MJFF has funded atleast two researchers to study PD subtypes and disease progression. The subtypes defined in these studies are different from whats been discussed here. One of the abstracts is as follows: I hope some of the data from these studies can be reanalyzed for the features discussed here without having to do a new study. Any thoughts on how to do that?


Taken from MJFF Website http://www.michaeljfox.org/research_...s_3.cfm?ID=298
Defining PD Subtypes Based on Patterns of Long-term Outcome

PD Subtypes 2007

The purpose of our study is to identify Parkinson’s disease subtypes based on how individuals are doing approximately seven to eight years after diagnosis. Some patients have few symptoms at this time, while others may have problems with thinking and memory, balance, mood, motor fluctuations and dyskinesia, parkinsonism (slowness, stiffness, tremor), or autonomic function (blood pressure, urinary, and bowel function). We will analyze two long-term studies (DATATOP - Deprenyl and Tocopherol Antioxidant Therapy of Parkinsonism and CALM-PD - Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinson’s Disease) and attempt to identify groups of patients with similar patterns of symptoms. We will then analyze characteristics of these patients when they were first diagnosed and treated to determine if we are able to predict their pattern of symptoms seven to eight years after diagnosis.

Early identification of patients who are anticipated to develop particular patterns of symptoms may allow selection of specific therapies that will improve long-term outcome and specific subtypes of patients may be selected for entry into clinical trials designed to evaluate therapies to forestall the development of that pattern of symptoms. In addition, identification of distinct PD subtypes may aid in delineating genetic and environmental causes of PD.

Researchers

Robert A. Hauser MD, MBA
University of South Florida
Parkinson’s Disease and Movement Disorders Center

Michael P. McDermott, PhD
University of Rochester
University of Rochester

From MJFF web site under research
http://www.michaeljfox.org/research_...s_3.cfm?ID=298
Phenoprofiling PD

PD Subtypes 2007

Parkinson's disease is generally characterized as a movement disorder. Over the last years, however, there has been an increasing awareness that many people with PD may also suffer so-called "non-motor features," including problems with mental functioning, depression, falling asleep or staying awake, and autonomic functions (for example bladder and bowel problems). Furthermore, when patients are treated over the long term with dopaminergic drugs (e.g. levodopa) they may start to experience motor or psychiatric side effects. Although all these different features are aspects of PD, not all PD patients will have the same problems. There are differences between patients concerning the age at onset of their symptoms, the rate of disease progression, and the combination of symptoms and side-effects, suggesting the existence of subgroups. These clinical differences between patients may in turn result in different consequences on the level of disability, quality of life and required care.



Fundamental to our understanding of how one patient may differ from another is the availability of good quality measures that cover the broad spectrum of motor and nonmotor features of PD. The SCales for Outcomes in PD (SCOPA) program (www.scopa-propark.eu) was begun in 1999 to develop rating scales that measure motor and nonmotor features of PD as well as disability and global outcomes of health. In 2003, the SCOPA-PROPARK cohort study started, in which 420 patients are evaluated annually with the SCOPA scales.



The current project aims to identify groups of patients (subtypes) that share characteristics with respect to their motor and nonmotor features and their progression. Knowledge about how the expression of PD varies between patients may help our understanding of the mechanisms that underlie the development of the disease.

Researchers

Jacobus Johannes van Hilten MD, PhD
Leiden University Medical Center
Print This Page Email This Page

*

girja (and Stitcher who gave a snip of these studies earlier) - thanks for this info. It appears (and I am not surprised) that the Fox Foundation has been on top of this subtype thing. This information has probably passed by me several times (a good reason to have flashing lights and bells and whistles attached to such studies - lol).

Such studies, however, would require the input of several people with PD who are knowledgeable enough about the disease to differentiate between categorizing symptoms common to PD and those not. And as paula has said before, NeuroTalk would be a good vehiclel for providing such information.

So, what are we waiting for?
Peg

PS - meant to add that Doctors Hauser and van Hilten (Netherlands) are excellent choices for these studies.

Thank you MJFF and Dr. Ray Bartus, for hearing our pleas to understand these trial failures before reading about them two years later in a potentially biased journal.

Regarding Cere 120, this interview tackles the hard questions, it sounds honest, and now potential phase III participants [should it occur] can go in with their eyes wide open. I think you'll be able to recruit advanced patients. Just as becoming elderly involves facing certain facts [which is sometimes labeled as negativity, but it isn't, IMHO]about a dwindling future, pwp cannot deny that they are facing some serious poor health and suffering in the near future. Expectations for a cure in our lifetime are not necessarily there. This could result in more wanting to help others down the line, and to take the risks in clinical trials when quality of life is deteriorating.

Also, no matter how many studies are published about DBS, there are many many pwp who do not believe they are worth the risk.

So I can't thank you enough for the article; its publication is consistent with your efforts to move at a quick pace. To me, tho, it reflects respect for patients and hopefully will result in increased trust, support and communication between the research and patient communities.

http://www.michaeljfox.org/research_...icle.cfm?ID=11

my wishes for success,
paula

This issue must be addressed. I think we can do it, I sent almost all of this out to some groups already by email, not to agitate [I would just admit it if I was] but to...oh fill in the blank. There are many reasons - it's one of the main things. People with emotions are the reason we are all unpredictable - our mind/body connection separates us from animals [ at least in some pretty important ways] and money.

Sent last night:

After writing and being published with questions about trial protocols and sham surgery emphasized as being questionably ethical for the last several years, it seems that we are in the middle of what you could call an application phase. MJFF did the Bartus interview, which answered many of our questions, tackled the hard issues, and risked future business or interest in cere 120. It sounded honest, but now also seems like the most opportune moment to pull out the Declaration [formerly Bill of Rights] and see how their performance compares to our expectations, particularly regarding the sham surgery participants getting the treatment. Hopefully, both sides are listening.

This was a first that I know of- this interview - and I think it was a result of a lot of squawking on our part, along with a lot of hard work from all stakeholders - everyone. MJFF came thru with the info, and did it immediately..after funding it quickly. We were watchdogging right there all along as well. So let's take a look. Where is the latest copy of the Declaration and checklists? Is it all on the pipeline site?

Here's some information that could help. The full interview, a must read, is here: it is outstanding - the pd community has come a long way since GDNF.

http://www.michaeljfox.org/research_viewpoints_newsInContext_article.cfm?ID=1 1

Below are some very important comments.

Ray Bartus comment regarding those who received sham surgery about 'what's next'?

MJFF: If you launch a second CERE-120 trial, will you be able to re-enroll the trial participants who received sham treatment in the first study?

RB: I actually raised that issue and discussed it with my colleagues. Wouldn’t that be a great thing to do? You have these patients who were courageous enough to volunteer for this study, but they got sham treatment, so wouldn’t they, therefore, be great candidates? From a humanistic standpoint it would be a great thing to do. But from a scientific standpoint, you quickly realize that you would really compromise the program by going in that direction.

First of all, the patients have now progressed another year or two from where they started with our trial. There is a very general consensus, based on some data and a lot of intuition, that the more the disease progresses, the less benefit one might expect from CERE-120. Thus, using these patients for an important ‘go/no-go’ decision could represent a serious mistake if the dosing change indeed worked but we did not see a strong effect because of their disease progression.

Secondly, 70 percent of those patients have already showed a robust response — that is, a placebo response. If they already have an elevated baseline, we could be shooting ourselves in the foot trying to overcome that. You see how complicated it gets.

From two sham surgery participants:
Dottie
From Informed Consent:

If it is determined at the conclusion of this study that it is appropriate to provide CERE-120 to people with Parkinson's disease, those assigned to the sham surgery group may be permitted to enroll into an open-label follow-up study in which CERE-120 will be given"

The Questionnaire has this:

After the study is completed, you will be informed about which group (active treatment with Cere- 120 or sham surgery) you were assigned. If you were assigned to the sham surgery group, are you aware that you will have the option to receive active treatment with CERE-120? Yes/No

I [Dottie] sent the coordinator the following:
" Someone asked me about the option of having the surgery - did that end with the completion of phase 2 or does it carry over to phase ?

Her [coordtinator] reply:
"...I have not heard anything regarding a possible phase 3. I was told the last time I inquired that they were still in discussions as to what and if there would be a next step even with the sham group".

This is not complete or conclusive information. Dottie is still checking.

Tom819
From the consent form:

"If results confirm the continued safety and efficacy of CERE-120 following the conclusion of the trial, another study will be opened to allow subjects who received the sham surgery to receive the study drug CERE-120. Participation will be made available to all subjects deemed suitable for the surgical procedure by the subjects study neurologist and neurosurgeon."9

Perhaps none of the sham surgery participants will want the treatment now. But the question does need to be addressed if a Declaration is ever going to have meaning don't you think?

I think the interview is awesome and historic as clinical trials go, can we carry it through? The placebo and mind trickery really are a problem all around. I appreciate that everyone is trying to solve it and the speed at which it has been moving is as refreshing as a windy day in Florida.

Declaration of Rights and Resp. written by pd Pipeline Project and other pwp, along with PDF

Copy of corresponding expectations are largely in this section.

1. Clinical trial participants with Parkinson's disease have the right to post-study information and options for care including:

• Trial results.
• Information about the conditions which they may receive post-trial access to the experimental treatment.
• Notification as to whether they received a placebo or the experimental treatment and at what dosage.
• The option for participants in the experimental/treatment group to continue the treatment. Likewise, those who received placebo or low dose treatments, or sham surgery should have the option of receiving the experimental treatment at the full dose, upon conclusion of their trial.
• Results of all tests and procedures and copies of scans, x-rays, MRI’s, etc. if requested by the participant.
• Updates about all adverse events following trial conclusion.

http://www.pdpipeline.org/advocacy/rights.htm

paula

.

Both Dr. Bartus and the Fox Foundation should be applauded for their willingness to honestly and publicly discuss the CERE-120 trial results. It was also encouraging to hear that Ceregene is not abandoning the research, as so many other companies have done when their primary endpoints were not met. Instead Dr. Bartus stated that Ceregene is considering a new trial (phase 2 or 3?), Based on what they learned from the current trial, they would use a higher dose and target the nigra (nigral cell bodies ) as well as the putamen. These changes would require FDA approval.

Bravo Ceregene!

And I wish I could end this message right here. But there is another issue that begs for more discussion -- the availability of CERE 120 treatment for the Phase II sham surgery group, if any of these trial participants do wish to receive it.

From the Interview:

“MJFF: If you launch a second CERE-120 trial, will you be able to re-enroll the trial participants who received sham treatment in the first study?

“RB: I actually raised that issue and discussed it with my colleagues. Wouldn’t that be a great thing to do? You have these patients who were courageous enough to volunteer for this study, but they got sham treatment, so wouldn’t they therefore be great candidates? From a humanistic standpoint it would be a great thing to do. But from a scientific standpoint, you quickly realize that you would really compromise the program by going in that direction.
First of all, the patients have now progressed another year or two from where they started with our trial. There is a very general consensus, based on some data and a lot of intuition, that the more the disease progresses, the less benefit one might expect from CERE-120. Thus, using these patients for an important ‘go/no-go’ decision could represent a serious mistake if the dosing change indeed worked but we did not see a strong effect because of their disease progression.

Secondly, 70 percent of those patients have already showed a robust response — that is, a placebo response. If they already have an elevated baseline, we could be shooting ourselves in the foot trying to overcome that. You see how complicated it gets” (end of interview statement)

Yes, and this is where PWP and researchers may have differing outlooks.
“First of all, the patients have now progressed another year or two from where they started with our trial.” -- To me, isn’t that is exactly why the sham surgery participants should be offered treatment. They are getting worse day- by- day, and there is nothing else presently available for clinical use proven to stop the progression, as CERE120 is thought to do. They volunteered to participate in the Ceregene trial, both to help advance the research and also with hopes of improving their conditions. They entered the trial with the understanding that if CERE 120 was shown to be safe and effective, they could receive the treatment (see the two Informed Consent provisions posted by Paula on this thread on 1/31 “A Plan About Expectations”) Perhaps that was why they agreed to the possibility that they might receive sham surgery.
Additionally, from the Minutes of the NIH Recombinant DNA Advisory Committee meeting in 09/06 , that reviewed and approved the CERE120 phase II protocol at:
http://oba.od.nih.gov/oba/rac/minute...utes_09-06.pdf
RAC discussion: p.6
"Towards providing some potential for eventual benefit, if upon completion of the blinded portion of the trial CERE-120 is determined to be safe and effective, the sham subjects will gain access to CERE-120 in an open-label extension study.
p. 7-8
“Since participants have received a gene vector that may allow the protein to be expressed for the individual’s lifetime, the investigators will continue following these individuals over the long term. Dr. Bartus explained that the investigators are in the final stages of putting together a long-term followup protocol for all participants that would assess them every 6 months indefinitely. The investigators also intend to offer participants recruited into the proposed sham treatment group the opportunity for treatment following the break of the blind, and then they also would be followed long term following that treatment. “

p.9
Synopsis of RAC Discussion and RAC Observations and Recommendations
“Expand the discussion of the risk-benefit ratio for participants receiving sham surgery. Additional information also should be provided about the criteria that will be used to determine which participants in the control group will be eligible to receive CERE-120 at the end of the study. “

Dr. Bartus stated in the interview that there were no safety problems. Although the end points were not met, Ceregene thinks they know what went wrong (dose and target areas) and how to fix it in a future trial. If treatment can be given to a new phase II or III participants, why not to this sham surgery group in an open label extension trial? They could then also be part of the long-term followup studies. There are examples of other sponsors running concurrent placebo control and open label studies (for those who have completed the controlled study). Of course, maybe there are other factors we are not aware of.

Yes Paula, I think the Declaration of Rights provisions about post-study options were written to address situations like this one.
“Clinical trial participants with Parkinson's disease have the right to post-study information and options for care including:
• Trial results.
• Information about the conditions which they may receive post-trial access to the experimental treatment.
• Notification as to whether they received a placebo or the experimental treatment and at what dosage.
• The option for participants in the experimental/treatment group to continue the treatment. Likewise, those who received placebo or low dose treatments, or sham surgery should have the option of receiving the experimental treatment at the full dose, upon conclusion of their trial.
• Results of all tests and procedures and copies of scans, x-rays, MRI’s, etc. if requested by the participant.
• Updates about all adverse events following trial conclusion. “
http://www.pdpipeline.org/advocacy/rights.htm
Ceregene has been an admirable clinical trial sponsor, especially in moving the research along and trying to be responsive to patients. Hoping they will be willing to look into this issue as well.

Just inserting here the fact that this issue is owned by everyone. Even tho not everyone wants to spend time on this particular aspect, everyone is invited to this discussion.

It's focused and moving. It's provocative but respectful. It's spontaneous but professional. I haven't called anyone a yellow bellied chicken liver for yet another week, taking into consideration that humor is only to be expressed ....somewhere else.

Thoughts don't count -

paula

I usually don't say anything in these threads, I'm not sure why. I haven't read this one until this morning, and I know why. It's too real, it's too scary, it's too upsetting, I have spent enough energy staying tuned in my own little world recently. My doctors are very helpful in keeping me boosted, but there are so many things we don't understand, and to be told that I can't understand makes me angry, affecting my balance, mental and physical.

To we who live this thing, know this: every time a medical person asks me to what I attribute my slow progress and relatively good function, I list several fact-based reasons, including the fact that a lot of people are praying for me.

I have had periods of time when I decide to get better, and I do.

Beyond my self, stranger things happen. A friend who is a pianist burned her fingers over a steamy pot. As she soaked the fingers in ice water, I laid my hands on her burned one, and as a Reiki practitioner allowed some of the life force to flow through me to her injury. Some of the pain went away. What happened? I have no idea. It just works. (For Peg and Paula, I consider the Reiki force to be the holy spirit's work and the act of laying on hands to be a form of prayer.)

I am not asking for a study of religion (although that could be intriguing), but a study of attitude, as others above have suggested. For that, clients/patients/consumers/customers should surely be in a focus group with input to the researchers and their IRB, if not at the conference table.

Jaye

PDF - Clinical Research Learning Institute

[Now is the time to speak up and become part of this "focus group."]

The Clinical Research Learning Institute is an annual multi-day educational seminar for people with Parkinson’s. It provides the knowledge and skills for each participant to be an effective representative within the clinical research enterprise.

The Learning Institute aims to create a place at the table for people with Parkinson’s disease (PD) to share their viewpoints and experience – which is all too critical to moving the development of treatments for PD forward — yet it is all too often overlooked.

The 2008 Institute took place on Thursday, July 10 through Saturday, July 12 in Glen Cove, NY. It included 27 people with Parkinson's from across the country and Puerto Rico in its inaugural year. [Plans for 2009 are not yet announced.]

Learn more about the Learning Institute:

So PDF.org is looking for people to attend the 2009 institute?

That's terrific!!