Overview
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clinical_trials_auto_1["Background and Clinical Rationale"]
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clinical_trials_auto_2["Autonomic System Overview"]
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clinical_trials_auto_3["Autonomic Features in PSP"]
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clinical_trials_auto_4["Diagnostic Value"]
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clinical_trials_auto_5["Therapeutic Implications"]
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This study characterizes autonomic dysfunction in Progressive Supranuclear Palsy, assessing orthostatic hypotension, urinary dysfunction, and other autonomic features.
Study Details
...Overview
Mermaid diagram (expand to render)
This study characterizes autonomic dysfunction in Progressive Supranuclear Palsy, assessing orthostatic hypotension, urinary dysfunction, and other autonomic features.
Study Details
- NCT Number: NCT06490926
- Status: Recruiting
- Study Type: Observational
- Conditions: PSP, CBS
Background and Clinical Rationale
Autonomic dysfunction is a well-recognized but often underappreciated feature of Progressive Supranuclear Palsy that contributes substantially to patient morbidity and reduced quality of life[@autonomic]. Unlike the characteristic motor symptoms that define PSP, autonomic manifestations can appear early in the disease course and may provide valuable diagnostic clues as well as therapeutic targets.
Autonomic System Overview
The autonomic nervous system regulates involuntary bodily functions through its sympathetic and parasympathetic divisions. In PSP, neurodegeneration affects brainstem and subcortical structures that coordinate autonomic function, leading to dysregulation across multiple organ systems[@low2015].
Autonomic Features in PSP
Cardiovascular Dysregulation: Orthostatic hypotension (a sudden drop in blood pressure upon standing) is one of the most common autonomic manifestations in PSP. Unlike Parkinson's disease where orthostatic hypotension often reflects peripheral autonomic neuropathy, in PSP it results from central autonomic failure related to brainstem involvement[@palma2020].
Urinary Dysfunction: Lower urinary tract symptoms are nearly universal in PSP, including urgency, frequency, nocturia, and often urge incontinence. These symptoms reflect loss of inhibitory control over the micturition reflex, which is mediated by brainstem structures damaged in PSP[@sakakibara2016].
Gastrointestinal Dysmotility: Constipation is extremely common and often precedes motor symptoms by years. Delayed gastric emptying and reduced gut motility result from autonomic dysregulation. Some studies suggest that constipation may be a prodromal marker of PSP[@abbott2001].
Thermoregulatory Dysfunction: Impaired sweating and temperature regulation occur due to sympathetic nervous system involvement. Patients may experience episodes of hypothermia or hyperthermia without appropriate physiological responses.
Diagnostic Value
Autonomic testing may aid in the differential diagnosis of atypical parkinsonism:
- PSP vs. PD: More severe autonomic dysfunction in PSP, particularly earlier orthostatic hypotension
- PSP vs. MSA: Overlapping features but MSA often shows more severe cardiovascular autonomic failure
- PSP vs. CBS: Autonomic dysfunction often more pronounced in PSP
Therapeutic Implications
Understanding autonomic dysfunction in PSP has important treatment implications:
- Orthostatic hypotension management (hydration, salt intake, compression stockings, medications)
- Urinary symptoms management (anticholinergics, behavioral interventions)
- Constipation management (fiber, hydration, laxatives, prokinetics)
- Temperature regulation strategies
Study Objectives
Primary Objectives
Quantify Autonomic Dysfunction Severity: Characterize the spectrum and severity of autonomic dysfunction in PSP using standardized testing protocols.
Correlate with Disease Stage: Establish relationships between autonomic dysfunction severity and disease stage, duration, and progression rate.
Identify Diagnostic Biomarkers: Evaluate whether autonomic measures can serve as diagnostic biomarkers or improve diagnostic accuracy for PSP.
Assess Treatment Response: Establish whether autonomic measures can serve as sensitive endpoints for therapeutic interventions.Secondary Objectives
- Compare autonomic profiles across PSP subtypes (Richardson syndrome vs. variants)
- Evaluate relationships between autonomic and motor/cognitive measures
- Characterize autonomic dysfunction in Corticobasal Syndrome for comparison
- Assess caregiver burden related to autonomic symptoms
Study Design
Study Type and Duration
This is a cross-sectional observational study that evaluates autonomic function in patients with PSP and corticobasal syndrome. Each participant undergoes a single comprehensive autonomic evaluation visit.
Assessment Timeline
The comprehensive assessment is conducted in a single visit lasting approximately 3-4 hours, including:
Baseline vital signs and symptom questionnaires (30 minutes)
Head-up tilt table testing (45-60 minutes)
Heart rate variability testing (30 minutes)
Urinary function assessment (30 minutes)
Additional autonomic tests as indicated (60 minutes)Assessments and Measures
Head-Up Tilt Table Testing
The head-up tilt table test is the gold standard for evaluating orthostatic intolerance and is central to this study[@freeman2011]:
Procedure: After a resting period in the supine position, the table tilts to 70 degrees for up to 30 minutes while continuous monitoring of heart rate and blood pressure occurs.
Measurements:
- Supine baseline heart rate and blood pressure
- Heart rate and blood pressure at 1, 3, 5, 10, 15, 20, and 30 minutes of tilt
- Symptoms during tilt (lightheadedness, dizziness, presyncope)
- Time to symptoms if they occur
Diagnostic Criteria:
- Orthostatic hypotension: ≥20 mmHg systolic or ≥10 mmHg diastolic drop within 3 minutes of standing/tilt
- Initial orthostatic hypotension: transient drop within 10 seconds of standing
- Delayed orthostatic hypotension: drop after 3 minutes
Heart Rate Variability Analysis
Heart rate variability provides a non-invasive window into autonomic function:
Time-Domain Measures:
- SDNN: Standard deviation of NN intervals
- RMSSD: Root mean square of successive differences (reflects parasympathetic activity)
- pNN50: Percentage of successive RR intervals differing by >50 ms
Frequency-Domain Measures:
- Low frequency (LF) power: Reflects combined sympathetic and parasympathetic activity
- High frequency (HF) power: Reflects parasympathetic (vagal) activity
- LF/HF ratio: Reflects sympathetic-parasympathetic balance
Testing Protocol: 5-minute ECG recording during supine rest, followed by assessment of heart rate variability response to standardized breathing (6 breaths/minute).
Urinary Function Assessment
Questionnaires:
- Overactive Bladder Questionnaire (OAB-q)
- International Prostate Symptom Score (IPSS)
- Urinary Incontinence Questionnaire
Voiding Diary: 3-day voiding diary recording timing, volume, and episodes of incontinence
Additional Autonomic Testing
Based on clinical indication, additional testing may include:
- Quantitative Sudomotor Axon Reflex Test (QSART): Evaluates sudomotor function
- Skin Conductance Testing: Assesses sympathetic cholinergic function
- Valsalva Maneuver: Evaluates baroreflex function
- Deep Breathing Test: Assesses parasympathetic-cardiac function
Clinical Correlation Measures
Motor Assessment
- PSP Rating Scale (PSPRS): Comprehensive clinical rating scale for PSP severity
- MDS-UPDRS Parts I-III: Unified Parkinson's Disease Rating Scale
- Hoehn and Yahr Staging: Disease stage classification
- Timed Up and Go Test: Functional mobility assessment
Non-Motor Assessment
- MDS-UPDRS Part I: Non-motor experiences of daily living
- Scales for Outcomes in Parkinson's Disease - Autonomic (SCOPA-AUT): Validated autonomic questionnaire
- Montreal Cognitive Assessment (MoCA): Cognitive screening
- Beck Depression Inventory (BDI): Depression assessment
Quality of Life Measures
- Parkinson's Disease Questionnaire (PDQ-39): Quality of life in Parkinson's disease
- SF-36 Health Survey: Generic quality of life measure
- Caregiver Burden Inventory: Assessment of caregiver stress
Patient Population
Inclusion Criteria
- Clinical diagnosis of PSP (Richardson syndrome or variant) or CBS
- Diagnosis confirmed by movement disorder neurologist
- Ability to undergo autonomic testing including tilt table
- Able to provide informed consent
- Caregiver available to accompany study visit
Exclusion Criteria
- Current urinary tract infection
- Active cardiac conditions affecting blood pressure
- Significant orthopedic limitations preventing tilt table testing
- Contraindications to autonomic testing
- Current treatment with medications that significantly affect autonomic function (unless stable dose for ≥4 weeks)
Statistical Analysis
Sample Size and Power
The study aims to enroll approximately 75 participants with PSP and 25 with CBS. This sample size provides:
- 80% power to detect correlation coefficients of 0.3 between autonomic measures and clinical scales
- Adequate power for subgroup analyses across PSP variants
Primary Analyses
- Descriptive statistics for all autonomic measures
- Correlation between autonomic dysfunction severity and disease measures
- Comparison of autonomic profiles between PSP subtypes and CBS
Secondary Analyses
- Regression analyses identifying predictors of autonomic dysfunction
- Factor analysis to identify autonomic symptom clusters
- ROC curve analysis for diagnostic utility of autonomic measures
Clinical Implications
For Clinical Care
Findings from this study will inform:
- Routine autonomic screening in PSP patients
- Personalized treatment approaches for autonomic symptoms
- Care planning and prognostic counseling
For Clinical Trials
Autonomic measures may serve as:
- Trial endpoints for symptom-directed interventions
- Biomarkers for disease progression
- Enrichment criteria for selecting patient subgroups
- Monitoring measures for treatment response
For Understanding PSP Pathophysiology
Autonomic dysfunction provides insight into:
- Brainstem involvement in PSP
- Disease spread patterns
- Relationship between pathological burden and clinical manifestations
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
References
Unknown, Autonomic Function in PSP - ClinicalTrials.gov (n.d.)
Low DA, et al, Autonomic dysfunction in progressive supranuclear palsy (2015)
Palma JA, et al, Orthostatic hypotension in neurodegenerative diseases: beyond orthostatic hypotension (2020)
Sakakibara R, et al, Urinary dysfunction in progressive supranuclear palsy compared with other parkinsonian syndromes (2016)
Abbott RD, et al, Frequency of bowel movements and future risk of Parkinson's disease (2001)
Freeman R, et al, Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome (2011)