How Parkinson's changes over time in people whose movement symptoms persist despite medication

A Natural History Study of Treated Parkinson's Disease Patients Experiencing Motor Complications

This project will follow people with Parkinson's who still have movement symptoms despite medication to see how their symptoms and health records change over time.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 45 Years to 75 Years
• Sex: All
• Sponsor: Bayer (industry)
• Locations: 5 sites (Fountain Valley, California and 4 other locations)
• Trial ID: NCT07330258 on ClinicalTrials.gov

What this trial studies

This is an observational natural-history project enrolling people with clinically established Parkinson's disease who continue to have motor symptoms despite standard antiparkinsonian medications. Participants receive usual clinical care while researchers collect clinical measures such as MDS‑UPDRS motor scores, PD motor (Hauser) diaries, and electronic health/medical record data. No experimental treatments are given; data are analyzed to characterize symptom fluctuations, progression, and treatment patterns over time. The study focuses on patients 45–75 years old, within 4–<12 years of diagnosis and with measurable OFF-state motor disability and daily OFF time.

Who should consider this trial

Good fit: Adults aged 45–75 (with at least 30% aged ≤60) with clinically established Parkinson's disease diagnosed 4 to <12 years ago, modified Hoehn & Yahr stage II–III OFF, MDS‑UPDRS part III score ≥30 OFF, at least 1 hour/day OFF time, and on a stable levodopa regimen (≥300 mg/day or ≥3 doses/day) are the intended participants.

Not a fit: People with minimal motor symptoms, those younger than 45 or older than 75, those with very early or very advanced disease, or those not on the specified levodopa regimens would not match the study population and are unlikely to benefit from this project's findings.

Why it matters

Potential benefit: If successful, the findings could improve understanding of how motor symptoms progress on current treatments and guide design of better-targeted future therapies and trials.

How similar studies have performed: Similar observational natural-history efforts (for example PPMI and other PD cohorts) have successfully characterized progression and biomarkers, so this approach is established rather than wholly novel.

Eligibility criteria

Inclusion Criteria for Patient:

* Individual of any sex ≥45 to ≤75 years of age at informed consent (at least 30% ≤60 years of age).
* Diagnosis of clinically established Parkinson's disease (PD) as defined by the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for PD ≥4 and \<12 years from time of PD diagnosis at informed consent.
* Modified H\&Y stage II-III in the practically defined OFF-medication state (≥12 hours from last dose of antiparkinsonian medications).
* Score of ≥30 on MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III in the OFF-medication state.
* Presence of motor fluctuations with ≥1 hour of absolute time in the OFF state per day as assessed by clinician/patient at screening.
* Receiving stable antiparkinsonian medication regimen for ≥4 weeks prior to screening with a levodopa daily dose ≥300 mg or a dosing frequency of ≥3 times per day.
* Responsiveness to levodopa as determined by change in the following measures from the practically defined OFF state to ON state after taking typical first-daily dose of PD-medications: i. any degree of improvement (≥0.5 point) in modified H\&Y stage OR. ii. ≥30% improvement in MDS-UPDRS part III score.
* Montreal Cognitive Assessment (MoCA) score of ≥24.
* Agree to participate and provide signed informed consent.

Exclusion Criteria for Patient:

* Known history or presence of conditions that may provide an alternative to a PD diagnosis including but not limited to: multiple system atrophy, progressive supranuclear palsy, striatonigral degeneration, corticobasal syndrome/degeneration, vascular Parkinsonism, drug-induced Parkinsonism, essential tremor, diffuse Lewy body disease, Lewy body dementia, Huntington's disease, Wilson's disease, Fahr's disease, Alzheimer's disease, cerebrovascular disease, brain tumor, trauma, and infection.
* Known history or presence of significant vascular and/or cardiovascular disease limited to: stroke, transient ischemic attacks, poorly controlled hypertension, poorly controlled diabetes, unstable angina pectoris, or unstable myocardial infarction.
* Known history or presence of significant psychosis or impulse control disorder, or untreated or sub optimally treated depression.
* Known history or presence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, syphilis, or tuberculosis.
* Current or previously active malignant disease within the past 5 years, except definitively treated cutaneous squamous cell carcinoma, basal cell carcinoma, or in situ uterine cervical carcinoma.
* Currently pregnant, nursing, lactating, breastfeeding, or plan to be during study duration.
* Known history or current use of percutaneous levodopa/carbidopa intestinal gel, subcutaneous levodopa, or apomorphine pump.
* Prior history of brain surgery, including but not limited to: deep brain stimulation (DBS), pallidotomy, focused ultrasound thalamotomy, or other experimental neurosurgical procedure.
* Known history or current participation in cell or gene therapy procedures.
* Current participation in any interventional clinical trial.

Inclusion Criteria for Care Partner:

* ≥18 years of age at informed consent.
* Identified by the PD patient as their primary care partner.
* Agree to participate and the ability to provide signed informed consent independently, without the need for a legal representative.

Exclusion Criteria for Care Partner:

* Not applicable.

Where this trial is running

Fountain Valley, California and 4 other locations

• The Parkinson's & Movement Disorder Institute — Fountain Valley, California, United States (RECRUITING)
• Keck School of Medicine — Los Angeles, California, United States (RECRUITING)
• Boston University — Boston, Massachusetts, United States (NOT_YET_RECRUITING)
• University of Texas Health Science Center at Houston — Houston, Texas, United States (NOT_YET_RECRUITING)
• University of Vermont — Burlington, Vermont, United States (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Bayer Clinical Trials Contact

Conditions: Parkinson's Disease, Natural history study, Parkinson's disease, PD Motor Diary, MDS-UPDRS, Electronic health/medical records, Administrative claims data, Biological samples