In 2009 I attended a Stem Cell Awareness Day at The Parkinson’s Institute in Sunnyvale. All of the MDs were asked about stem cell treatment for Parkinson’s Disease, and why some people who go to China or Germany or where ever for stem cell therapy report improvements.
The MDs all pointed to the placebo effect. And they said that the bigger the intervention, the bigger the placebo effect. One example of this was a UCSF gene therapy trial from 2008 where the placebo group (who received no surgery but did get a hole drilled in their skull) had greater motor improvement in comparison to the treatment group (who got the gene therapy surgery).
Dr. Melanie Brandabur of The PI also noted that the placebo effect is not psychological alone. She said that the brains of Parkinson’s patients who receive these experimental treatments are somehow able to produce a bit more dopamine, demonstrating physiological changes.
A few people with multiple system atrophy have reported on the online MSA-related support groups that they’ve gone outside the US for stem cell therapy. Only one person has reported sustained good results. One gentleman recently reported that he concluded his wife experienced a placebo effect after her stem cell treatment in Germany.
Here’s an article about the placebo effect — a general look at the effect and then a specific look at how it occurs in Parkinson’s Disease drug trials.
Robin
http://www.apdaparkinson.org/data/NewsLetterUpload/APDAFal2005newest.pdf –> article on pages 10-11
Drugs Trials — The Placebo Effect
By J. Stephen Fink, MD, Ph.D.
American Parkinson Disease Associatio Newsletter
Fall 2005
A medication may have several effects on a patient. Some effects may be directly related to the medication’s effect on the body’s functions, which is called the pharmacological effect.
Another effect of a medication may not be linked directly to the medicine’s pharmacological effect. This is called the placebo effect. A placebo effect can be observed when a pharmacologically inactive substance is administered.
What is the placebo effect, what does the placebo effect have to do with the process of developing new treatments or new medications in controlled clinical trials, what is the importance of the placebo effect for clinical trials in Parkinson’s disease?
The word placebo comes from the Latin verb “placere,” that means, “to please.” Placebo is an inactive treatment and the placebo effect is the effect (usually beneficial) resulting from the administration of an inactive substance. When a patient receives any treatment (whether it is active or not) there may be a beneficial effect experienced by the patient just because there is an expectation of benefit. Placebo effects can result simply from contact with doctors or other health care providers, even in the mere act of interviewing or examining a patient. There may also be beneficial effects of additional treatment or improved care provided during the clinical trial of a new medication.
In addition to expectation of benefit, other contributors to this improvement in patients’ symptom scores may include the tendency for patients to enter trials when their symptoms are worse, and “bias” in the rater’s scoring of patients symptoms.
The beneficial effect resulting from the act of receiving treatment may be quite powerful and long lasting. For example, in some studies of asthma and pain, there was improvement of 30-40 per cent in subjects given placebo
(inactive) medications. The beneficial effect of receiving any treatment is not limited to medications, as the
expectation of benefit alone may lead to improvement in symptoms after surgical procedures as well.
The placebo effect can interfere with the assessment of whether a new medication or treatment is really beneficial.
Therefore, when new medications are tested, they are commonly compared to an inactive treatment (placebo); this is a placebo-controlled trial.
When neither the patient nor the examiner knows whether the patient is receiving active treatment or placebo, the
trial is referred to as “double-blind.” When the subjects are assigned to active treatment or placebo groups by chance, this is called a randomized trial. Randomized, double blind, placebo-controlled trials offer the most effective way to control for the placebo effect and have become the “gold-standard” in clinical trial design for assessing new drugs or treatments. For a new medication or therapy to be considered effective, it must be shown to be better than a placebo in a double-blind, randomized, placebo-controlled trial. Sometimes therapies that are thought to be effective are no better than placebo when tested in this type of trial.
Long lasting placebo effects have been reported in Parkinson’s disease. In some medication trials improvement in motor scores of 20-30 per cent in patients assigned to the placebo group has been observed for up to 6 months. Similarly, improvement and deterioration in Parkinson’s disease patients have been observed after the introduction and discontinuation, respectively, of placebo medication.
Placebo effects appear to be particularly evident in the clinical trials of surgical therapies. In the double blind, clinical trial of human fetal transplantation in Parkinson’s disease conducted by Fahn, Freed and colleagues, the control group received an “imitation” surgical procedure. Several of the patients in the control group rated themselves improved one year later. Similarly, 30 per cent improvement in motor scores in the placebo control (imitation surgery) patients was observed in the double-blind trial of porcine mesencephalic tissue. In this trial, improvement in the control group lasted at least 18 months, longer than had been previously observed in clinical trials of medications, suggesting that placebo effects may be stronger in clinical trials of surgical therapies.
What causes the placebo effect? It is not possible to test adequately for placebo effects in laboratory animal experiments because animals are not known to have responses to placebo. It has been assumed that the placebo
response is not mediated directly through a physical or chemical effect of treatment. However, a remarkable study by Jon Stoessl and colleagues demonstrated that the placebo effect in Parkinson’s patients was accompanied
by a release of brain dopamine from the remaining midbrain dopaminergic cells. This suggests that the improvement in motor function that is observed in the placebo groups of clinical trials in Parkinson’s patients might be due, in part, to actual physiological changes in the damaged brain dopamine nerve cells.
In summary, the placebo effect is important in the testing of new medications for Parkinson’s disease. It dictates
the design of clinical trials of new medications by the inclusion of placebo groups. The placebo effect might be considered to “benefit” those Parkinson’s disease patients who join clinical trials and are assigned to the placebo group, as they may demonstrate improvement in symptoms. Indeed, some of this improvement in symptoms in the placebo group may actually be due to beneficial changes in brain dopaminergic nerve cells.
This perspective underscores the often-spoken adage at Parkinson’s disease centers: “One of the best things to do when a patient first learns of the diagnosis of Parkinson’s disease is to join a clinical trial.” Among the many benefits of such participation may be the placebo effect!
Adapted from “The Placebo Effect in Clinical Trials” by Stephen Fink, MD, Ph.D. in the Summer 2005 Young Parkinson’s Newsletter.