steve, you won me over!

just curious,
what meds did you fine tune and what was the outcome?
that intrigues me, i stopped taking selegilene because it raised my BP and honestly, i can't notice any difference, might even feel better and i guess it would be interesting to quantify that. but one can assume that if you can't "feel" the difference, then who cares if the measurements show one?

and of course it would be useful when switching generics, to quantify the benefit so you can have some evidence that one generic might be worse than another and complain to your insurance company or the FDA. I'm on a roll here!

it also seems a lot of azilect is being prescribed to those just diagnosed, it WOULD be interesting to see if it really made any difference in a specific individual. of course, i assume one reason a lot of RX's are being written is the potential neuroprotective benefit.


and having a common measurement to compare the benefit of a supplement(s) would be very useful. how much do those pads cost?

Steve,

I suggest we do a trial trail before anyone goes out and buys a graphics tablet. (I have one already, a "Trust". Is this likely to come up to spec?) If that goes well, let's get other people involved.

soccertese,

You raise the issue of Azilect (rasagiline). It has no apparent effect on me. BUT ...

The literature reports that 1 mg of rasagiline is theraputically equivalent to 100 mg levodopa [1]. Now, 100 mg of levodopa (taken as part of Sinemet or Stalevo) would have a very noticeable effect on me.

How can those two positions be reconciled?

My hunch is that it's because the duration of rasagiline's effectiveness is so much longer. It is normal to take one rasagiline 1 mg pill per day, while Sinemet and Stalevo are often taken at 3 hourly intervals. So to get the same AOC (area under the curve) you need only one eighth (3 divided by 24) of the average impact. A dose of 12.5 mg of levodopa might not be noticed by many people, especially given all the other medications that we take. But that doesn't mean that the rasagiline is not "working".

(Interestingly, the difference is not in the main caused by rasagiline having a longer half life. An NIH archives document [2] states:

"Its mean steady-state half life is 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B."

I take that to mean that rasagiline comes in, does its job and departs, but that its effect carries on far longer:
"Studies in healthy subjects and in Parkinson's disease patients have shown that rasagiline inhibits platelet MAO-B irreversibly. The inhibition lasts at least 1 week after last dose." [2])

References

[1] "Levodopa Dose Equivalency", Claire Smith, 2010.
http://www.birmingham.ac.uk/Document...hLEDReview.pdf

[2] http://dailymed.nlm.nih.gov/dailymed...rchiveid=10668

John

your're right, it binds to MAO-B and inactivates it, how long it takes to replace that inactivated MAO-B obviously is more than a day.
i also mentioned that i stopped taking selegilene, an older irreversible mao-b inhibitor, and noticed no increase in pd symptoms after 2 weeks. so there must be cases in advanced pd'ers where azilect shows no improvement also.

and most people are starting azilect by itself.

Quantifying the short term effect on me of Stalevo dispersed in ascorbic acid (Vitamin C).

My recipe was very simple:
- put one Stalevo pill (75mg levodopa) in a glass;
- add 50ml water;
- add 1000mg effervescent vitamin C tablet.
Leave for 2 hours to disperse.

The attached graph shows the pharmacodynamics of the drink on me.

StalevoVitC.png

Side-to-side tap test results (high is good):

Baseline (4 readings).
Mean left = 14.34 taps, right = 12.95 taps

After taking the pill until return to baseline (15 readings)
Mean left = 25.28, right = 19.15
Max left = 32.08, right = 25.81
First minor effect seen 15 minutes after drinking the liquid.
First major effect seen after 40 minutes.
Peak reached after 70 minutes.
Back to baseline results after 150 minutes.
Correlation left/right = 0.960
The area under the curve and above the baseline (gives a measure of the drug's total effect) = 2570 taps.

Details.

To reduce the effect of my previous drug intake on the result, I started this experiment "off". This is difficult for me because I take some long acting medication, Requip XL and rasagiline. I was off these for 43 hours before starting. I was also off my fast acting medication, Stalevo, for 31 hours. This meant that, although not all the drugs had been washed out of my system, whatever was left was unlikely to have a large confounding effect on the result. Meals can also affect the results: I ate a large meal 7 hours before starting. Similarly, exercise can also affect the result, I was at my desk for almost the whole 3 hours 25 minutes that I ran the test.

To measure the results I used my online, side-to-side tap test program:

http://www.parkinsonsmeasurement.org...eToSideTap.htm

This measures the number of times you can type q followed by p in 30 seconds using just the index finger of one hand. It is done separately for each hand. I took 21 readings, one every 10 minutes, except there was 15 minutes between my last reading before taking the drink and my first reading after taking the drink.

In the table below times are in minutes. Negative times represent the period before the drug was taken. LH and RH denote the left and right hand, respectively. Taps refers to the number of q,p cycles done in 30 seconds using just the index finger of one hand.

Time,LH_Taps,RH_Taps
-35,16.98,12.83
-25,13.31,14.22
-15,12.60,12.61
-5,14.48,12.14
10,16.48,14.17
20,19.02,14.46
30,17.33,11.86
40,30.42,23.50
50,31.63,23.13
60,30.20,24.53
70,32.08,25.81
80,30.51,23.48
90,28.51,22.85
100,28.32,21.12
110,26.04,19.79
120,26.57,21.80
130,22.17,15.66
140,23.41,14.07
150,16.46,10.98
160,13.10,9.30
170,13.63,13.25

The source of the Vitamin C was a 1000mg effervescent tablet produced by Principle Healthcare. A tube of 20 tablets cost £1. Ingredients: citric acid, ascorbic acid, sodium hydrogen carbonate, sorbitol, polyethylene glycol, maltodextrin, aspartame, acesulfame, acacia, flavouring, coloring.

John

This is Very, Very interesting. I love attempts to qualify everything.

I want familiar with this test. The best I managed was 22.6 something. I had my wife take it, she managed 24s. I wonder how much effect practicing with frequent testing would have.

Hammilton,

You are absolutely correct: practice does improve your score.

The quantification of this learning effect is one of the objectives of an online survey and test that I'm running at:
http://www.parkinsonsmeasurement.org/PDMeasure

So far, 90 people have done the test a total of 200 times.

You're very welcome to take part.

It would be interesting to know whether all clinical trials make a large enough allowance for the learning effect.

John

I have, I did it a few times. I haven't tried it with l dopa in me yet. I try to take as little as I can. Unless the restless legs are horrible, I don't take it. I worry about compulsive behavior; given that I've had issues with self medication I try to minimize any meds but dopaminergics are especially prone to cause that.

I took some this afternoon expecting to give it a try and now tonight I'm having more problems than if I hadn't taken it.


Question: what is the average score for someone without neuromuscular pathology?

Your dedication to detail is inspiring! Do you know of melevodopa (methyl ester of levodopa)? It is routinely used in Italy, produced by Chiesi Farmaceutici in Parma and called Sirio (a soluble form of L-dopa with carbidopa). In other words - fizzy Sinemet. It is reputed to cross the blood-brain barrier more rapidly than the standard formulation. Search pubmed.com using the keywords “Sirio” and “Parkinson’s Disease” for a couple of studies. The Italian website Unioni Parkinsoniani also has some information on Sirio. Google Translate can be used for a rough English translation. It’s not expensive but officially only available in Italy. Keep up the good work.
Paul

I take the view that if we can measure our symptoms there is more chance of finding methods to improve our condition. This is especially true if we want to get the most out of levodopa. For many PwP levodopa is very effective most of the time, but some times its benefit is delayed or lost. We need to understand why.

Here we look at:
- delayed gastric emptying;
- timing of a second dose;
- measuring progression.

The rest of the post quantifies these effects and describes a simple way to analyse the data yourself.

We first plot a graph of our side to side tap test scores over time.

gastricEmptying.png

Conditions under which the data was collected

The measurements are made using:

http://www.parkinsonsmeasurement.org...eToSideTap.htm

This time we look at the uptake of both a first and a second dose.

The conditions under which the results were collected are similar to those described in Post 1. An exception is that the gap between when I last took medication and when I started the test was shorter (here the time since Stalevo was last taken was 12hr, and since Requip Xl and rasagiline 18hr). The gap was probably adequate to clear the exogenous levodopa, but not the slow release agonist. The shorter time between doses may partially explain why the average scores are higher than in Post 1. (There may also be a learning effect - I'm probably still learning to get better at the test. I suspect that in many clinical trials insufficient allowance is made for this effect, with the result that the improvements due to the learning effect are mistakenly put down to the placebo effect.)

Delayed gastric emptying

It takes the first dose approximately 50 minutes to have a definite effect. With the second dose, however, even after 90 minutes there was no definite response. At this stage I had a simple breakfast, cereal with milk. Presumably this forced gastric emptying, because a definite response is seen within 20 minutes of starting to eat.

Timing a second dose

I take my doses at 3 hourly intervals. It will be seen that in this case I was already losing functionality even before the second dose was taken at 180 minutes. Given the lag between taking the drug and it taking effect this was too late to avoid me going into an "off" state. (Fortunately for me this is not too bad: typing is very slow, but walking is still good.)

Measuring progression

Finally, does a comparison between the results from Post 1 and these results say anything about the progression of the disease in me? There is 18 months between the tests. In spite of this, at first sight the results appear better. But, there is so much "noise" - confounding issues - that the raw data is unlikely to tell the whole story.

The key to extracting the true message is to eliminate as much of the noise as possible. To do this, I note that taps are made, albeit slowly, even when the PwP is off medication and that this is likely to be due to residual dopamine production. Let's call these endogenous taps. Extra taps are made possible by the medication. Let's call them exogenous taps. The ratio:

endogenous taps / total taps

shows what proportion of the taps are due to the body's own resources as opposed to the medication. This is, I believe, a useful proxy measure of progression. A healthy person would not benefit from levodopa, so would get 100%. A person badly affected by PD would be unable to tap when "off" so would get zero.

The results that I have for the endogenous ratio are:
- 62.7%, 18 months ago (Post 1)
- 61.4%, 15 months ago (Post 11)
- 63.6%, now (this post)

My subjective opinion is that these figures reasonably represents my motor ability, but not my over all state, which has got worse in the intervening period.

John

It's been two years since I last posted in this thread. Let's see what's happened since.

Under similar conditions to those reported in previous posts - while "off" take 75mg Stalevo dissolved in vitamin C (details in the Appendix) - the speed that I can side to side tap was measured every 10 minutes over the course of a single drug dose.

StalevoVitC.png

The results show that my tapping speed has increased over time. The main factor behind this appears to be due to a faster tapping rate while "off", rather than an improved effectiveness of the drug.

While there are great statistical weaknesses with this one off test, the results are in line with my scores in other tap tests that I do. As has been mentioned before, I think the most likely reason for the higher score is that I am training myself to do better at this test. However, this raises an interesting question: when do positive test scores promote the testing program into being a therapy itself?

Appendix

Here lives dragons!

Results

Data collected on 19th August, 2016, starting at (T-20) 0630. Previous doses: of Stalevo 13 hours before this one; ropinirole CR and rasagiline 23 hours.

Baseline (3 readings). The set of results 2013 (Post #11) are in [].
Mean left = 22.26 [14.34] taps, right = 17.23 [12.95] taps

After taking the pill until return to baseline (15 readings)
Mean left = 31.78 [25.28], right = 22.88 [19.15]
Max left = 37.69 [32.08], right = 28.56 [25.81]
First minor effect not seen, I went abruptly from "off" to "on" [seen 15 minutes after drinking the liquid].
First major effect seen after 50 [40] minutes.
Peak reached after 50 [70] minutes.
Back to baseline results after 150 [150] minutes.
Correlation left/right = 0.977 [0.960]
The area under the curve and above the baseline (gives a measure of the drug's total effect) = 2125 [2570] taps. This figure can be interpreted as the number of extra taps that 75mg of Stalevo buys me.
Endogenous ratio 72% [61%]

Time,LH_Taps,RH_Taps
-20,22.02,17.92
-10,21.59,16.87
0,23.17,16.89
10,24.86,16.07
20,24.42,17.09
30,25.13,17.52
40,24.93,16.27
50,37.67,28.56
60,37.69,26.62
70,36.07,26.48
80,34.85,25.06
90,34.54,25.42
100,36.43,25.54
110,35.76,25.80
120,31.08,23.24
130,32.59,25.58
140,29.01,21.04
150,21.62,14.71
160,18.68,14.41
170,20.03,15.69
180,20.74,15.21
200,21.29,15.83

John