carolyn, dottie, todd and Jean and all others who participate in clinical trials--Thank You for your courage. my husband has notqualified for any trials yet--would hae been considered for the coq10 trials, but was already taking a megadose. madelyn

Carolyn, it is great to have you back on-line with your firsthand insight (and much research) into this very important topic. I can't begin to tell you how brave I think you are to go where few have gone before and blaze a trail for all of us who one day may have to follow in your footsteps.

I'm not sure that I'm pioneer material, but that's a call none of us can make until we're in the moment. To be fair, we must recognize that each of us has very different personalities and tolerance of risk of any kind... and this is who we were before we were PWP. I know people who would never dream of crossing the street except in a crosswalk, and others who diligently plan every excursion so they will not have to make a left turn without a traffic light and an arrow. How could I ever expect them to understand why sham surgery might be an important part of clinical trials, much less why someeone would accept such risk.

Everything in life has pros and cons, and each of us must form our own conclusions and live with the natural consequences. I'm not a person of faith nor great scientific knowledge, just a pragmatist. If only the choices we have weren't so lousy.

Sheryl

...this is one of those occassions when I have reacted to a post on impulse rather than waiting to read all the facts and imbibe them before shooting my mouth off.Forgive me.
I too must extend my admiration to those courageous enough to offer themselves for this extensive form of "experiment." I am no coward,but have to say at present I can`t see myself as being brave enough to do such a thing.But then again I have no desire to hop into a rocket and jet out into the unknown.Neither do I enjoy the thought of creatures suffering in the name of science but then that would deem me a hypocrite of sorts.I am simply being honest with my thoughts.It just seems such a drastic procedure and Sheryl has hit the nail on the head with her parting phrase...shame our choices are so lousy.I agree.

My prayers are with all those who go through this.Truly.
Steff

Great Expectations: Why Do Placebos Affect People Differently?

19 Jul 2007
http://www.medicalnewstoday.com/articles/77244.php

Why do some people experience a "placebo effect" that makes them feel better when they receive a sham treatment they believe to be real while other people don't respond at all to the same thing, or even feel worse?

A new study from the University of Michigan Health System may help explain why.

Using two different types of brain scans, U-M researchers have found that the extent to which a person responds to a placebo treatment is closely linked to how active a certain area of their brain becomes when they're anticipating something beneficial.

Specifically, the research finds strong links between an individual's response to a placebo "painkiller", and the activity of the neurotransmitter known as dopamine in the area of the brain known as the nucleus accumbens. That's a small region at the center of the brain that's involved in our ability to experience pleasure and reward, and even to become addicted to the "high" caused by illicit drugs.

The new research, published in the July 19 issue of the journal Neuron, builds on research previously published by the same U-M team in 2005. That study was the first to show that just thinking a placebo "medicine" will relieve pain is enough to prompt the brain to release its own natural painkillers, called endorphins, and that this corresponds with a reduction in how much pain a person feels.

"Receptors for both endorphins and dopamine are clustered heavily in the nucleus accumbens. So, taken together, our studies delve directly into the mechanisms that underlie the placebo effect," says senior author and U-M neuroscientist, psychiatrist and brain-imaging specialist Jon-Kar Zubieta, M.D., Ph.D. "This is a phenomenon that has great importance for how new therapies are studied, because many patients respond just as well to placebo as they do to an active treatment. Our results also suggest that placebo response may be part of a larger brain-resiliency mechanism."

For the current study, Zubieta and his colleagues led by neuroscience graduate student David J. Scott combined information from two types of brain scan to come to their conclusions. They performed PET (positron emission tomography) scans on the brains of 14 healthy volunteers, and fMRI (functional magnetic resonance imaging) scans on those 14, and on 16 other healthy volunteers.

The PET scans focused on brain dopamine, looking at its activity as volunteers were told to expect, and then received, a painful injection of saline solution in their jaw muscle. They were then told to expect, and then received, an injection that they were told could either be a painkiller or a placebo. (Both were in fact placebos.) The fMRI scans looked at volunteers' brains while they played a game. Before each round, they learned that a correct answer would win or lose an amount of money, up to $5.

The PET scans were made using 11C-raclopride, which combines a drug that binds preferentially to dopamine receptors with a short-lived radioactive form of carbon that can be "seen" on PET scans. Throughout the PET scanning session, volunteers were asked to rate their level of pain on a numerical scale, and to describe any emotions they were experiencing.

Before the painful injection began, but after the volunteers had been told it was coming, they were also asked to guess how much pain relief they'd get from the "painkiller" if they received it. Half the volunteers were women, all in the same stage of their monthly cycle to avoid differences in hormonal state that might affect tolerance of pain - another topic that Zubieta's team has studied.

The PET scans and pain ratings revealed that as a group, the volunteers experienced significant pain relief from the placebo. But when researchers looked at each individual's results, they found that only half of the volunteers reported less pain when they received the "painkiller" placebo.

These placebo responders, as they were dubbed, had significantly more dopamine activity in their left nucleus accumbens than the other volunteers, beginning when they were told the painkiller medicine was about to begin flowing into their jaws. It also turned out that these individuals had also all anticipated the "painkiller" would give good pain relief before they even received it.

Meanwhile, of the seven individuals who didn't experience the placebo effect, four actually reported feeling more pain when the "painkiller" was delivered a phenomenon that has been dubbed the "nocebo" effect and has been observed in other situations.

Just to make sure that the volunteers' pain ratings weren't affected by the fact that they always received painful injections followed by placebo "painkiller", the researchers put a separate group of 18 male volunteers through the same experience twice, but no placebo was actually given, and actual PET scans were not done. Their pain and emotion ratings were significantly different from those of volunteers who received placebo.

"The results of these functional molecular imaging studies indicate that dopamine activity is activated in response to a placebo in a manner that's proportional to the amount of benefit that the individual anticipates," says Zubieta, who is the Phil F. Jenkins Professor of Depression in the U-M Medical School's Department of Psychiatry and a member of U-M's Molecular and Behavioral Neuroscience Institute, Depression Center and Department of Radiology.

The fMRI scans, which were performed on different days from the PET scans, revealed additional information about how individual expectations correlated with their placebo response. Each volunteer had an fMRI scan that looked at blood oxygenation throughout their brain, which allows researchers to spot areas where neurons (brain cells) are especially active as the individual performs a task or plays a game. In this case, the task was a very simple gambling game, in which subjects were scanned while expecting varying levels of a monetary reward or no reward.

As in the PET scans, the nucleus accumbens was a hotbed of activity as the volunteers were told how much money they could win or lose in the next round; as they waited for the round; and as they pressed the button and learned if they had succeeded in winning or avoiding losing money.

Then, the researchers compared the PET and fMRI scans for the volunteers who had had both types of scan. They also compared the ratings of anticipated placebo effect, the analgesia induced by the placebo during the pain studies, and the emotional changes associated with it. They found that those who expected a placebo to help them and got greater benefit from it (more analgesia, better emotional state) were also those who had the most activity in their nucleus accumbens during the anticipation of receiving a reward in the fMRI money game.

In addition to Zubieta and Scott, the study's authors are Christian Stohler, DMD, formerly of the U-M School of Dentistry and now dean of the University of Maryland School of Dentistry; Christine Egnatuk and Heng Wang of the U-M MBNI; and Robert Koeppe, Ph.D., director of the PET Physics Section in the Nuclear Medicine division of the U-M Department of Radiology. The study was funded by the National Institutes of Health.

University of Michigan Health System
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
United States
http://www.med.umich.edu

When I entered the hospital on June 26th for the Cere 120 clinical trial, I was casting my ballot for sham surgery. I never felt that a DBS was the way to go for me - don't know why. But, when I heard of the Ceregene procedure I was interested and ready to go. Did I have the therapy? I don't know and I won't know until the trial is complete.At that time if I had the sham I can elect to have the therapy along with the experiences - good or bad - of the oriiginal 17. I'd thought about it and decided I was ready to really listen to my MDS and just plain ready.In another post I believe I said I sick and tired of being sick and tired.

I see this surgery as another tool for the medical commuinity to use to find
something to give us relief .

Thank you for your kind words and best wishes.




Dottie



Dottie

Carolyn has included some very good reading material on sham surgery and the placebo effect. When I had my experimental surgery, we six KNEW we were getting the real thing. Yes, the placebo effect may have been in play here, but the 68+ volunteers for Phase II are part of the sham process.

I need to make it very clear that I am not trying to get sham surgery stopped - it has been studied scientifically and has been determined to be the only way to show if some t herapies are showing improvement signififcantly. However, the patient has a righth to kknow (via the informed consent process) AND I wonder if any stats have been gathered from all sham surgery trials to compare risks to benefits?

I and the group I volunteer with (Parkinson Pipeline Project) are just asking if this is really the best way to determine efficacy of new treatments.

Peggy

PS - be sure to answer the short survey at the Pipeline website: www.pdpipeline.org

Well I am an often reader, an occasional poster and a terrible typist. I'm also known to my closest friends as Spheramine 66. I have a few rambling thoughts on sham surgery. First as it relates to Spheramine, designated 'fast track status. Peg your surgery was 7 years ago. i must believe this was in development at least 5 years prior. Results will be released in fall 08 with antiicpated release on market in 2011. You say sham surgery is unknown. This drug will live 16 years minimum before release. Many of our friends will live in misery never knowing whats there. Without regard to benefits I feel the biggest concern in testing is sideaffects. Once that question is satisfactorily(sp) answered the big Q is 'Works or not?' I believe the big question in testing is more of Are the tests causing harm in any way. If it can be determined to be not threatening, then the potential benefits are a perk. i went into it thinking if I dont realize the planned results but it gets my name in a database for future opportunities it was a win. As far as sham goes, you gotta have it. 1 hour out of surgery, my dads shouting 'he got it it works. i havent heard him so clear in years'. Some days meds work so good I whisper thanks. Other days so bad I whisper THANKS. Our mind plays funny games. Without Placebo there is a major concern of readng test results. Ever read the answer to a puzzle and decide 'ok this I would have gotten right, but id have missed 4 of them, no on second thought 3. im not doing bad. Go to level 3.' I need more comfort in the results and placebo helps. Then any doctor with a stopwatch who thinks they can truly measure the speed, on or off, in which I stand with my arms folded across my chest is a bit off. Then try to pretend to drink air 3 times. With some of these tests I glad for placebo. So, Ramblesum, I favor placebo, disagree with test term for products showing no side affects.
My neurologist was dead set against me joining the stuy not wanting the study to receive the benefit and me nothing. When I decided he began to get excited but im not sure if it was for the potential benefit or because he would now be linked to a major study even if it was only in a warped 'seven degrees from kevin bacon' way
Some days i hope i got placebo, thinking it can only get better Other days I hope I didnt. It'll be over This put my family in much more torment then PD has me. Id love to offer more, maybe later, but this typing has got to end. Hi Peg

Very thoughtful post....thanks.

paula

Hey Carolyn -

I just learned today about your participation in this trial. I am so thankful for your bravery on behalf of all of us. I am not so brave. Not only would I not offer myself up for experimental brain surgery because of fear that I would be receiving the sham - my fear would also keep me away from the real thing! There is also a risk from the treatment itself. I am not willing to take that risk; I am grateful for those who do. I agree with Howard - this is the new frontier. All clinical trials participants are pioneers.

Sham surgery is a necessary risk for informed patients under our current system - it's those who actually receive the surgery plus treatment who are putting themselves at the most risk.

Is there really a movement now underway in the scientific community to abandon sham surgery in favor of another control protocol? Or is this question being asked to get information to improve the informed consent process?

I think any advocacy effort made to make sure the informed consent process is as thorough and secure as possible is time well spent. My thanks to those of you who are so involved.

Thanks Carey, hope the upper NW weather isn't too wet these days.

I am not alone in my "bravery." Dottie also is a participant in this trial. I did pay a small price for the doing though, but I am on the mend (see http://neurotalk.psychcentral.com/sh...ad.php?t=23386, then #4)

And, there is a movement about the Informed Consent happening. In retrospect...not hindsight...my informed consent has many holes in it which MUST be addressed for the successful future of clinical trials.

Hope to see you in October in NYC!!