Trials and Retribution?: I have not... - Parkinson's Movement

Parkinson's Movement

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Trials and Retribution?

honeycombe3
honeycombe3

I have not posted for some time as more pressing matters have needed my attention. Those who remember past posts will be aware that I regularly involve myself in clinical trials.

Why clinical trials? There is no restriction on number of type of trial. I have been assessed for clinical and medical trials including trial procedures (surgical).

I ended up participating in 4 as I did not meet the trial criteria for the others.

I am becoming increasingly concerned at the.number of posts from newbies and others who mention/quote information which has its basis in trials and which is 'dropped into' the text.

For example discussion around around when to start taking meds. There is a wealth of information from trials on this topic, yet this is rarely referred to. My husband and I spent hours filling in 6 monthly questionnaires for 10 years so that fellow PwP could reap the benefits. The results are quite clear: if you decide that at some point during treatment you will need to use certain meds then the earlier you can do so the better. This supercedes the existing folklore that one should ' save' on use of meds earlier.

So much for trials. Retribution? What price the effects of not exploring a breadth of research information when diagnosed? We read some of them each time we access this site. People who have found that accepted wisdom is not all that it seems, that there is no '1 size fits all'. I am afraid that this post is much stronger than I had imagined. I put this down to 16 years PD, heart failure and arthritis!

54 Replies
oldestnewest

It has been very difficult to get people to understand that many many trials have all come to the same conclusion that delaying taking medication serves no purpose. The old school old wives tale information that Levadopa medication is somehow unnatural and that you should avoid and delay taking it, just will not go away . They come here at the very beginning just after diagnoses , all so proud of the fact that they have not taken the medication prescribed by their doctor and point out that they can still work etc. It catches up to them eventually and they hit the wall, but they do not write in . I have stopped trying to help them . They know so much more , they read a book. One women wrote that she was still keeping her husband off the prescribed medications and then went on to complain about his symptoms of depression . Then to add insult John will add his post and tell you again about fast walking and how no one needs to take medication anyway and how bad it is. Welcome back Honey.

One more thing, There is a group here now that believe that there is a giant conspiracy by the Drug Companies to only do research on deseaces that can make money (not PD ) but will shop regularly at the local health food store spending enormous sums of money on vitamins and supplements that the FDA does not even test let alone approve. Many testimonials here about the wonder of these supplements until enough other people try it with out similar results.

ChrisWF
ChrisWF in reply to GymBag

It is indeed ridiculous. Medicines that have been researched and are subject to at least some regulated quality controls are simply a plot to separate you from your money but supplements, which are neither (and are cheap as shit to make, by the way) are a smart way to spend your money and avoid being exploited. Bizarre.

Thank you for your dedication to research and the PD community! I'm wondering if you started meds immediately upon diagnosis? Have you tried anything else outside of medication? If so, that would possibly impact your questionnaire answers. Is that accounted for? If you haven't done anything outside of medication, your progression may be different from others who have incorporated things like qi gong, etc. I think it is up to the individual person to chose their own path. I don't take meds, but I also don't talk other people out of them. It simply is not my business. There have been MANY things touted as good for you by the FDA, etc that we find out later are not so. Trials (and manipulation of data) can show anything you'd like, so its important to keep that in mind when looking at research. I think it is healthy to look at all avenues for health....nutrition, exercise, sleep, stress, etc and make decisions based on improving them all. Medication has a place, lets allow each person to make their own decisions where that place is, without judgment. I'm sorry you are frustrated or disappointed. Your efforts are not in vain....we are all likely going to join you in the prescription world sooner or later. Hopefully later, with contributions to research like yours. I'm confident your years of experience with prescriptions will help our experience with medication be better. Much gratitude.

Hikoi
Hikoi in reply to NRyan

Ryan,

You have done exactly what Honeycombe is concerned about. You have dismissed the evidence claimed it may be inaccurate or falsified by various means and instead follow a non research approach and in so doing encourage others to do likewise.

Honeycomb wrote:

“.... discussion around around when to start taking meds. There is a wealth of information from trials on this topic, yet this is rarely referred to. My husband and I spent hours filling in 6 monthly questionnaires for 10 years so that fellow PwP could reap the benefits. The results are quite clear: if you decide that at some point during treatment you will need to use certain meds then the earlier you can do so the better. This supercedes the existing folklore that one should ' save' on use of meds earlier.“

Here is another example by smittybear. I’m sure he will get plenty of alternative treatments which are not going to help but I have learned there is no point in explaining that with research links.

healthunlocked.com/parkinso...

Cons10s
Cons10s in reply to Hikoi

Honeybear states in her bio that they are thankful for the support they received during their first two years with alternative treatments. Sounds like the pot calling the kettle black.

MBAnderson
MBAnderson in reply to Hikoi

Hikoi,

Let me ask you (and honeycomb) the question this way. Salvation1 is young onset and as you pointed out very recently he is more at risk of dyskinesia than I am and as you've also pointed out, ill effects of levodopa are dependent on dose not duration.

Therefore, should Salvation1 be mindful of what you said by trying to keep his dosage low, that is, should he try to get by with as little as possible?

marc

Hikoi
Hikoi in reply to MBAnderson

Aaah Marc

The study shows that it is not only the amount of levadopa that is the factor though that is a consideration ie after 13 years of treatment I now have dose dependent dyskenesia. if i take too much levadopa i get mild dyskenesia but if my dose is smaller I dont have it.

What convinces me is the finding that it is disease duration that is THE significant factor. This has been confirmed in the experience of a poster who had dyskenesia from the start of her levadopa treatment.

We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopa daily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified.

As to your question, YES, we all should be trying to keep our dosages as low as is practical.

MBAnderson
MBAnderson in reply to Hikoi

Thank you for answering my question.

I don't see how the "Hence..." follows from the previous sentence. I don't see the connection. I think it follows much more logically to say, "Hence, one should take as low a dose as possible."

I believe it supports the conclusion there is reason to delay because since it is dose that induces dyskinesia, reducing the dose reduces the likelihood of dyskinesia.

Taking no levodopa is the same strategy as taking as little as possible, it is just a different degree. It is the same management strategy with the goal to reduce and/or delay the likelihood of ill effects -- which is all I've been saying?

Hikoi
Hikoi in reply to MBAnderson

The section in bold is taken from the study conclusion. I didnt write it.

Again you ignore the disease duration effect which is the significant finding. Doesnt matter when you start levadopa that has no bearing on when you will get dyskenesia. When your disease has progressed to a certain level you will get side effects (if you are going to get them)

Reducing the dose by not taking any makes no scrap of difference according to the study and it does not delay onset of dyskenesia because the person will get dyskenesia at the same time whether they start levadopa early or late.

This is because the disease has progressed whether one takes levadopa or not. Levadopa cant be saved up. There isnt an amount taken after which time a person gets dyskenesia. If you are going to get dyskenesia at 4 years you will get it at 4 years and if one has held off taking meds for 4 years then you will have dyskenesia as soon as you start meds. Its severity will be according to dose of levadopa in 24 hours.

That is my understanding of the study and my observation.

MBAnderson
MBAnderson in reply to Hikoi

Hikoi, Thank you for the thorough explanation. I have to go back and reread the study.

PS. Doesn't this sentence, "If you are going to get dyskenesia at 4 years you will get it at 4 years and if one has held off taking meds for 4 years then you will have dyskenesia as soon as you start meds." make it sound like it's duration dependent?

Hikoi
Hikoi in reply to MBAnderson

You really dont want to believe the study findings do you.

As i said above i get mild dyskenesia which I dont notice and (nor would you i bet) when i go above about 800mg day. I am much more concerned about motor fluctuations.

From the paper

“During the past decade, a number of large drug trials suggested that the initiation of levodopa therapy should be delayed to reduce the risk of motor complications in patients with Parkinson's disease. However, the relative contribution of the cumulative exposure to levodopa and of disease progression to the pathophysiology of motor fluctuations and dyskinesias is still poorly understood. In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson's disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors.”

MBAnderson
MBAnderson in reply to Hikoi

Actually, not at all. I learn a lot from you and I appreciate that.

Apparently, I don't fully understand all the nuances of the study. I did not it understand it to conclude that if you're going to get dyskinesia after 4 years, you'll get dyskinesia after 4 years, even if you don't start levodopa until after4 years. That seems hard to fathom?

In other words, even a few doses of levodopa at the end of 4 years and you've got dyskinesia?? I can't help it, I just question that. Also, and more important, I don't see how that makes dyskinesia dose-dependent. (I haven't reread the study yet, but will do so shortly and will look for that explanation and data.)

ChrisWF
ChrisWF in reply to MBAnderson

After W years of disease, person X will experience Y levels of dyskinesia after taking Z levels of ldopa.

Plug in whatever values you like, noting that the value for Z is not influenced by how much ldopa person X has used in their lifetime.

MBAnderson
MBAnderson in reply to ChrisWF

I understand that. The study is saying the dosage is not cumulative. I accept that.

What I am having difficulty with is the example that a person who is destined to get dyskinesia in 4 years will get dyskinesia in 4 years whether they start levodopa at the time of diagnosis or one week before their 4th anniversary.

Okay. If that's what the study concludes, that's what it concludes and I either accept it or not. Give me little time to wrap my head around this.

MBAnderson
MBAnderson in reply to ChrisWF

Let me ask you and Hikoi one more question, then I'll quit.

What you're saying is that a person who is destined to get dyskinesia in 4 years because of the pathophysiology of the progression at that point, any amount levodopa introduced at that point will trigger dyskinesia (so if it provides relief, you might as well take it early on?)

jeffreyn
jeffreyn in reply to MBAnderson

No, it is dose-dependent relative to the number of dopamine neurons you have left.

Note that choosing a lower levodopa dose does not lower the rate of loss of your dopamine neurons.

MBAnderson
MBAnderson in reply to jeffreyn

That helps. Thanks.

jeffreyn
jeffreyn in reply to MBAnderson

In my own case, I started to experience (dystonic) dyskinesia just a few months after diagnosis, immediately after my neuro increased my levodopa dose from 100mg 3/day to 200mg 3/day. The dyskinesia stopped happening when I changed the schedule to 100mg 6/day.

MBAnderson
MBAnderson in reply to Hikoi

I'm sorry to hear you got dyskinesia now. If you don't mind my asking, what is the dosage that triggers it? On one hand you may feel good that it took 13 years, yet on the other hand, you still got it. How problematic is it?

Since we are all such snowflakes, I bet there are some people who get dyskinesia based on duration (and with others where it's a combination of both dose and duration.)

Plus, we know that any PWP can get dyskinesia from any dose at any duration. (There is a person on this forum who said she got dyskinesia from her 1st dose.)

NRyan
NRyan in reply to Hikoi

Yikes! I have not encouraged anyone in my post to take another path from medication. I clearly state our path is ours alone. There is research with various other things like exercise, sleep, etc. and their impact on PD. Anyone in the medical/research/science/mental health community knows that stats can show what you want them to show. The research coming from reputable sources is critical. That is all I meant. I am not questioning specific studies related to medication. I am questioning who is doing the research and what do they have to gain by this research subject! I could give a happy rat's ass who is taking meds. No one should care what I do with my own PD journey. Life is stressful enough, let's focus on what we share....not who is right or wrong. I love hearing all the experiences from everybody on this site.

Cons10s
Cons10s in reply to NRyan

Honeybear states in her bio that they are thankful for the support they received during their first two years with alternative treatments. Sounds like the pot calling the kettle black.

The vast majority of PWP take pharmaceuticals, consider them essential and are very well served by them, and I totally support that position, but what I don’t understand is why is there this belittling and disdain from the people who advocate taking pharmaceuticals from the time of diagnosis for people who choose not to and instead focus on complementary and alternative therapies?

It is not arguable that a compound that has not been recognized by the FDA as effective does not mean it is not effective. Citing the absence of FDA regulation on supplements doesn’t speak to their effectiveness. (It speaks to the quality control.)

Personally, I believe PWP might benefit from viewing supplements as a subset of nutrition and it is not arguable that a person’s nutrition or lack thereof affects progression.

There are studies which conclude that one third of all Canadians are deficient in vitamin D. Trying to make the case that supplements are not effective is exactly the same as making the case that having proper stores of vitamin D or B12 is not important.

Parkinson’s causes other illnesses, sleep disturbance, nutritional deficiencies, hormonal, enzyme, and micro-biome imbalances, and as these conditions accumulate and worsen, they often cause the progression to accelerate which worsens these conditions creating a feedback loop

Supplements can be transporters, inhibitors, co-factors, precursors, substrates, chaperones, inducers, amino acids, proteins, enzymes, hormones, metabolites, etc.

Please don’t misinterpret this. This is not a statement that people should not take pharmaceuticals from the time of diagnosis.

I am simply pointing out that there are millions of delicately balanced, complex molecular interactions and processes taking place continuously throughout our body that are necessary for optimal health and many of those molecules involved cannot be synthesized internally and can only obtained by ingestion.

Therefore, the functionality and efficiency of every single process in our body and brain is determined and limited by what compounds and foods are available for those molecular processes to interact with, that is, which molecules come down the gullet -- and the likelihood that any PWP has no deficiencies is zero.

PS. To state this much more briefly I don't feel it should be cast as either it is pharmaceuticals or supplements, but too often it feels like the pro pharmaceutical cohort feels the need to claim supplements are valueless.

ChrisWF
ChrisWF in reply to MBAnderson

I think you have missed the mark.

This is by some margin the most accepting PD forum on the internet when it comes to 'Alternative therapies'. I don't believe that naturalists (or whatever) are persecuted here at all.

What's ridiculous is when a new member joins, often describing material quality of life concerns (or their partner is suffering from same) and gets hit not only with a barrage of 'alternative therapies' that are rigorously promoted as being a substitute (not a complement) for meds, but are also exposed to a good deal of anti meds rhetoric (much of which is nonsense).

I don't think I've ever seen anyone be negative here about people encouraging others to try complementary therapies unless they are doing so in a fashion that is misleading.

Despe
Despe in reply to ChrisWF

Wow! Why don't you tell us about your pharmaceutical protocol? Is there one???

Hikoi
Hikoi in reply to Despe

Yes I would think every country has their own protocol for pharmaceuticals for PD.

Despe
Despe in reply to Hikoi

Sorry, Hikoi, but I asked ChrisWF, not you.

Hikoi
Hikoi in reply to Despe

Oh dear!

We are both from the antipodes will that do ☺️

MBAnderson
MBAnderson in reply to ChrisWF

I think when somebody's symptoms are problematic, they should talk to their doctor.

I have not ever made recommendations against pharmaceuticals. If anything I've encouraged their use.

I do encourage people to explore alternative therapies, while the whole point of Gym Bag's comment with which you concur is to denigrate alternative therapies, which I find curious, because as you know, some alternative therapies do affect progression where as no pharmaceuticals do.

Tell you the truth, if, when I were newly diagnosed, I knew then what I know now, I would've been more aggressive initiating alternative therapies and I am quite confident that would have allowed me to delay my starting levodopa later that I have.

I am perfectly happy with my decision to delay pharmaceuticals for as long as possible and to use them as sparingly as possible.

Bottom line; some alternative therapies slow the progression in some people while no pharmaceuticals do and people who are newly diagnosed should know that, too.

laglag
laglag in reply to MBAnderson

This is my opinion which I just posted on another post...(it kinda goes with what you're saying MBA)

I've been thinking about your question for a few days and decided to respond again. Do you know anyone that has been cured of Parkinson's using an alternative method? I don't think anyone can say they have been truly cured. I believe there are a lot of supplements and exercising you can do to slow it down a bit but I don't believe anything right now will cure it. Not to say there never will be. We can only hope and pray there's something in our lifetime. Not to be a "Debbie Downer" but it would be a good idea if they knew what causes it before they can fix it. It seems they have a lot of ideas, like dopamine, mitochondria, blood brain barrier, etc, etc, but they are not quite there yet. This site is the best thing to come to for ideas and opinions though. I have faith that someone on this site will help or be the one to figure it out.

So to end my lengthy opinion, you need to do a little bit of meds, a medium amount of supplements (which includes nutrition) and a lot of exercising (high intensity or at the very least keep moving and keep off the sofa). The meds and supplements will relieve some of your symptoms and will enable you to exercise longer and more often.

Also, stay away from stress if it's at all possible)

MBAnderson
MBAnderson in reply to laglag

For those who are dismissive of alternative and complementary therapies, it's not me they are refuting. It is the likes of Dr. Dale Bredeson and his counterpart in Parkinson's Dr. Laura Mishley. Dr. Bredeson is unequivocal and provides documented case studies asserting that his alternative therapy not only delays the onset of Alzheimer's, but reverses it. Likewise, if alternative and complementary therapies don't slow the progression, then Dr. Laurie Michley is misrepresenting her data.

Actually, the data is so overwhelming, it's a silly discussion to even have. It's comparable to disagreeing over whether not the sky is blue.

Further, each time I've had this discussion people, they raise the sub-Saharan African study and point out it's not the duration of levodopa therapy, but the dosage the cause the consequence. Accepting that premise, if it is the dosage that induces dyskinesia and not the duration, then reducing the dosage would forestalls the consequences of either dyskinesia or loss of responsiveness.

The example would be, a person is diagnosed and begins levodopa therapy starting at 3 per day and 10 years later is at 1400 mg per day and is experiencing either dyskinesia or loss of responsiveness. If that same person delays the initiation of levodopa therapy by 1 or 2 years because at the time of diagnosis there symptoms were not problematic and then over the course of the following 8 years averaged a lesser dosage, then consequences would show up later.

If over whatever time, it takes 10 pounds of levodopa to induce consequences, then if those 10 pounds are consumed in 5 years or 10 years, doesn't matter if it is dosage that will determine when the consequences occur.

I take as little levodopa as possible for the purpose of extending its useful life and I practice a robust regime of alternative and complementary therapies to extend my useful life.

laglag
laglag in reply to MBAnderson

MBA, I couldn't tell but I hope you didn't misread my reply as being against you?? I was basically agreeing with your reply to Chris.

ChrisWF
ChrisWF in reply to MBAnderson

This is not the first time that you seemed to have taken general comments personally. No one here has suggested that *you* have done anything. I think most here would agree that your views about PD management are balanced and sensible.

There have been several threads lately where people have been promoting strong anti med views, with the suggested alternatives being evidenceless nonsense.

MBAnderson
MBAnderson in reply to ChrisWF

Thank you. I agree.

laglag
laglag in reply to ChrisWF

I agree also.

Hikoi
Hikoi in reply to MBAnderson

as you know, some alternative therapies do affect progression where as no pharmaceuticals do.

No Marc that piece of info seems to have bypassed me. I dont know any studies that prove that, only hearsay. But I am happy to be proved wrong.

Dr Bredesen I believe has no randomised control studies. He says why not do his protocol while waiting for more robust evidence but, his treatment is very expensive and quite burdensome. I will do more searching.

MBAnderson
MBAnderson in reply to Hikoi

Exercise and nutrition are both alternative therapies. Are you believing that neither those effects progression??

ChrisWF
ChrisWF in reply to MBAnderson

Exercise isn't alternative, Marc. Most neuros and probably all MDS promote the shit out of it. It has been the subject of peer reviewed studies. I.e it is effectively proven (not really quantified yet, but proven in principle).

Nutrition Is a little bit different. I believe even LM is a little bit guarded about claiming that her diet definitely slows the progression of PD. In her 2017 paper she says dietary choices "may" influence progression.

In any event, the type of 'alternatives' that some of us would prefer see less often promoted to new members are pdrecovery.org and fast walking (fast walking as a substitute for meds rather than as a complement).

MBAnderson
MBAnderson in reply to ChrisWF

Chris,

You're not implying that there is no hard data that variations in diet affect health - are you?

PS Or, put another way, can reconsider vitamin D and B12 supplements nutrition?

MBAnderson
MBAnderson in reply to ChrisWF

A-a-a-a-ah, pdrecovery.org. I stumbled across them years ago and have completely forgotten about them. I put them in the same category as the medical medium Anthony Williams (celery juice man) who began getting medical advice from "the spirit" at age 4. Ever meet a 4-year-old that can explain what psoriasis is.

Quackamoles - both.

I totally agree there is far too much complete, utter fraud & nonsense on the Internet and too many newly diagnosed PWP gets sucked into it, waste their money and displace time that could have been better spent - only to have their hopes dashed.

And we should guard against it.

MBAnderson
MBAnderson in reply to Hikoi

I don't feel it is a practical standard for PWP to apply.

If every PWP waited for a placebo controlled study to act, there would be precious little to do except take pharmaceuticals. I feel that position is taking the easy way out because you know perfectly well there never be those kind of data produced for compounds that cannot be patented.

Dr. constantini and Dr. Jeanmonod don't have placebo-controlled trials, but lots of PWP have been beating their doors down trying to get access to their therapy.

In some situations, at some point anecdotes are worth paying attention to and often is a standard worth acting on.

PS. Lots of people on this forum have benefited significantly from high dosage thiamine.

I believe every 1 of them would say the anecdotal standard met their needs.

Parkie-
Parkie- in reply to MBAnderson

Very well said Marc. And I keep wondering why thousands of pwp would bother coming here if they felt their medication and their doctors support were optimal. I am also wondering why med advocates are coming here if their treatment is so satisfactory.

Despe
Despe in reply to Parkie-

Parkie,

Or some individuals could be moderators/reps of the pharmaceutical manufacturers. . .or they have nothing to do with PD. . . :)

Very well argued📌

Rather than having missed the mark as ChrisWF claims, I for one think these comments are on point.

But this is why I love this forum: there is always push back, which ideally, should lead to a balanced view point. 🌺✌🏾🌺

When I was first diagnosed, that’s the first thing I wanted to do. I got accepted to the DNL-201 trial. Phase 1. I got disqualified because I have the then unknown heart condition (called Wolf Parkinson white..... nothing to do with my PD) I wish I could, I hate this disease.

Aaaaaaaggh!! I just lost 20 minutes typing due to an involuntary spasm. I have asked Admin if drafts can be saved.

redhawk1
redhawk1 in reply to 38yroldmale

Hey 38yroldmale . . . in the coming year Biogen/Denali will be moving on to phase 2 using DNL151 and will most likely increase number of cohorts in trial and maybe relax exclusions. So, don’t give up hope. Have heard some positive vibes about this Denali medication. You are young and quite confident there will be some significant advances in treatments and disease modification in the next few years!!

Not everyone is capable of recognizing or absorbing the benefit of your effort and contribution right off. Some others need to experience firsthand before they get it (assuming they survive to make another choice). Some people can only see if you give it to them in the camera they can watch (like teaching a person to read with flash cards and getting nowhere, then upon further observance realize they are blind). And if your own vision or view or experience is limited despite appearing not so, then how will you come to know it, instead of placing the blame with others? Or as Chico Marx once said, "who you gonna believe, me or your lying eyes?"

Then there are the people who just have to go to the rally without a mask. The old saying about a horse ("you can lead a horticulture, but you can't make her think" or something like that) turns out to be quite sage there.

Finally, your experience is also subject to limitations in applicability, and may not be as universally true or generalizable as it appears to you that it should be. All those people who took thalidamide AS PRESCRIBED BY DOCTORS ALLOWED TO DO SO BY THE FDA, all those folks that used ranitidine instead of prilosec just when that adulterant got into a product run, they all trusted the same things you did.

Or maybe that's just nature, Darwin in action, or as Bill Cosby once related it: This guy shows up at St. Peter's Gate and the following conversation ensues: "How'd you die?" " Man, I drove a Volkswagen backward into the bay." "You go to Hell."

I say if you don't charge for your time, then you and your benificiary/customer can't complain about the results. Or as the USAF slogan about washouts goes, "Don't Aim So High."

My goodness but you do get a lot of replies.

I too have participated in many trials and I totally agree with your experience.

In particular I recommend taking a look at the work of Jay Nutt at OHSU.

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