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Participation of Early Parkinson’s Patients in Clinical Trials Crucial to Finding Cure, Expert Says

The time between diagnosis and implementation of symptomatic treatment is critical in the effort to find a cure for Parkinson’s disease. However, many early Parkinson’s patients wait too long before seeking medical attention, leaving researchers with a small group of candidates for clinical trials, says Robert A. Hauser, MD, the director of the Parkinson’s & Movement Disorder Center at the University of South Florida.

In his commentary, “Help cure Parkinson’s disease: please don’t waste the Golden Year,” published in the journal npj Parkinson’s disease, Hauser stresses the importance of early Parkinson’s patients participating in clinical trials before they start taking symptomatic medications.

The discovery that Parkinson’s is associated with aggregation of misfolded alpha-synuclein proteins in the central nervous system suggests there are many potential targets for therapeutic intervention.
Researchers are enthusiastic about the idea that the disruption of this process, or removing toxic aggregates, can slow or stop disease progression. Unfortunately, there are still no validated biomarkers, such as a simple blood test, that can help monitor disease progression or test promising therapies in Parkinson’s patients.

So far, the most common way to test a therapeutic candidate is to assess its capacity to slow the progression of clinical signs and symptoms compared with placebo over time in patients with early Parkinson’s who are not yet receiving symptomatic Parkinson’s medications — such as levodopa, dopamine agonists, and MAO-B inhibitors.

However, this can prove to be a challenge, since patients with early Parkinson’s disease can only be followed, without the use of symptomatic medication, for about six to 12 months, what Hauser calls the “Golden Year.” After this, many patients will need medication to relieve symptoms.

“The critical time of about one year from when the patient can be diagnosed with early PD [Parkinson’s disease] based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year,” Hauser said in a press release. “It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease.”

Interference from symptomatic medications makes it difficult for researchers to tell if the potential treatment being tested is slowing disease progression or if they are just seeing effects from those other therapies.
However, patients with early Parkinson’s who are available to enroll in a clinical trial and whose symptoms are mild enough are in short supply.

Therefore, to test promising potential disease-modifying therapies, patients with early Parkinson’s have to be identified and referred to clinical trials before they go on symptomatic medications. Unfortunately, this is often not the case.
“If the time period over which we test the intervention is short, we reduce our ability to identify a difference between the intervention and placebo. If the time period over which we attempt to test the medication is too long, a substantial proportion of patients may require institution of symptomatic therapy and we lose our ability to monitor clinical disease progression during the observation period,” Hauser wrote.

Source: Parkinson’s News Today

Record Pace of Recruitment Speeds Isradipine Trial

Great Clinical Trial Insight from the Michael J Fox Foundation By Allyse Falce.

Clinical trial news update: A recent MedPage Today article, “Quick Enrollment for STEADY-PD III Trial,” highlighted the accelerated enrollment of participants in the Safety, Tolerability and Efficacy Assessment of Dynacirc for PD (STEADY-PD) III trial, thanks in part to MJFF’s online trial matching tool, Fox Trial Finder.

A few months ago, we interviewed Kevin Biglan, MD, MPH, associate chair of clinical research for the Department of Neurology at the University of Rochester and co-principal investigator of STEADY-PD. Read more below about the trial and the remarkable efforts that led to the study’s successful recruitment:


Phase III testing for the compound isradipine is progressing after a remarkably short recruitment period; 336 participants enrolled in less than one year. Slow recruitment is a significant roadblock to testing of potential treatments and slows the pace of bringing new drugs to market. This success advances the pace of this study and may serve as a model for other programs.

Isradipine is a calcium channel blocker currently prescribed to treat high blood pressure. It came to the attention of Parkinson’s researchers when data from large studies showed lower risk of Parkinson’s disease (PD) among people who took the drug for hypertension. Scientists believe isradipine works to prevent the death of dopamine-producing cells and therefore may slow the progression of PD. The Michael J. Fox Foundation (MJFF) funded pre-clinical work to make that connection, as well as the Phase II trial. In 2014, isradipine researchers received a $23 million grant from the National Institutes of Health to move the Safety, Tolerability and Efficacy Assessment of Dynacirc® for PD (STEADY-PD) study into Phase III efficacy testing. Dynacirc® is the commercial name of the isradipine hypertension drug.

Kevin Biglan, MD, MPH, associate chair of clinical research for the Department of Neurology at the University of Rochester, is co-principal investigator of STEADY-PD. Dr. Biglan spoke to MJFF about the study’s successful recruitment period, and answered some commonly asked questions about Parkinson’s disease and calcium.

MJFF: Congratulations on completing study recruitment. What kind of participants were you looking for and how did you find them?

KB: We were looking for newly diagnosed individuals who had not yet started treatment for PD. Traditionally, this is a very difficult population to recruit. These individuals are just getting the news that they have Parkinson’s disease, and they’re not necessarily thinking about participating in research. And a lot of newly diagnosed people need treatment right away, so that eliminates many potential volunteers.

About 60 percent of people enrolled directly through the 55 study sites. The second largest group came through the MJFF online trial matching tool Fox Trial Finder. One hundred people were prescreened through the site, and about half of them ended up enrolling. And another subset of participants were referred by neurologists outside of the study sites.

Our timeline was 18 months; we were six months ahead of schedule. We worked with MJFF on a recruitment plan, and we think our methods of communication with the study sites and with volunteers who came through other sources may be of use to the Parkinson’s research community. We’re planning to write an article and share those tactics soon.

MJFF: How does accelerated trial recruitment speed drug development?

KB: The biggest barrier to drug development is enrolling an adequate number of individuals into a study. A lot of the time and costs of trials are associated with this delay in recruitment. The longer it takes to get people into a study, the longer it takes for us to find the results.

MJFF: When might isradipine be approved to treat PD?

KB: The last person will be out of the study in November 2018. After that, it’ll probably be about three to six months before we have final results. That would put us into the beginning of 2019. If the results look promising, because it’s a readily available drug, it may be prescribed for Parkinson’s soon after.

MJFF: Many Parkinson’s patients who don’t have hypertension have asked if they should begin taking isradipine. Is this a good idea?

KB: At this point, we still don’t know that isradipine has beneficial effects on Parkinson’s disease, so we recommend that people don’t start taking this medication until we have more information. Also, low blood pressure is a symptom of PD, and if you don’t have hypertension, this medication may exacerbate that condition. There are other side effects, mainly dizziness and swelling, associated with isradipine, too. Certainly, before you start any medication you should talk to your physician about it. There could be something specific to you that might put you at higher risk of developing problems, so it’s not something people should start without some discussion.

MJFF: If a patient is currently taking another calcium channel blocker, should they switch to isradipine?

KB: If a person with PD needs to be on a calcium channel blocker, for whatever reason, high blood pressure or otherwise, and their cardiologist or primary care doctor thinks isradipine is a reasonable alternative choice, then there’s likely no harm in switching between calcium channel blockers. But again, that’s a discussion that needs to occur between the patient and physician.

MJFF: Since this is a calcium blocker, should people stop taking calcium supplements? Or cut out calcium-rich foods?

KB: There’s no reason to worry about calcium supplements or calcium-rich foods. With isradipine, it’s targeting a specific calcium channel in the brain that we think may play a role in the cause of Parkinson’s disease. Calcium itself is highly regulated in the bloodstream. You don’t need to stop taking calcium supplements or avoid calcium-rich foods; there’s no evidence that those things have any negative effect on Parkinson’s disease.

MJFF: Thanks for speaking with us, Dr. Biglan. Anything else you’d like to add?

KB: We’re incredibly grateful to the Parkinson’s community for their partnership in this study. It’s going to allow us to answer a very important question about whether this treatment can slow progression of Parkinson’s disease sooner than we would have been able to without the assistance of patients, their families, and advocacy and research organizations.

Source:: Fox Feed Blog