutely not working to prevent the progressive brain damage that's going on. Like 0% effective, no use at all, might as well not even mention them.

 

I see the balance more like take a tiny risk now on one hand versus guaranteed brain damage on the other hand.

 

I would think that some regularly scheduled off times should deal with the N accumulation issue very effectively. Maybe something like 3 weeks on, 1 week off would tune it more for therapy. More frequently interspersed days off would tune things more for safety at the expense of therapy.

 

Or another possibility could be tiered dosing like full dose for 2 days, half dose 2 days and then 1 day off, take a full week off every 10 weeks.

 

Anyway, if N is definitely going to accumulate on a standard daily dosing scheduling, is it really the best idea to rely on an abnormal EKG as the sole indicator of when you're in trouble and need to take a break? Why not have an approach that is likely to avoid the abnormality from happening in the first place?

 

splib

 

[stefan_001]

This looks interesting, not about N but this seems to be the most relevant thread:
Inhibition of 12/15-lipoxygenase activated autophagy, the body's natural kill system for cells. The activation was associated with decreased levels of tau, suggesting that the inhibitor works by re-activating the neuronal autophagy machinery to clear cellular buildup of tau.
https://www.scienced...70105100948.htm

[MarcB]

Hi Library, unfortunately without support from your doctor/neurologist (and it seems very few are willing to support taking it at this time), how do you propose getting a regular EKG?

 

> He can't balance the (mostly unknown) risk of your life against the known traditional

> Parkinson's meds that are safe and working for you right now.

 

The problem is that these traditional meds you mention are absolutely not working to prevent the progressive brain damage that's going on. Like 0% effective, no use at all, might as well not even mention them.

 

I see the balance more like take a tiny risk now on one hand versus guaranteed brain damage on the other hand.

 

I would think that some regularly scheduled off times should deal with the N accumulation issue very effectively. Maybe something like 3 weeks on, 1 week off would tune it more for therapy. More frequently interspersed days off would tune things more for safety at the expense of therapy.

 

Or another possibility could be tiered dosing like full dose for 2 days, half dose 2 days and then 1 day off, take a full week off every 10 weeks.

 

Anyway, if N is definitely going to accumulate on a standard daily dosing scheduling, is it really the best idea to rely on an abnormal EKG as the sole indicator of when you're in trouble and need to take a break? Why not have an approach that is likely to avoid the abnormality from happening in the first place?

 

splib

 

Seems like an ECG is essential, so before I'd speculate about dosing strategies, I'd try to figure out how to get ECGs. Try different doctors.   Many of them who don't approve of our research are doing ECGs.

 

Pay a clinic for an ECG and pay another doctor to interpret it.   I had to tell my neurologist, "You don't get to withhold health care 'cause you don't approve of the life choices a person makes.  If someone comes  to you addicted to opiates, do you get to deny them  health care?"  I go to the VA, so maybe they don't have the freedom others do, but it feels like refusing tests violates their oath.  A doctor who refuses ECGs that would keep you alive is more concerned with protecting him/herself than protecting you.
 

[David Watford]

Hi David, but do you think you've had any positive effects on PD symptoms from the Nilotinib ?

 

re:

> And something else which I can’t remember.

 

Probably Inosine ? There's a trial currently for that, you have to be careful not to ramp it up too high though because it can cause kidney stones or gout. The other thing not on your "influencers" list there is exercise or were you talking pharmaceuticals only maybe. Exercise and inosine kind of go well together, as far as I know the reason why inosine is readily available as a supplement is because it's used by people in intensive exercise regimens. But I think the trial is trying to show a potential slow down of progression, not really big changes.

 

re:

> Smoking

 

Well, for the case of using it as a therapy you use the transdermal patches, not actual smoking because you don't want to get lung cancer. This seems pretty promising because there's a big negative correlation between smokers being significantly less likely to get PD than non smokers. There's a French neurologist who has been pursuing this for a while now it seems, the main source of information I've seen on it is this discussion thread here: https://www.neurotal...ines-magic.html .

 

I've been focusing on exercise 1hr a day and I've been doing the nicotine patch protocol for about a year now, I think the nicotine is helping but it's pretty difficult to say for sure because I'm early stage young onset which often has a slow progression anyway. But a few times that I've forgotten to put on a new patch (or patches now, I put on 2 of them now) I've had bad days which I think is an indication it's doing something.

 

Another one that I had some high hopes for is TUDCA: http://forum.parkins...ew-drug-for-pd/ but it didn't seem to do anything for me and did not agree with my digestion.

 

I also tried Low Dose Naltrexone for about a year but I decided it wasn't giving me any noticeable results so I stopped that. Also tried CBD for a while but not any luck there either for me anyway, I've thought some about higher doses.

 

Some other supplements that I take in the hope of just general brain health are Citicoline+Uridine+DHA , low dose Lithium Orotate, and recently started Xanthohumol+hops, Lion's Mane mushroom extract, and Ashitaba tea.

 

Also I just started Rasagiline 0.5mg a few months ago since I found a cost effective Indian manufactured version, there isn't consensus but it seems a lot of Neurologists think they showed evidence of slowing progression in the Azilect trials a while ago.

 

Then Nilotinib is next up to try.

 

splib.

 

Hello Splib,

I'll post my N dose history... but in the mean time...  A friend who hadn't see me for a month, said to me last night... "Do you feel as good as you look?" I was delighted. Several people have commented on the improvement. But, ever cautious, I am cautious that some of them may be witnessing an improvement over the whole of the last year from starting on Western LDOPA meds. Most of the comments have come in the last couple of months.

 

My post

 

http://www.longecity...ndpost&p=795067

 

has my neurologist's report from November with the clinical findings with the reduction in disability scores.

It mentions the possible random variation . I am going to get another test done in a fortnight (3 months).

But things are improving.. especially with concentration (hence I am replying to you now),  typing (faster today than before and with fewer mistakes), smelling (a little bit), general alertness.

I still tire quite easily, which has been hard to observe rationally because it's muddled a bit by the fatiguing effects of N.

However, my impression is that the N is working. I'll let you know if I change my mind!

 

Exercise... ABSOLUTELY!...mostly swim 300m 2-3- times per week 1 hour of Hatha yoga 2 times per week. However, on occasional weeks, nothing - due to being away at work ( I work intermittently as a director/minnion for a software company) or holiday (e.g. last week). I'm thinking of getting the table tennis table out again for some rapid reaction stuff. (They say that fast things like punching are good.) Owing to a dodgy ankle, walking is a bit hit and miss for me.

 

 

[David Watford]

If accumulation is a problem, processing has been too slow--so you would need more time for your (inadequate!) CYP enzymes to catch up. I'd give at least a couple weeks and a month would be better.

The on/off dosing schedule is not a good idea because it confuses the EKG results --- since you don't know what blood level you are getting when, it can't tell you if you are ok or not.

*****************************************************************
WHAT YOU REALLY NEED

N is a long-term therapy so what you really need is to find what dose you can stick with and achieve a steady-state blood level so that the EKG measurement of your QT interval is meaningful:

"this much N adds/(does not add) to my interval".

Nothing else will handle the "sudden death" side effect.
And--
Only long-term use will give results.

Sooooo.....the on/off stuff :

1. just confuses the issue,
2. endangers your life with an unknowable (fluctuating) blood level of N that therefore cannot be meaningfully related to your QT interval, and
3. puts off the actual beginning of therapy and finally
4. puts off the results you are taking it for!

*************************************************************

So the only reasonably safe way to approach it is to:

1. Take enough time before beginning again to process any accumulation. Start at zero.
2. Choose a 1x /da dose (25 mg.?)
3. After a month or so, get an EKG.

There are a lot of unknown genetic factors in how YOUR QT interval responds to N.
There is no substitute for the EKG--without it,

Nilotinib is unsafe at any dose,

---no matter how small.

It is unlike any drug we could ever encounter any other way and less than 10% of how individuals (and their hearts) vary in response to it is even known***....

So
every person has to test the effect of every dose on their heart, and keep testing the same dose over time as therapy continues because ANY dose can accumulate and many (unknown) factors about the individual can change.


***This is what scares your Neurologist.

He can't balance the (mostly unknown) risk of your life against the known traditional Parkinson's meds that are safe and working for you right now.

 

Dear Library,

I am using the endearment deliberately.

This is an open letter to thank you for your careful (and caring) attention to this topic and its members.

It is great guidance.

I'll reply more fully to your post later,but in the mean time....thank you.

Cheers

David

[splib]

Hi David, thanks very much for posting your information, sounds like it's going well!

 

And @Library, please don't get me wrong I also greatly appreciate the information you have posted as well, thank you!

 

splib

 

[Logic]

Group Buy round 4 progress report:

 

The lab has tested the N and found it to be as advertised.
The package has been split up and should be posted tomorrow afternoon.
I will send everyone their tracking #s as soon as I receive them.

 

My apologies for the lack of posts and slow progress:  Once the package gets to the lab 'things take as long as they take' and worry that nagging may P then off...

 

Power cuts are wreaking havoc on my post atm.  I will post more later.

Edited by Logic, 24 January 2017 - 11:33 AM.

[Library]

Hi Library, unfortunately without support from your doctor/neurologist (and it seems very few are willing to support taking it at this time), how do you propose getting a regular EKG?

> He can't balance the (mostly unknown) risk of your life against the known traditional
> Parkinson's meds that are safe and working for you right now.

The problem is that these traditional meds you mention are absolutely not working to prevent the progressive brain damage that's going on. Like 0% effective, no use at all, might as well not even mention them.

I see the balance more like take a tiny risk now on one hand versus guaranteed brain damage on the other hand.

I would think that some regularly scheduled off times should deal with the N accumulation issue very effectively. Maybe something like 3 weeks on, 1 week off would tune it more for therapy. More frequently interspersed days off would tune things more for safety at the expense of therapy.

Or another possibility could be tiered dosing like full dose for 2 days, half dose 2 days and then 1 day off, take a full week off every 10 weeks.

Anyway, if N is definitely going to accumulate on a standard daily dosing scheduling, is it really the best idea to rely on an abnormal EKG as the sole indicator of when you're in trouble and need to take a break? Why not have an approach that is likely to avoid the abnormality from happening in the first place?

splib

[Library]

The EKG is the sole indicator for N in your body because the QT interval lengthening is the side effect that will kill you. It is what makes N a very dangerous drug.

About 30% of people are susceptible and nobody can tell who it is. All anybody can do is :

1. avoid other interval-lengthening drugs (effects are additive) and
2. avoid drugs competing for 3A4 that will uplevel the bioavailable dose. And then --
3. test regularly to see if N is increasing your baseline interval.

It doesn't take much of a change in the interval to kill you. It happens suddenly and there is no rescue. So you have to watch that interval like a hawk.

Nobody ever expected that somebody would be able to get their hands on a chemo drug without MD specialist supervision. Hopefully one of us will figure out how to get the necessary regular EKG's.

But for the first one, most any General Practitioner (all?) would give you an EKG for a family history of heart disease or your complaint of pain or a fluttering feeling in your chest.

Does anybody have experience with the little $100 EKG monitors online? I can't tell if they give the QT interval or not.

--Library

[mlsirkis]

Georgetown update.

Attached Files

•  Nilotinib PD Research Updates January 2017.pdf   127.7KB   41 downloads

[David Watford]

I found this list of QT interval prolonging drugs.

Imatadine is on it (for Parkinsons) I have been on this  for a decade now, along with the Aryuvedic medicines ) for years(I forgot to say this in my previous post)
So I will be coming off this as well.

Attached Files

•  QT interval Prolonging Drugs.pdf   377.88KB   11 downloads

[niner]

If you're using Nilotinib, I'd recommend taking a look at the manufacturer's Package Insert.  This is what the doctor is supposed to read before prescribing the drug. 
 
Some highlights:
 
Normal dosage:  600 or 800mg/day, in two divided doses 12 hours apart.
 
Clinical trial experience:  

 

300mg twice daily, 279 patients:
 
"Increase in QTcF greater than 60 msec from baseline was observed in 1 patient (0.4%) in the 300 mg twice daily treatment group. No patient had an absolute QTcF of greater than 500 msec while on study drug."

400mg twice daily, 458 patients:

"Sudden deaths and QT prolongation were reported. The maximum mean QTcF change from baseline at steady-state was 10 msec. Increase in QTcF greater than 60 msec from baseline was observed in 4.1% of the patients and QTcF of greater than 500 msec was observed in 4 patients (less than 1%)"
 
All Trials:
 
"Sudden deaths have been reported in 0.3% of patients with CML treated with nilotinib in clinical studies of 5,661 patients."

 
All of the adverse effects of the drug appear to be dose-dependent.   At these doses, a steady-state plasma concentration was reached by day 8 of continuous dosing.  At lower doses, a lower steady-state concentration is reached.   The plasma exposure at steady-state is approximately double the plasma exposure at day 1, with once daily dosing.  Dosing twice daily increases exposure substantially (3.8x) despite taking an identical total dose daily .  The systemic exposure to the drug is increased 82% if it is taken 30 minutes after a high-fat meal.  It is recommended that it be dosed on an empty stomach, meaning no food two hours before or one hour after dosing.  You should avoid strong CYP3A4 inhibitors while taking it.  Hypokalemia and hypomagnesemia are risk factors.  (You may want to supplement potassium (or bananas) and magnesium.)   It is recommended that you get an EKG at baseline, then at steady state.  (at least a week)  Standard liver function, blood count, and electrolytes should be done at 2 weeks.  At the high doses used here, they recommend a CBC every 2 weeks for the first two months, then monthly.  At low doses, that is likely to be overkill.

 

 

[richard hnry]

I have a question.  If N works by breaking down alpha synuclein ( at least a little bit) and this increases dopamine according to the study- If this is the mechanism for improving symptoms, then if a treatment were to come along that was very effective at removing nearly all of the alpha synuclein like M13 does from Neurophage would that mean all of the PD symptoms would go away or at least in large part?

[splib]

@richard hnry - the simplest explanation I've seen so far is here:

https://www.michaelj...g-for-parkinson

 

From what I understand N does not itself directly break down alpha synuclein, what it does is inhibit c-Abl. If you have too much c-Abl it prevents parkin from doing it's job properly.

 

Hopefully the N will get parkin back behaving normally and that's what will get rid of some alpha synuclein.

 

For improving symptoms I would guess the mechanism there are with cells that are not totally dead yet but are malfunctioning are getting rescued. Probably something along those lines anyway, unless it's placebo effect.

 

For the next wave of stuff that targets alpha synuclein more directly like PRX002, etc.. I think the hope there is that it removes nearly all of the alpha synuclein from your bloodstream , not from every spot in your body entirely. But hopefully removing it from the blood would then stop the progression, that's the next big treatment stage that will hopefully happen. If progression can be halted then maybe after that malfunctioning cells can be rescued for some improvement and then nobody knows if some cells are just dead and beyond being rescued. If a bunch of them are goners then you're going to have to grow new ones for all of the PD symptoms to go away.

 

I wonder though if once progression is stopped if DBS will then become a true cure for motor symptoms, I mean if the DBS won't wear off over time anymore.

 

A lot is still unknown but it sure seems like they're zeroing in on it much better.

 

[richard hnry]

@richard hnry - the simplest explanation I've seen so far is here:

https://www.michaelj...g-for-parkinson

 

From what I understand N does not itself directly break down alpha synuclein, what it does is inhibit c-Abl. If you have too much c-Abl it prevents parkin from doing it's job properly.

 

Hopefully the N will get parkin back behaving normally and that's what will get rid of some alpha synuclein.

 

For improving symptoms I would guess the mechanism there are with cells that are not totally dead yet but are malfunctioning are getting rescued. Probably something along those lines anyway, unless it's placebo effect.

 

For the next wave of stuff that targets alpha synuclein more directly like PRX002, etc.. I think the hope there is that it removes nearly all of the alpha synuclein from your bloodstream , not from every spot in your body entirely. But hopefully removing it from the blood would then stop the progression, that's the next big treatment stage that will hopefully happen. If progression can be halted then maybe after that malfunctioning cells can be rescued for some improvement and then nobody knows if some cells are just dead and beyond being rescued. If a bunch of them are goners then you're going to have to grow new ones for all of the PD symptoms to go away.

 

I wonder though if once progression is stopped if DBS will then become a true cure for motor symptoms, I mean if the DBS won't wear off over time anymore.

 

A lot is still unknown but it sure seems like they're zeroing in on it much better.

It does look like the N does target the alpha synuclein by whatever mechanism and that reduction is what is increasing dopamine and improving symptoms.

 

https://www.ncbi.nlm...ubmed/23666528 

 

So, if there is a treatment like M13 from neurophage http://www.pbs.org/w...lzheimers-cure/ would clear out the alpha synuclein we should get some relief of symptoms I hope.

[Logic]

Round 4 Progress report:

 

Everyone from round 4 should have received their tracking #s.  (Except khalidnt:  Address query from USPS)

If you have not; please contact me.

 

Most researchers in the USA should receive their packages today.
I wish everyone all the best in their research and advise everyone to read Niner's post and to take the necessary precautions.

Niner is a highly respected ex moderator and mentor  (See his post count and thankyou points...) and has done an excellent job of addressing the QT interval/heart attack concerns that have been overblown somewhat here recently, IMHO.

All I can add is to look at the BHT posts and research posted here if you are interested in the upregulation of CYP3A4 and the disruption of the lipid layer of many of the viruses associated with dementias.

 

I will post the Lab's mass spectrography report as soon as I get it.
The Dr. is still writing it up (busy), but says its more of the same.  ie: Its of the same high purity and quality as the previous batches.

 

 

Edited by Logic, 27 January 2017 - 01:06 PM.

[Logic]

If you're using Nilotinib, I'd recommend taking a look at the manufacturer's Package Insert.  This is what the doctor is supposed to read before prescribing the drug. 
 
Some highlights:
 
Normal dosage:  600 or 800mg/day, in two divided doses 12 hours apart.
 
Clinical trial experience:  

 

300mg twice daily, 279 patients:
 
"Increase in QTcF greater than 60 msec from baseline was observed in 1 patient (0.4%) in the 300 mg twice daily treatment group. No patient had an absolute QTcF of greater than 500 msec while on study drug."

400mg twice daily, 458 patients:

"Sudden deaths and QT prolongation were reported. The maximum mean QTcF change from baseline at steady-state was 10 msec. Increase in QTcF greater than 60 msec from baseline was observed in 4.1% of the patients and QTcF of greater than 500 msec was observed in 4 patients (less than 1%)"
 
All Trials:
 
"Sudden deaths have been reported in 0.3% of patients with CML treated with nilotinib in clinical studies of 5,661 patients."

 
All of the adverse effects of the drug appear to be dose-dependent.   At these doses, a steady-state plasma concentration was reached by day 8 of continuous dosing.  At lower doses, a lower steady-state concentration is reached.   The plasma exposure at steady-state is approximately double the plasma exposure at day 1, with once daily dosing.  Dosing twice daily increases exposure substantially (3.8x) despite taking an identical total dose daily .  The systemic exposure to the drug is increased 82% if it is taken 30 minutes after a high-fat meal.  It is recommended that it be dosed on an empty stomach, meaning no food two hours before or one hour after dosing.  You should avoid strong CYP3A4 inhibitors while taking it.  Hypokalemia and hypomagnesemia are risk factors.  (You may want to supplement potassium (or bananas) and magnesium.)   It is recommended that you get an EKG at baseline, then at steady state.  (at least a week)  Standard liver function, blood count, and electrolytes should be done at 2 weeks.  At the high doses used here, they recommend a CBC every 2 weeks for the first two months, then monthly.  At low doses, that is likely to be overkill.

 

Thank you for your input Niner.

Niner is a highly respected and learned member and ex moderator on Longecity. (See his post count and thank you points) and I have learned a lot from him and value his input greatly.

 

I feel that, given the above facts, the current concerns about QT interval etc may scare away people that would benefit greatly from N use.  

The facts do not support the hypothesis that you can only take N for a short time before it builds up and kills you.

Especially at the much lower doses being used for PD etc.

Also see the BHT info here if you want to upregulate CYP3A4.

 

I would also like to thank mlsirkis who ended up being my eyes and ears in this thread while my attention has been on the Dasatinib group buy and automating the group buys more etc-etc, as well as other pertinent info like the attached Nilotinib PD update from Georgetown U. 

 

Attached Files

•  Nilotinib PD Research Updates January 2017.pdf   127.7KB   14 downloads

Edited by Logic, 27 January 2017 - 01:58 PM.

[Logic]

I'll post my N dose history... but in the mean time...  A friend who hadn't see me for a month, said to me last night... "Do you feel as good as you look?" I was delighted. Several people have commented on the improvement. But, ever cautious, I am cautious that some of them may be witnessing an improvement over the whole of the last year from starting on Western LDOPA meds. Most of the comments have come in the last couple of months.

 

Hello Splib,

 

My post

 

http://www.longecity...ndpost&p=795067

 

has my neurologist's report from November with the clinical findings with the reduction in disability scores.

It mentions the possible random variation . I am going to get another test done in a fortnight (3 months).

But things are improving.. especially with concentration (hence I am replying to you now),  typing (faster today than before and with fewer mistakes), smelling (a little bit), general alertness.

I still tire quite easily, which has been hard to observe rationally because it's muddled a bit by the fatiguing effects of N.

However, my impression is that the N is working. I'll let you know if I change my mind!

 

Exercise... ABSOLUTELY!...mostly swim 300m 2-3- times per week 1 hour of Hatha yoga 2 times per week. However, on occasional weeks, nothing - due to being away at work ( I work intermittently as a director/minnion for a software company) or holiday (e.g. last week). I'm thinking of getting the table tennis table out again for some rapid reaction stuff. (They say that fast things like punching are good.) Owing to a dodgy ankle, walking is a bit hit and miss for me.

 

 

Hello David

I am glad N seems to be working for you and am surprised at the low dosage that seems to be optimal for you.  Proof that everyone's different...

I would like to know your thoughts in the C60oo (powerful mitochondrially targeted antioxidant) I recommended you try as a means to offset the fatiguing effects of N plz?
Also the Resveratrol, Pterostilbene, Blueberry extract I recomended.

 

Everyone:
I find Logjam's post on Harmine interesting and would also like to hear anecdotal reports from anyone who has tried it.
http://www.longecity...downs-diabetes/

 

Also interesting, from a longevity POV is the 25% lifespan increase seen from increasing PARKIN/PINK1 and Atg1 by just the right amount:

http://www.longevity...chondrial-aging

 

Anyone interested in another N group buy; Plz post here.

[45rpm]

Here's some more information about Harmine.

 

http://www.movementd...-Vol-3-Issue-1/

[45rpm]

Targeting Parkinson's-linked protein could neutralize two of the disease's causes...

 

https://www.scienced...70201110632.htm

[richard hnry]

I have 100 grams of N from the 2nd group buy.  If anyone wants to buy it let me know and I will send it to you.

[MarcB]

Science Daily from Feb 8

 

https://www.scienced...70208131804.htm

 

[mlsirkis]

Georgetown study flawed?

Attached Files

•  Nilotinib Devil is in the details.pdf   30.73KB   74 downloads

[khalidnt]

Georgetown study flawed?

 

Could MAO-B Inhibitor Withdrawal Rather than Nilotinib Benefit Explain the Dopamine Metabolite Increase in Parkinsonian Study Subjects? 

 

It seems we are back to square one