The Largest Parkinson’s Disease Study Ever Attempted is Being Made Possible Only with Mobile Research Nurses

Situation

Because Parkinson's disease is a progressive brain disorder that leads to shaking and stiffness, eventually causing difficulty with walking, balance, and coordination, patients are at very high risk of fractures from multiple and sometimes severe falls that can lead to permanent disability and even death. Researchers are studying whether zoledronic acid, approved by the FDA to treat osteoporosis by increasing bone strength, will reduce fractures in people with Parkinson’s disease.

The Trial of Parkinson’s and Zoledronic acid (TOPAZ)¹ is seeking to enroll 3,500 participants over the age of 60, making it the largest double-blind, placebo-controlled, randomized clinical trial ever attempted in people with parkinsonism.

Anecdotally, only a very small proportion of people with parkinsonism receive treatment to reduce fracture risk. Barriers to seeking or receiving treatment include:

• a lack of evidence that medical treatments will reduce fracture risk in this population;
• the conventional approach to test for bone mineral density (BMD) and have follow-up medical visits to interpret, prescribe and assess response to treatment is unfamiliar to the neurologists who typically treat Parkinson’s patients; and
• the notably poor compliance with oral osteoporosis treatments may be even worse for older people with parkinsonism who are already burdened by taking several other medications.

TOPAZ was designed to overcome barriers to treatment by allowing people to enroll without the need for a doctor’s referral or BMD testing; treating participants with an intravenous infusion vs. an oral medication and, importantly, making the trial conveniently home-based.

The need to enroll such a large number of participants, many of whom have mobility and/or cognitive challenges, would make a traditional site-based study impossible. Even if the required number of prospective participants could be found living within a reasonable proximity to a clinical site, travel to and from the site would be very difficult if not impossible for many participants. It could also be time-consuming and expensive for the participant to get to the site and would put a burden not only on the patient, but also their caregivers.

The study recruitment began October 1, 2020 and is expected to be completed within three years.

Approach

Based on previous conversations with PCM Trials, researchers knew that a trial that would have been impossible to even imagine if it were site-based would actually be feasible using mobile research nurses. By involving PCM Trials in planning from the very beginning, they were able to design a study that could recruit a large number of participants from across a wide geography, and develop a multi-step protocol that could be done entirely from participants’ homes.

PCM Trials manages the study drug, including storage, blinding, randomization, and delivery to its Certified Mobile Research Nurses who have been trained on the study protocol. Participants receive a supply of vitamin D supplements and are instructed to take the medication for a period of time in advance of the nurse’s home visit to prevent the very low risk of hypocalcemia after the infusion. At the home visit, the participants are given one dose of the study drug intravenously. This treatment has been shown to prevent fractures in people with osteoporosis, with the preventive effects persisting for two years.

During the home visit, the nurse:

• obtains a “wet ink” informed consent signature (which supplements the online signature the participants would have provided when they enrolled)
• confirms that the patient has complied with the pre-infusion vitamin D regimen
• examines the mouth to ensure that there are no lesions that would predispose the patient to a rare side effect of the medication. If the oral exam is questionable, the nurse uses a secure smart phone protocol to send an image of the mouth to the study physician who immediately reviews it for eligibility
• takes a blood sample to obtain a rapid point-of-care measurement of renal function
• administers the I.V. study drug or placebo
• gives the patient acetaminophen to prevent a potential reaction to the infusion and instructs the patient on how to take the medication over the next couple of days to prevent side effects

In terms of communicating with the investigators, the PCM mobile research nurses:

• promptly communicate with the Coordinating Center through every step in the process as new patients are enrolled and home visits conducted
• refer patient questions to the TOPAZ help line
• track the process from the time of enrollment to the scheduling and completion of visits
• participate in TOPAZ Steering Committee calls every two weeks

Results

Because TOPAZ is a home-based trial, researchers are able to meet their goals of recruiting an unusually large number of participants from across the U.S., without the geographic constraints that would come with a site-based trial. Being able to recruit from a broad geographic area is enabling the study to include participants who are more representative of “real world” patients.And the fact that the study is patient-centric and convenient, which is especially important to a population of older patients with limited mobility, is also making it easier to recruit participants. The trial is ahead of its recruitment goals.

In addition, researchers at site-based trials sometimes conduct additional tests simply because the patient is at the clinic. Having a home-based study forces researchers to engage only in those activities that are necessary for the study. This, along with the fact that there is no overhead or staff costs of a clinical site, have resulted in an estimated cost savings of 80% per participant compared with a similar trial conducted in a clinical site.

This case study is based on a presentation delivered at OTC East² by Steven R. Cummings, MD, The San Francisco Coordinating Center. The San Francisco Coordinating Center is a non-profit academic research organization with more than 20 years of experience conducting multicenter studies and clinical trials. Watch the presentation, “Clinical Trials from Home, The Role of Research Nurses” here.

To learn more about how Decentralized Clinical Trial methods can help your trial, contact PCM Trials or submit an RFP today.

References

1. Tanner, Caroline M., et al. "The TOPAZ study: a home-based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism." NPJ Parkinson's disease 7.1 (2021): 1-6.
2. Cummings, Steven R. (2021, May 25-26). Clinical Trials from Home: The Role of Research Nurses [Conference presentation]. Outsourcing in Clinical Trials East Coast 2021, Virtual Event.