Clinical trial NCT06790381: Effect of Biological Sex on Multimodal Biomarkers of Disease Progression in Patients with Parkinson's Disease
Official title: Effect of Biological Sex on Multimodal Biomarkers of Disease Progression in Patients with Parkinson's Disease: from Pathophysiological Mechanisms to Equitable Health Outcomes
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Parkinson Disease
Keywords: sex Hormones
Neuroimaging
Biomarkers
Parkinson&amp;#39;s Sex differences
Parkinson&amp;#39;s progression
non-motor symptoms
motor symptoms
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Università della Campania Luigi Vanvitelli
name: University of Catanzaro
First posted: 2025-01-24
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Parkinson's Disease and healthy controls

Brief summary: The GENDERIZE-PD study is a research project to understand how biological sex affects the progression of Parkinson's disease (PD). PD is a brain disorder that causes both movement and non-movement symptoms. Researchers aim to identify differences between men and women in how the disease progresses and in the biomarkers (biological indicators) related to the condition.

Study Goals:

Identify differences by sex in how PD develops and progresses, using clinical assessments, brain scans, and blood tests.

Find predictors of disease progression that may help create personalized treatments for men and women.

Study Details:

Type of Study: Observational, with additional procedures (e.g., blood tests and brain scans).

Participants:

120 people with early-stage PD (60 men, 60 women) diagnosed within the last 3 years.

90 healthy participants (caregivers or relatives) for comparison.

Procedures:

Clinical exams and questionnaires about movement and non-movement symptoms (like sleep, mood, and fatigue).

Blood tests to measure hormone levels. Brain imaging to study changes in structure and activity. Timeline: Participants will be followed for 18 months, with evaluations at 0, 6, 12, and 18 months.

Why This Study is Important:

Men and women often experience PD differently. For example:

Men are more likely to have memory and thinking problems. Women may develop movement side effects from treatments more often.

Understanding these differences can lead to:

Improved care plans tailored to men and women. Better treatment outcomes by focusing on sex-specific factors.

Who Can Join:

Adults aged 18-80 with early-stage PD or healthy individuals willing to provide blood samples and undergo brain imaging.

Exclusions include women not in menopause and people with certain medical or other health conditions.

Study Locations:

The study is conducted at three centers in Italy:

San Raffaele Scientific Institute - Milan (led by Prof. Federica Agosta). University of Campania "Luigi Vanvitelli" - Naples (led by Prof. Alessandro Tessitore).

University "Magna Graecia" - Catanzaro (led by Prof. Gennarina Arabia).

Detailed description: Overview:

The GENDERIZE-PD study investigates how biological sex influences the progression of Parkinson's disease (PD). This groundbreaking project seeks to uncover sex-specific differences in clinical symptoms, disease progression, and biomarkers to enable more personalized and equitable treatment strategies for men and women. By examining a range of biological, clinical, and imaging data, the study aims to provide a deeper understanding of the disease and identify predictors of progression.

Background and Rationale:

PD is a progressive neurodegenerative disorder characterized by motor symptoms (e.g., tremors, rigidity) and non-motor symptoms (e.g., mood disturbances, sleep problems). The disease affects men nearly twice as often as women, and differences between the sexes have been observed in clinical presentations and treatment responses:

* Men with PD are more likely to experience cognitive decline.
* Women with PD are at higher risk of treatment-related motor complications.

Emerging evidence suggests that biological sex impacts brain structure and function, potentially influencing the course of neurodegenerative diseases like PD. Hormonal factors, such as testosterone and estrogen, play key roles in brain health and disease susceptibility. This study seeks to clarify these sex-based differences by analyzing clinical, biological, and neuroimaging data.

Objectives:

The study is designed to achieve the following:

1. Primary Objective: Identify clinical differences between men and women with early-stage PD, focusing on motor and non-motor symptoms, and correlate these findings with sex hormone levels.
2. Secondary Objectives: Investigate sex-specific differences in brain imaging results, including MRI and dopamine transporter (DAT) scans, and biomarker profiles.
3. Exploratory Objectives: Evaluate the predictive value of biomarkers for disease progression and explore sex-independent patterns of PD progression.

Study Design:

This is a multicenter, observational, prospective, case-control study with a longitudinal follow-up of 18 months. The research involves three Italian centers:

1. San Raffaele Scientific Institute - Milan
2. University of Campania "Luigi Vanvitelli" - Naples
3. University "Magna Graecia" - Catanzaro

Study Phases:

1. Baseline Cross-Sectional Analysis: Collect clinical, imaging, and biological data to establish sex-specific profiles at the onset of the study.
2. Longitudinal Follow-Up: Monitor participants over 18 months to track disease progression and evaluate changes in biomarkers.

Participants:

* Total Enrollment: 210 participants.
* 120 individuals with early-stage PD (60 men, 60 women).
* 90 healthy controls (45 men, 45 women).
* Inclusion Criteria: Participants aged 18-80 years with idiopathic early-stage PD (diagnosed within 3 years), Hoehn \& Yahr stage ≤2.5, or healthy individuals without neurological disorders.
* Exclusion Criteria: Conditions such as major depression, dementia, or premenopausal status (for women).

Procedures:

Participants will undergo:

* Clinical Assessments: Evaluations of motor (e.g., MDS-UPDRS) and non-motor symptoms (e.g., sleep, mood, fatigue scales).
* Blood Tests: Analysis of hormone levels (e.g., testosterone, SHBG) and calculation of the Free Androgen Index.
* Neuroimaging:
* MRI: Examine structural and functional changes in the brain.
* DAT Scans: Assess dopamine transporter binding levels.
* Questionnaires and Interviews: Assess emotional well-being, cognitive function, and quality of life.

Outcome Measures:

* Primary Outcomes: Sex-related differences in clinical and biomarker profiles at baseline and follow-up.
* Secondary Outcomes: Correlations between neuroimaging findings and clinical measures.
* Exploratory Outcomes: Biomarker trajectories over time and their predictive value for disease progression.

Significance:

This study addresses critical gaps in understanding sex-based differences in PD. By integrating clinical, biological, and imaging data, the results could:

* Improve understanding of PD's natural history.
* Highlight the importance of considering sex as a factor in research and treatment design.
* Lead to more personalized and equitable healthcare strategies.

Funding and Ethical Considerations:

The study is funded by the European Union's NextGenerationEU initiative and the Italian Ministry of University and Research (PRIN). It adheres to the Declaration of Helsinki, Good Clinical Practice guidelines, and all relevant regulatory standards. Written informed consent will be obtained from all participants before enrollment.

Implications for Future Research:

Findings from the GENDERIZE-PD study will inform the design of sex-specific clinical trials and potentially contribute to the development of disease-modifying therapies. By considering sex as a key biological variable, this research aims to set a new standard for inclusivity and precision in PD care.

Eligibility criteria: Inclusion Criteria:

Patients with Parkinson's Disease:

* Age: 18-80 years old
* Idiopathic early-stage Parkinson's Disease (≤3 years of disease)
* Stage ≤2.5 on the Hoehn\&Yahr scale Able to give informed consent

Healthy controls:

-Age: 18-80 years old Able to give informed consent

Exclusion Criteria:

* Patients with Parkinson's Disease:
* Presence of Parkinson's Disease dementia
* Presence of major depression or other dysthymic disorders according to DSM-IV criteria
* Women not in menopause (menopause is a point in time 12 months after a woman's last period)
* Any other relevant neurological or medical condition

Healthy controls:

* Women not in menopause (menopause is a point in time 12 months after a woman's last period)
* Any other relevant neurological or medical condition

Primary outcomes:
measure: MDS-sponsored revision of the Unified Parkinson's Disease Rating Scale
timeFrame: 0,6,12, 18 months
Secondary outcomes:
measure: Sex hormones (free androgens index)
timeFrame: Baseline, 12 months
Other outcomes:
measure: Magnetic resonance imaging
timeFrame: 0,12 months
measure: (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ((123)I-FP-CIT) SPECT.
timeFrame: baseline
measure: Unified Dyskinesia Rating Scale (UDysRS)
timeFrame: 0,6,12,18 months
measure: Freezing of Gait Questionnaire (FOGq)
timeFrame: 0,6,12,18 months
measure: Nonmotor Symptom assessment scale for PD (NMSS)
timeFrame: 0,6,12,18 months
measure: Apathy evaluation scale (AES)
timeFrame: 0, 12 months
measure: Parkinson Anxiety Scale (PAS)
timeFrame: 0,12 months
measure: Beck Depression Inventory (BDI)
timeFrame: 0,12 months
measure: Parkinson's Disease Sleep Scale (PDSS)
timeFrame: 0,12 months
measure: Parkinson's Disease Fatigue Scale (PFS)
timeFrame: 0,12 months
measure: Barratt Impulsiveness Scale-11 (BIS-11)
timeFrame: 0, 12 months
measure: Temperament and Character Inventory (TCI)
timeFrame: 0, 12 months
measure: Questionnaire for impulsive-compulsive disorders in Parkinson's disease Rating Scale (QUIP-RS)
timeFrame: 0,12 months
measure: Assessment of Autonomic Dysfunction in Parkinson's Disease (SCOPA-AUT)
timeFrame: 0, 12 months
measure: King's PD Pain Scale (KPPS)
timeFrame: 0,12 months
measure: REM Sleep Behavior Disorder Single Question (RBDSQ)
timeFrame: 0, 12 months
Locations:
Study officials:
affiliation: IRCCS San Raffale, Milan
name: Federica Agosta, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: