BERLIN -- A phase III trial investigating whether a calcium channel blocker can slow progression of early Parkinson's disease recruited its full target population within a year -- 6 months ahead of schedule, researchers reported here.
Engaging all the stakeholders -- patients, patient advocacy groups, foundations, trial site managers, lead investigators -- was the driving factor behind getting 336 patients into the , , of Northwestern University, and colleagues at the .
"We believe the science behind the molecule really excited the investigators as well as the patient community," Simuni told 鶹ý. "I don't think there is one magic bullet. It was a combination of engaging the sites, hard work, and planning ahead."
The trial, funded by the National Institute of Neurological Disorders and Stroke (NINDS) and various Parkinson's disease foundations and pharmaceutical companies, is among the most closely watched in the disease, mainly because of the hypothesis that an old, generic drug for hypertension may modify the progression of Parkinson's.
In 2007, , Chair of the Department of Physiology at Northwestern University, and colleagues published suggesting that excitement of calcium channels in dopaminergic neurons played a role in the death of these cells, which is currently thought to be the main cause of Parkinson's disease.
If the "stress" of calcium channel activity on these cells could be reduced, perhaps that could have an impact on the disease, those researchers theorized.
Over the next few years, additional evidence from animal models and epidemiological studies led to phase II safety studies that similarly suggested that the calcium channel blocker isradipine held benefits for Parkinson's patients.
"Isradipine has been approved for high blood pressure since the 1990s, so we are all familiar with its safety and side effect profile, and it is generic and inexpensive," Simuni said.
She added that those phase II studies "to our pleasant surprise, did not show a significant signal of blood pressure reduction."
The NINDS took notice and funded the 36-month trial, which sought to enroll 336 patients with early Parkinson's disease within a year and a half.
But all the slots were filled -- with an additional 20 patients "on reserve" -- between Nov. 3, 2014 and Oct. 28, 2015. The final group also included a total of 34 minority patients.
In addition to engaging stakeholders, the researchers used recruitment tools such as a toll-free number to connect patients with a study site, a dedicated study website and email addresses, and printed brochures.
They also partnered with the Fox Trial Finder, which is run by the Michael J. Fox Foundation, as well as the NIH's recruitment offices.
Researchers not involved in the trial said the fast recruitment -- which is often a significant challenge for most clinical trials -- was impressive.
"It's amazing that they could put together this study, because they specifically needed de novo Parkinson's patients, and very early Parkinson's patients," commented , of the University of Gottingen in Germany, who was not involved with the study. "This old drug could be a potential disease-modifying strategy."
, of the University of Alabama at Birmingham, said the enrollment "reflects the strong interest in neuroprotective therapies in the Parkinson's patient community, together with a lack of other active trials of neuroprotection."
He noted that the mechanism in this study does not negate that of another hot area in Parkinson's research: drugs that target alpha-synuclein aggregation. Much like beta-amyloid in Alzheimer's, this protein has been found accumulating in the brains of patients with Parkinson's, and targeting it could hold promise for disease-modifying therapies.
Standaert said Surmeier "does not think the recent work [on alpha-synuclein] changes the importance of calcium channels; he sees them as modulating synuclein aggregation and explaining the selectivity of the disease."
Simuni agreed that the work should not have an impact on the development of alpha-synuclein therapies -- although she acknowledged that Alzheimer's researchers have been pursuing a similar path for many years, to no apparent benefit.
"We know it's not an easy path, but it's certainly the one that has to be pursued," she said.
The STEADY-PD III trial is expected to report its first results in the fall of 2018.
Disclosures
Simuni disclosed financial relationships with several drugmakers.
Primary Source
Movement Disorders Society
Greco BL, et al "Multi-modal recruitment strategy leads to expeditious enrollment in STEADY-PD III" MDS 2016; Abstract 2090.