In a recent webinar, Challenges of Drug Development in Early Parkinson’s Disease, Tom Babic, MD, PhD, our Vice President of Scientific Solutions in Neuroscience, uses his 40+ years of experience to share invaluable insights into the current state and future directions of early Parkinson’s disease (PD) research. Although clinical research in PD began more than 25 years ago, there have been no significant updates in the last decade. This gap highlights the critical need for disease-modifying treatments, particularly those that focus on the alleviation of non-motor symptoms, gait and disequilibrium signs, L-dopa fluctuations, patient quality of life, and caretaker burden.
Early PD: Symptoms & Diagnosis
While PD can be divided into four distinct states: prodromal, early-stage, mid-stage, and late-stage, Dr. Babic’s webinar focused primarily on prodromal and early-stage treatment. Prodromal PD starts significantly before typical motor presentation; in fact, 75% of dopamine neurons are often destroyed by the time a diagnosis is made.
While there are several risk factors associated with PD, including age, family history, environment, genetics, gender, and smoking history, there are also biological factors that serve as premotor markers, such as:
- Poor olfaction
- Constipation
- REM sleep disorder
- Autonomic problems
- Depression
Early motor signs often include bradykinesia, tremors, and rigidity. Using these indicators to diagnose early is key in PD treatment.
Challenges in PD Clinical Trial Design
One of the primary challenges in clinical trial design for PD is the imprecise understanding of the disease’s pathogenesis. There is no ideal animal model that accurately reflects the slow, progressive neurodegenerations seen in humans, which makes the development of an effective treatment for humans more complicated. Additionally, in clinical trials, the presence of effective symptomatic treatments can mask the effects of the investigational product (IP) effects, making it difficult to determine the true efficacy of the tested drug.
Other challenges PD clinical trials face include:
- Variable progression of clinical signs and symptoms
- Lack of available imaging measures to accurately assess all aspects of the complex neurodegenerative process
- The critical need to demonstrate a long-term safety profile of an IP
- The need for combination therapies rather than the use of a single drug
Early PD Treatment Approaches
One of the most well-established treatment approaches to PD is where patients are prescribed Levodopa or dopaminergic agnostics at the start of their symptomatic period. As a result, patients often experience a honeymoon period, where the majority of patients have an excellent response to treatment, typically lasting one to three years. However, this effect eventually subsides, known as the wearing-off phenomenon, and the patient faces complications or more doses are prescribed.
Currently, the concept of the golden year is becoming increasingly popular in early PD, a phrase coined by Dr. Robert Hauser a few years ago. This concept encompasses a symptomatic treatment-free period, allowing patients to participate in clinical trials without the confounding effects of existing treatments. Dr. Babic discusses the ethical considerations of delaying symptomatic treatment, noting that the majority of investigators – two-thirds – find a delay of about 5-6 months acceptable. However, the decision to postpone or move forward with treatment is often driven by the patient’s wishes rather than objective findings.
Recruitment Challenges & The Role of the Investigator
Patient willingness to participate in clinical trials is a significant challenge in early PD research, and investigators can play a considerable role in explaining the trials to patients to help mitigate this barrier. The complexity of study protocols can also impact recruitment rates, with site personnel being the main source of patients for clinical trials, followed by neurologists and trial finders. Dr. Babic emphasizes the importance of establishing a strong infrastructure to optimize study success, including:
- Research team
- Recruitment plan
- Recruitment activities record
- Communication with patients
- Networks of physicians & associations
- Prescreening record
- Trial finders
- Recruitment toolkit
It’s additionally essential to identify optimal characteristics in the investigators, such as their preference for the honeymoon or golden year approach, their experience in randomized controlled trials, and their motivations.
Watch Dr. Babic’s On-Demand Webinar
To gain a deeper understanding of the challenges associated with early PD clinical research, watch the full on-demand webinar today. From endpoint selection to the use of biomarkers, Dr. Babic’s comprehensive presentation goes in-depth about various critical factors regarding PD drug development.
At Worldwide Clinical Trials, we’re committed to advancing research in PD with support from leading experts like Dr. Babic. Contact us today to learn more.
