¶ BLAAC PD - Black and African Americans Connections to Parkinson's Disease (NCT06719583)
Status: Recruiting
Type: Observational
Sponsor: Michael J. Fox Foundation
Enrollment: 500 participants
Study Start: January 2024
Estimated Completion: December 2027
¶ Overview
BLAAC PD (Black and African Americans Connections to Parkinson's Disease) is an observational study led by the Michael J. Fox Foundation addressing critical health disparities in Parkinson's disease research. This study focuses on understanding how Parkinson's disease affects Black and African American communities, with the goal of improving representation in PD research and addressing healthcare inequities.
¶ Background
¶ Health Disparities in Parkinson's Disease
Historical underrepresentation of minority populations in PD research has created significant knowledge gaps:
- Limited data: Most PD studies are conducted in predominantly white cohorts
- Genetic diversity: Lack of representation limits understanding of genetic factors
- Clinical presentation: Possible differences in symptom presentation
- Treatment access: Disparities in diagnosis and treatment
¶ The Need for BLAAC PD
This study addresses:
- Representation: Ensuring Black and African American participation in PD research
- Data collection: Gathering comprehensive clinical data from underrepresented populations
- Genetic characterization: Understanding genetic contributors in diverse populations
- Access barriers: Identifying and addressing barriers to research participation
¶ Study Design
| Parameter | Value |
|---|---|
| Design | Cross-sectional and longitudinal observational |
| Focus | Health disparities in Black/African American PD patients |
| Arms | PD patients vs. healthy controls |
| Duration | 3-year enrollment and follow-up |
¶ Inclusion Criteria
- Race/Ethnicity: Self-identified Black or African American
- Age: 40 years and older
- Diagnosis: Parkinson's disease (research criteria) or healthy control
- Ability to participate: Can complete study assessments
¶ Exclusion Criteria
- Secondary Parkinsonism: Parkinson-plus syndromes
- Medical conditions: Significant comorbidities affecting participation
- Cognitive impairment: Severe dementia preventing consent
¶ Study Objectives
¶ Primary Objectives
- Recruitment: Enroll 500 Black/African American participants
- Characterization: Detailed clinical characterization of PD in this population
- Genetics: Genetic analysis to identify population-specific variants
- Biomarkers: Collection of biosamples for biomarker development
¶ Secondary Objectives
- Compare phenotypes: Compare PD presentation to white cohorts
- Barriers assessment: Identify barriers to research participation
- Care access: Assess diagnostic delay and treatment access
- Education: Develop culturally appropriate educational materials
¶ Data Collection
¶ Clinical Assessments
- Motor function: MDS-UPDRS motor examination
- Non-motor symptoms: Cognition, mood, sleep, autonomic function
- Quality of life: PDQ-39, other patient-reported outcomes
- Medical history: Detailed symptom and treatment history
¶ Biosamples
- Blood: DNA, plasma, serum
- CSF: Cerebrospinal fluid (subset)
- Saliva: For biomarker studies
¶ Additional Data
- Genetics: Whole genome sequencing
- Imaging: MRI (subset)
- Environmental exposures: Lifestyle and occupational history
¶ Scientific Impact
¶ Importance of Diversity in PD Research
Understanding PD in diverse populations:
- Genetic insights: Different genetic backgrounds may reveal novel risk factors
- Clinical variation: May identify different phenotype presentations
- Treatment response: Understanding response differences
- Health disparities: Identifying and addressing healthcare inequities
¶ Expected Outcomes
- Representative cohort: First large-scale Black/African American PD cohort
- Genetic data: Population-specific genetic variants
- Clinical phenotyping: Characterize PD presentation in this population
- Future trials: Infrastructure for future clinical trial inclusion
¶ Michael J. Fox Foundation for Parkinson's Disease Research
The Michael J. Fox Foundation (MJFF) is the world's leading nonprofit funder of Parkinson's disease research, having invested over $1.5 billion since its founding in 2000. The foundation's mission is to find a cure for Parkinson's disease through funded research and clinical trial infrastructure development.
¶ Foundation Programs
Fox Insight: MJFF's flagship patient registry program that collects self-reported data from individuals with Parkinson's disease and healthy controls. This massive longitudinal dataset provides valuable phenotypic information for research.
Clinical Trial Readiness Programs: The foundation has established networks of clinical trial sites prepared to conduct PD research, reducing startup time for new studies.
The Parkinson's Progression Markers Initiative (PPMI): A landmark biomarker study that has enrolled over 1,500 participants including individuals with PD, at-risk carriers of PD genes, and healthy controls.
¶ MJFF Research Priorities
- Alpha-synuclein research: Funding therapeutic approaches targeting alpha-synuclein aggregation
- Genetic causes of PD: Supporting research into LRRK2, GBA, SNCA, and other PD-associated genes
- Biomarker development: Finding objective measures of disease progression and treatment response
- Neuroprotective therapies: Developing disease-modifying treatments
- Precision medicine: Tailoring treatments to individual genetic profiles
¶ Foundation Impact on Clinical Trials
The Michael J. Fox Foundation has been instrumental in advancing PD clinical trials:
- De-risking research: Providing funding for early-stage projects that might not otherwise receive support
- Patient engagement: Building a community of engaged research participants through Fox Insight
- Data sharing: Creating open-access datasets that accelerate research
- Regulatory engagement: Working with FDA to advance drug development endpoints
¶ Study Design Details
¶ Cross-Sectional Assessment Protocol
The cross-sectional component establishes baseline characteristics:
- Visit 1 (Screening): Consent, eligibility verification, basic demographics
- Visit 2 (Baseline): Complete motor and non-motor assessments, biosample collection
- Optional Visit 3: Imaging substudy participants
¶ Longitudinal Follow-Up Protocol
Participants are followed over the 3-year study period:
- Month 6: Brief telephone assessment
- Year 1: In-person comprehensive assessment
- Year 2: In-person comprehensive assessment
- Year 3: In-person comprehensive assessment and study completion
¶ Biosample Processing and Storage
All collected biosamples follow standardized protocols:
Blood Processing:
- Whole blood collected in EDTA tubes for plasma separation
- Whole blood collected in PAXgene tubes for RNA isolation
- Serum separator tubes for biomarker studies
- Processing within 2 hours of collection
- Aliquoted and stored at -80°C
CSF Collection Protocol:
- Lumbar puncture performed by trained neurologists
- Collection in polypropylene tubes
- Centrifugation within 1 hour
- Stored in 0.5 mL aliquots at -80°C
- Dedicated for biomarker analysis
DNA Extraction and Genotyping:
- Standard salting-out method or automated extraction
- Whole genome sequencing for all participants
- Quality control metrics for sample integrity
- Population stratification analysis
¶ Statistical Considerations
Power Analysis:
- Target enrollment of 500 provides 80% power to detect effect sizes of 0.25 with α=0.05
- Allows for subgroup analyses by genetic status
- Provides adequate sample for novel variant discovery
Primary Analyses:
- Descriptive statistics for all demographic and clinical variables
- Comparison of PD phenotypes with published white cohort data
- Genetic variant frequency estimation
¶ Clinical Phenotyping Details
¶ Motor Assessment Battery
The motor examination follows MDS-UPDRS Part III standardized protocol:
Assessment Components:
- Speech evaluation (item 1)
- Facial expression (item 2)
- Rigidity assessment (items 3-6)
- Finger tapping (items 7-10)
- Hand movements (items 11-14)
- Pronation-supination (items 15-18)
- Toe tapping (items 19-22)
- Leg agility (items 23-26)
- Arising from chair (item 27)
- Gait (items 28-30)
- Freezing of gait (item 31)
- Postural stability (item 32)
- Postural tremor (item 33)
- Kinetic tremor (items 34-38)
Assessment Conditions:
- OFF medication assessment (withdrawal ≥12 hours)
- ON medication assessment (1-2 hours after usual medication)
- Video recording for central reading (subset)
¶ Non-Motor Assessment Battery
Cognitive Assessment:
- Montreal Cognitive Assessment (MoCA)
- Trail Making Test A and B
- Digit Span Forward and Backward
- Word List Learning and Recall
Psychiatric Assessment:
- Beck Depression Inventory (BDI-II)
- State-Trait Anxiety Inventory (STAI)
- Parkinson's Disease Questionnaire (PDQ-39) - emotional well-being subdomain
- Apathy Evaluation Scale
Sleep Assessment:
- Parkinson's Disease Sleep Scale (PDSS-2)
- Epworth Sleepiness Scale (ESS)
- REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
Autonomic Assessment:
- Orthostatic blood pressure measurements
- urinary symptom questionnaire
- gastrointestinal symptom inventory
¶ Quality of Life Measures
PDQ-39:
- 39 items across 8 domains
- Mobility, activities of daily living, emotional well-being, stigma, social support, communication, bodily discomfort, cognition
- Standardized to 0-100 scale
SF-36:
- Generic health status measure
- Physical and mental component scores
- Allows comparison with general population
¶ Genetic Analysis Plan
¶ Whole Genome Sequencing Protocol
Sequencing Parameters:
- 30x coverage minimum
- Illumina NovaSeq or equivalent platform
- Alignment to GRCh38 reference
- Variant calling following GATK best practices
Quality Control:
- Sample-level: call rate >98%, contamination
% - Variant-level: genotype quality score >30, read depth >10
- Population outliers identified via PCA
¶ Variant Annotation and Interpretation
Computational Tools:
- ANNOVAR for functional annotation
- SIFT and PolyPhen for pathogenicity prediction
- CADD for variant deleteriousness scoring
- ClinVar database for known pathogenic variants
Variant Classification:
- Pathogenic, Likely Pathogenic, Variant of Uncertain Significance (VUS), Likely Benign, Benign
- Following ACMG guidelines
¶ Gene-Specific Analysis
PD-Associated Genes:
- LRRK2: G2019S, R1441C/H/G, N1437H, Y1699C
- GBA: N409S, L444P, E326K, T369M
- SNCA: A53T, A30P, duplications
- PARK2 (parkin), PARK7 (DJ-1), PINK1, ATP13A2
- VPS35: D620N
- DNAJC13, RAB39B, SYNJ1
Additional Analysis:
- Polygenic risk score calculation
- Novel gene discovery in familial cases
- Founder mutation identification
¶ Health Equity and Research Design
¶ Historical Context
Underrepresentation in PD Research:
- Prior to 2020, less than 5% of PD clinical trial participants were from minority populations
- Genetic studies heavily biased toward European ancestry
- Clinical phenotypic data primarily from white cohorts
- Healthcare access disparities affect diagnosis and treatment
¶ Barriers to Participation
Identified Barriers:
- Geographic: Trial sites concentrated in major academic centers
- Financial: Indirect costs of participation (transportation, time off work)
- Cultural: Mistrust of medical research, lack of culturally appropriate materials
- Logistical: Childcare, work schedules, transportation
- Knowledge: Limited awareness of research opportunities
¶ Study Solutions
BLAAC PD Addressing Barriers:
- Site selection in areas with significant Black populations
- Community-based recruitment through churches and community organizations
- Flexible scheduling including evening and weekend appointments
- Reimbursement for travel and time
- Culturally sensitive study staff and materials
- Partnerships with Black neurologists and healthcare providers
¶ Community Engagement
Stakeholder Engagement:
- Advisory board including Black PD patients and caregivers
- Community advisory councils in each study region
- Focus groups to inform study design and recruitment strategies
- Patient navigation support throughout study participation
¶ Scientific Impact and Future Directions
¶ Anticipated Scientific Contributions
1. Genetic Data:
- First large-scale whole genome sequencing dataset from Black PD patients
- Novel variant discovery in known PD genes
- Population-specific risk allele identification
- Refinement of polygenic risk scores for this population
2. Clinical Phenotypic Data:
- Comprehensive characterization of PD symptoms in Black patients
- Comparison with white cohorts to identify similarities and differences
- Identification of potential phenotype modifiers by ancestry
- Natural history data specific to this population
3. Healthcare Access Data:
- Diagnostic delay patterns
- Treatment utilization patterns
- Barriers to specialist care
- Healthcare outcomes in under-resourced settings
¶ Building Research Infrastructure
Long-term Impact:
- Establish network for future clinical trial inclusion
- Train researchers in culturally competent approaches
- Create repository of biosamples for future studies
- Develop model for inclusion of other underrepresented populations
¶ Future Clinical Trial Applications
Trial Design Implications:
- Understand potential treatment response differences
- Develop ancestry-appropriate outcome measures
- Ensure generalizability of therapeutic benefits
- Reduce health disparities in PD care
¶ Related Pages
- Parkinson's Disease
- Parkinson's Disease Genetics
- LRRK2 Gene and Parkinson's Disease
- GBA Gene and Parkinson's Disease
- Health Disparities in Neurodegeneration
- PD Epidemiology
- Michael J. Fox Foundation
- Clinical Trials in Parkinson's Disease
- Fox Insight Registry