<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">CBS/PSP Clinical Trials Guide</th>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT05297202</td>
<td>Lithium for PSP — Phase 2 Trial</td>
</tr>
<tr>
<td class="label">NCT02795052</td>
<td>Neurologic Stem Cell Treatment Study</td>
</tr>
<tr>
<td class="label">NCT03174938</td>
<td>The Swedish BioFINDER 2 Study</td>
</tr>
<tr>
<td class="label">NCT02994719</td>
<td>Gait Analysis in Neurological Disease</td>
</tr>
<tr>
<td class="label">NCT06174948</td>
<td>CUE1/CUE1+ in Parkinson's and Related Disorders</td>
</tr>
<tr>
<td class="label">NCT07348276</td>
<td>4R Tau Ligands PET Tracers</td>
</tr>
<tr>
<td class="label">NCT06647641</td>
<td>The CurePSP Genetics Program</td>
</tr>
<tr>
<td class="label">NCT06162013</td>
<td>NADAPT Study - NAD Replenishment for Atypical Parkinsonism</td>
</tr>
<tr>
<td class="label">NCT06596746</td>
<td>MARKERS-NDD Progression Markers</td>
</tr>
<tr>
<td class="label">NCT04468932</td>
<td>Transcranial Magnetic Stimulation in PSP</td>
</tr>
<tr>
<td class="label">NCT04706234</td>
<td>Laryngopharyngeal Function Assessment</td>
</tr>
<tr>
<td class="label">NCT03638505</td>
<td>Quality of Life and Caregiver Burden in PSP</td>
</tr>
<tr>
<td class="label">NCT06613204</td>
<td>STELLA-FTD: Behavior Intervention for FTD Care
<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">CBS/PSP Clinical Trials Guide</th>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT05297202</td>
<td>Lithium for PSP — Phase 2 Trial</td>
</tr>
<tr>
<td class="label">NCT02795052</td>
<td>Neurologic Stem Cell Treatment Study</td>
</tr>
<tr>
<td class="label">NCT03174938</td>
<td>The Swedish BioFINDER 2 Study</td>
</tr>
<tr>
<td class="label">NCT02994719</td>
<td>Gait Analysis in Neurological Disease</td>
</tr>
<tr>
<td class="label">NCT06174948</td>
<td>CUE1/CUE1+ in Parkinson's and Related Disorders</td>
</tr>
<tr>
<td class="label">NCT07348276</td>
<td>4R Tau Ligands PET Tracers</td>
</tr>
<tr>
<td class="label">NCT06647641</td>
<td>The CurePSP Genetics Program</td>
</tr>
<tr>
<td class="label">NCT06162013</td>
<td>NADAPT Study - NAD Replenishment for Atypical Parkinsonism</td>
</tr>
<tr>
<td class="label">NCT06596746</td>
<td>MARKERS-NDD Progression Markers</td>
</tr>
<tr>
<td class="label">NCT04468932</td>
<td>Transcranial Magnetic Stimulation in PSP</td>
</tr>
<tr>
<td class="label">NCT04706234</td>
<td>Laryngopharyngeal Function Assessment</td>
</tr>
<tr>
<td class="label">NCT03638505</td>
<td>Quality of Life and Caregiver Burden in PSP</td>
</tr>
<tr>
<td class="label">NCT06613204</td>
<td>STELLA-FTD: Behavior Intervention for FTD Care Partners</td>
</tr>
<tr>
<td class="label">NCT07136844</td>
<td>Gait and Upper Limb Evaluation</td>
</tr>
<tr>
<td class="label">NCT03872102</td>
<td>Neuroimaging for Parkinsonian Syndromes</td>
</tr>
<tr>
<td class="label">NCT07392411</td>
<td>AI-Based Facial/Speech Patterns in PD</td>
</tr>
<tr>
<td class="label">NCT02605785</td>
<td>Molecular Anatomic Imaging of Tau in PSP</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT03625128</td>
<td>18F-PM-PBB3 PET Study in Tauopathy</td>
</tr>
<tr>
<td class="label">NCT00385710</td>
<td>Valproic Acid in PSP</td>
</tr>
<tr>
<td class="label">NCT04539041</td>
<td>NIO752 Antisense Oligonucleotide</td>
</tr>
<tr>
<td class="label">NCT04715750</td>
<td>[18F]PI-2620 PET Imaging</td>
</tr>
<tr>
<td class="label">NCT05067192</td>
<td>Alpha-synuclein PET Tracer</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT02994719</td>
<td>Gait Analysis in Neurological Disease</td>
</tr>
<tr>
<td class="label">NCT06174948</td>
<td>CUE1/CUE1+ Device Study</td>
</tr>
<tr>
<td class="label">NCT07000851</td>
<td>Imaging Studies in Corticobasal Syndrome</td>
</tr>
<tr>
<td class="label">NCT06596746</td>
<td>MARKERS-NDD Progression Markers</td>
</tr>
<tr>
<td class="label">NCT06162013</td>
<td>NADAPT Study: NAD Replenishment Therapy</td>
</tr>
<tr>
<td class="label">NCT07291687</td>
<td>tDCS as Treatment for Motor Function</td>
</tr>
<tr>
<td class="label">NCT05653778</td>
<td>Scrambler Therapy for CBS Pain</td>
</tr>
<tr>
<td class="label">NCT03225144</td>
<td>Investigating Complex Neurodegenerative Disorders</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT02795052</td>
<td>Neurologic Stem Cell Treatment</td>
</tr>
<tr>
<td class="label">NCT03174938</td>
<td>Swedish BioFINDER 2</td>
</tr>
<tr>
<td class="label">NCT07348276</td>
<td>4R Tau Ligands PET</td>
</tr>
<tr>
<td class="label">NCT07105384</td>
<td>18F-PI-2620 Quantification</td>
</tr>
<tr>
<td class="label">NCT06162013</td>
<td>NADAPT Study: NAD Replenishment</td>
</tr>
<tr>
<td class="label">NCT06596746</td>
<td>MARKERS-NDD Progression</td>
</tr>
<tr>
<td class="label">NCT04468932</td>
<td>TMS in PSP</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT04468932</td>
<td>Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy</td>
</tr>
<tr>
<td class="label">NCT07348276</td>
<td>First-in-Human Study for 4R Tau Ligands (PET Tracers)</td>
</tr>
<tr>
<td class="label">NCT06162013</td>
<td>NADAPT Study: NAD Replenishment Therapy for Atypical Parkinsonism</td>
</tr>
<tr>
<td class="label">NCT07136844</td>
<td>Gait Analysis and Upper Limb Evaluation in Neurological Disease</td>
</tr>
<tr>
<td class="label">NCT06906276</td>
<td>Brain Activity During Complex Walking in Atypical Parkinsonian Syndromes</td>
</tr>
<tr>
<td class="label">NCT06645626</td>
<td>Utilisation of Health Services and Quality of Life in Atypical Parkinsonian Syndromes</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT07000851</td>
<td>Imaging Studies in Corticobasal Syndrome</td>
</tr>
<tr>
<td class="label">NCT02994719</td>
<td>Gait Analysis in Neurological Disease</td>
</tr>
<tr>
<td class="label">NCT07291687</td>
<td>tDCS as Treatment for Motor Function in Neurodegenerative Diseases</td>
</tr>
<tr>
<td class="label">NCT05653778</td>
<td>Scrambler Therapy for CBS Pain</td>
</tr>
<tr>
<td class="label">NCT06596746</td>
<td>MARKERS-NDD Progression Markers</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06618872</td>
<td>Tau-PET With [18F]RO948 vs Amyloid-PET</td>
</tr>
<tr>
<td class="label">NCT06690983</td>
<td>Tau PET/CT in Various Tau-Related Disease Patients</td>
</tr>
<tr>
<td class="label">NCT03372317</td>
<td>Tau PET in Imaging and Cognition: Healthy Adults 55-90</td>
</tr>
<tr>
<td class="label">NCT06120049</td>
<td>[18F]-MFBG vs [123I]-MIBG and [18F]-PE2I in PD vs MSA and DLB vs AD</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT01818661</td>
<td>Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech</td>
</tr>
<tr>
<td class="label">NCT03313011</td>
<td>The Neurobiology of Two Distinct Types of Progressive Apraxia of Speech</td>
</tr>
<tr>
<td class="label">NCT05741853</td>
<td>Cognitive Reserve and Response to Speech-Language Intervention in Bilingual Speakers With PPA</td>
</tr>
<tr>
<td class="label">NCT05558709</td>
<td>Social-cognitive Functioning: Validation of a New Neuropsychological Test</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06765733</td>
<td>Safety and Preliminary Efficacy of Aleeto in MSA Patients</td>
</tr>
<tr>
<td class="label">NCT06890377</td>
<td>Targeted α-synuclein PET Imaging in the Diagnosis of MSA</td>
</tr>
<tr>
<td class="label">NCT06831500</td>
<td>Effect of Carbidopa/Levodopa Ratio on Orthostatic Hypotension in MSA-P and PD</td>
</tr>
<tr>
<td class="label">NCT04782284</td>
<td>Comprehensive Swallowing Rehabilitation in Patients With MSA</td>
</tr>
<tr>
<td class="label">NCT03811808</td>
<td>Multiple System Atrophy Multidisciplinary Clinic</td>
</tr>
<tr>
<td class="label">NCT07324330</td>
<td>Slowing Cognitive Decline in Alpha-synucleinopathies by Enhancing Physical Activity</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06501469</td>
<td>Biomarkers in Parkinsonian Syndromes</td>
</tr>
<tr>
<td class="label">NCT06490926</td>
<td>NMR Metabolomic Study of Serum Biomarkers in PD and Atypical Parkinsonian Syndrome</td>
</tr>
<tr>
<td class="label">NCT06529744</td>
<td>Improving Prognostic Confidence in Neurodegenerative Diseases Using Peripheral Biomarkers</td>
</tr>
<tr>
<td class="label">NCT04715399</td>
<td>UPenn Observational Research Repository on Neurodegenerative Disease (UNICORN)</td>
</tr>
<tr>
<td class="label">NCT04363684</td>
<td>ALLFTD: ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration</td>
</tr>
<tr>
<td class="label">NCT02964637</td>
<td>Diagnosing Frontotemporal Lobar Degeneration</td>
</tr>
<tr>
<td class="label">NCT03225144</td>
<td>Investigating Complex Neurodegenerative Disorders Related to ALS and FTD</td>
</tr>
<tr>
<td class="label">NCT06932809</td>
<td>Study of Biodistribution and Brain Uptake of 18F-JSS20-183A Tau PET Tracer</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06203106</td>
<td>NYSCF Scientific Discovery Biobank</td>
</tr>
<tr>
<td class="label">NCT06595212</td>
<td>Genetics and Environment in the ALS-FTD Spectrum</td>
</tr>
<tr>
<td class="label">NCT06490822</td>
<td>The Skin as a Window to the CNS in Frontotemporal Lobar Degeneration</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT02194816</td>
<td>Modifiable Variables in Parkinsonism (MVP)</td>
</tr>
<tr>
<td class="label">NCT06949865</td>
<td>AI-Enhanced Optimization of Acute Levodopa Challenge Test</td>
</tr>
<tr>
<td class="label">NCT07122908</td>
<td>Effect of Repetitive TMS on Cognitive Improvement in Dementia With Lewy Bodies</td>
</tr>
<tr>
<td class="label">NCT05014971</td>
<td>Telehealth in Lewy Body Dementia</td>
</tr>
<tr>
<td class="label">NCT05911932</td>
<td>Investigating Genetic Status in Patients Presenting to Clinic</td>
</tr>
<tr>
<td class="label">NCT04389437</td>
<td>OCT-Angiography and Adaptive Optics in Patients With Memory Impairment</td>
</tr>
<tr>
<td class="label">NCT06439355</td>
<td>Gustation in Idiopathic Parkinson's Disease and Lewy Body Disease</td>
</tr>
<tr>
<td class="label">NCT06057909</td>
<td>Neurodegeneration and Neuronal Fluctuations in Lewy Body Disease and AD</td>
</tr>
<tr>
<td class="label">NCT05121012</td>
<td>Synaptic Loss in Multiple System Atrophy</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06174948</td>
<td>CUE1/CUE1+ Device for Gait Freezing in Parkinson's and Related Disorders</td>
</tr>
<tr>
<td class="label">NCT07022522</td>
<td>Frequency-specific Subthalamic Nucleus Stimulation on Inhibitory Control in PD</td>
</tr>
<tr>
<td class="label">NCT06920134</td>
<td>Epidural Electrical Stimulation for Hemodynamic Management in PD</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06647641</td>
<td>CurePSP Genetics Program</td>
</tr>
<tr>
<td class="label">NCT01793168</td>
<td>Rare Disease Patient Registry & Natural History Study (Sanford)</td>
</tr>
<tr>
<td class="label">NCT Number</td>
<td>Title</td>
</tr>
<tr>
<td class="label">NCT06322667</td>
<td>Post Marketing Study in Early AD Treated With Lecanemab</td>
</tr>
<tr>
<td class="label">NCT06923007</td>
<td>Alzheimer's Disease Treated With Vagus Nerve Stimulation</td>
</tr>
<tr>
<td class="label">NCT03821857</td>
<td>Sex-Specific Effects of Endocrine Disruption on Aging and AD</td>
</tr>
<tr>
<td class="label">NCT07011745</td>
<td>KarXT + KarX-EC for Agitation in AD (ADAGIO-2)</td>
</tr>
</table>
Clinical Trials Guide for Corticobasal Degeneration and Progressive Supranuclear Palsy
This guide provides comprehensive information for patients, caregivers, and clinicians seeking to participate in or learn about clinical trials for corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). These rare neurodegenerative disorders have limited treatment options, making clinical trial participation crucial for advancing therapeutic development.[@litvan2017][@armstrong2013][@hoglinger2021][@stamelou2022]
Clinical trials offer access to experimental treatments while contributing to scientific understanding of these conditions.[@clinicaltrialsgov][@curepsp] This guide covers trial search strategies, active trials, enrollment considerations, and resources for connecting with research programs.[@stamelou2022][@ghebremichael2022]
Clinical trials proceed through distinct phases, each serving specific purposes in evaluating safety and efficacy.[@clinicaltrialsgov]
Phase 1 trials focus on safety, enrolling a small number of participants (typically 20-80) to evaluate side effects and determine appropriate dosing. These trials primarily assess tolerability and pharmacokinetics.[@clinicaltrialsgov]
Phase 2 trials expand enrollment (typically 100-300 participants) to further evaluate efficacy and continue safety assessment. These trials often use placebo controls and may include dose-response studies.[@clinicaltrialsgov]
Phase 3 trials confirm effectiveness, monitor side effects, and compare the experimental treatment to standard care. These larger trials (typically 1,000-3,000 participants) provide the primary evidence for regulatory approval.[@clinicaltrialsgov]
Phase 4 trials occur after FDA approval and monitor long-term safety in broader populations.[@clinicaltrialsgov]
[ClinicalTrials.gov](https://clinicaltrials.gov) serves as the primary registry for clinical trials worldwide. Effective search strategies for CBD and PSP include:[@clinicaltrialsgov]
NCT05297202 - Lithium for PSP — Phase 2 Trial
This Phase 2 trial evaluates low-dose lithium as a disease-modifying treatment for PSP. Lithium inhibits glycogen synthase kinase-3 beta (GSK-3β), a kinase that hyperphosphorylates tau protein, promoting its aggregation into neurofibrillary tangles. The trial targets serum lithium levels of 0.6-0.8 mEq/L to achieve CNS penetration while minimizing mood-related side effects. Primary endpoint is change in PSP Rating Scale (PSPRS) at 12 months. See [Lithium for PSP — Phase 2 Trial](/clinical-trials/lithium-psp-phase-2-nct05297202) for detailed mechanism and eligibility.
NCT02994719 - Gait Analysis in Neurological Disease
This observational study analyzes gait patterns in patients with atypical parkinsonism including corticobasal syndrome. The study uses wearable sensors to quantify movement characteristics and may help identify biomarkers for disease progression.[@nct]
NCT06174948 - CUE1/CUE1+ Device Study
This device trial evaluates the CUE1 vibrotactile cueing device in patients with Parkinson's disease and related disorders. While primarily targeting PD, the device may benefit CBS patients with gait freezing and movement initiation difficulties.[@ncta]
NCT07348276 - First-in-Human Tau Ligand Study
This early Phase 1 trial evaluates two novel 4R tau PET radioligands ([18F]ABBV-964i and [18F]ABBV-965i) for imaging tau protein in the brain. These tracers may enable earlier diagnosis and better monitoring of disease progression in 4R tauopathies including CBS and PSP.[@nctb]
NCT06647641 - The CurePSP Genetics Program
This observational prospective genetic study aims to obtain DNA for research and testing from patients with PSP, CBS, MSA, and related neurological conditions and their families. Up to 1,000 adults with clinically diagnosed PSP, CBS, MSA, or related conditions will be enrolled. The study involves sequencing of participant blood samples to identify genetic factors that may influence disease risk, progression, and treatment response.
NCT06162013 - NADAPT Study (NAD Replenishment for Atypical Parkinsonism)
This Phase 2 randomized double-blind trial evaluates NAD replenishment therapy for patients with atypical parkinsonism including PSP, MSA, and CBS. The study investigates whether increasing NAD+ levels through supplementation can slow disease progression in these severe neurodegenerative conditions. Given the strong preclinical evidence for NAD+ depletion in PSP and CBS and the role of NAD+ in mitochondrial function and cellular repair, this trial represents an important disease-modifying approach.
NCT02795052 - Neurologic Stem Cell Treatment Study
This Phase 1 trial evaluates the safety of intravenous and intrathecal administration of neural stem cells for patients with progressive supranuclear palsy and corticobasal degeneration. The study assesses adverse events and preliminary efficacy measures over 24 months of follow-up.[@pascual2021]
NCT03174938 - Swedish BioFINDER 2 Study
This observational study characterizes biomarkers and clinical features in patients with neurodegenerative diseases, including PSP.[@wen2021][@sanchez2019][@schott2021] The study includes cerebrospinal fluid sampling, PET imaging, and comprehensive neurological assessments.
NCT04706234 - Laryngopharyngeal Function Assessment
This observational study systematically assesses laryngeal and pharyngeal function in patients with neurodegenerative diseases including PSP. Using fiberoptic endoscopic evaluation of swallowing (FEES), researchers aim to characterize dysphagia patterns and develop better management strategies. This is particularly relevant for PSP patients who often develop life-threatening swallowing difficulties.[@ncti]
NCT03638505 - Quality of Life and Caregiver Burden in PSP
This French observational study focuses on quality of life for PSP patients and the burden on caregivers. Given the significant impact of PSP on both patients and families, understanding these factors is crucial for developing comprehensive care approaches. The study may inform support strategies and intervention planning.[@nctj]
NCT07136844 - Gait and Upper Limb Evaluation (ActiLiège-Adult)
This Belgian observational study collects natural history data on gait parameters and upper limb function in patients with neurological diseases. While targeting multiple conditions, the standardized assessment protocols may yield insights applicable to PSP and CBS patients. The study uses quantitative movement analysis to track disease progression.[@nctk]
NCT03872102 - Neuroimaging for Parkinsonian Syndromes
This French study aims to identify neuroimaging biomarkers that can differentiate Parkinson's disease from atypical parkinsonism (including PSP and CBS) and predict progression rates. Using advanced MRI techniques, researchers seek to improve diagnostic accuracy and prognostic capabilities—critical needs given the clinical overlap between these conditions.[@nctl]
NCT07392411 - AI-Based Facial/Speech Patterns
This Chinese study employs artificial intelligence to analyze facial expressions and speech patterns in Parkinson's disease and related disorders. Digital biomarkers derived from these analyses may aid in early diagnosis and disease differentiation. The approach could potentially be applied to CBS and PSP as well.[@nctm]
NCT02605785 - Molecular Anatomic Imaging of Tau in PSP
This Phase 2 study uses PET imaging to visualize tau protein distribution in the brains of PSP patients. Understanding tau burden and its correlation with clinical symptoms may help guide therapeutic development and patient stratification for clinical trials.[@nctn]
NCT03225144 - Investigating Complex Neurodegenerative Disorders
This observational study investigates the genetic and clinical features of complex neurodegenerative disorders, including FTLD spectrum disorders. The study may include CBS patients and aims to better understand disease mechanisms and identify potential therapeutic targets.[@ncto]
NCT02994719 - Gait Analysis in Neurological Disease
This observational study at Beth Israel Deaconess Medical Center uses wearable sensors to analyze gait patterns in patients with atypical parkinsonism including corticobasal syndrome. The study aims to identify quantitative movement biomarkers that could aid in diagnosis and track disease progression.
NCT06174948 - CUE1/CUE1+ Device Study
This device study at Queen Mary University of London evaluates a vibrotactile cueing device for gait freezing in Parkinson's disease and related disorders. While primarily focused on PD, the device may benefit CBS patients experiencing movement initiation difficulties.
NCT07000851 - Imaging Studies in Corticobasal Syndrome
This observational study investigates neuroinflammation and white matter damage in corticobasal syndrome using advanced imaging techniques. The study aims to determine whether these pathological processes are interrelated and how they contribute to disease progression. Understanding neuroinflammation in CBS may lead to new therapeutic targets.
NCT06596746 - MARKERS-NDD Study
The MARKERS-NDD is a prospective, observational, longitudinal study collecting data from patients with various neurodegenerative diseases followed longitudinally for routine examinations. This study aims to identify progression markers that can be used to track disease advancement and response to treatment.
NCT06162013 - NADAPT Study
The NADAPT Study is a Phase 2 randomized double-blind trial evaluating NAD replenishment therapy for atypical parkinsonian syndromes including PSP, MSA, and CBS. This trial targets cellular energy metabolism, which is impaired in these rapidly progressive neurodegenerative disorders. Patients with PSP, MSA, or CBS may be eligible.
NCT07291687 - tDCS for Motor Function
This device study evaluates transcranial direct current stimulation (tDCS) as a treatment for motor function in neurodegenerative diseases. tDCS is a non-invasive brain stimulation technique that may improve motor symptoms by modulating cortical excitability. The study combines tDCS with motor training.
NCT05653778 - Scrambler Therapy for CBS Pain
This pilot trial tests whether scrambler therapy is an effective treatment for neuropathic pain in patients with corticobasal syndrome. Scrambler therapy is a non-invasive neuromodulation technique that uses electrical signals to replace pain with non-painful sensations. This addresses a significant quality-of-life issue in CBS patients.
Many clinical trials enroll patients with either CBS or PSP since both are 4R tauopathies with similar pathological mechanisms:
Trial eligibility depends on specific criteria designed to ensure participant safety and scientific validity:
Diagnostic criteria: Most trials require confirmed diagnosis by specific clinical criteria (e.g., NINDS PSP criteria or MDS criteria for PSP; Armstrong criteria for CBD).[@litvan2017][@armstrong2013][@roemer2018][@coughlin2022][@stamelou2020]
Disease stage: Trials typically enroll patients at specific disease stages. Early-stage patients may qualify for disease-modifying trials, while later-stage patients may be eligible for symptomatic treatment studies.[@hoglinger2021][@stamelou2022][@williams2005]
Age requirements: Most trials require participants be between 40-85 years old, though criteria vary by study.[@ghebremichael2022]
Exclusion criteria: Common exclusions include significant medical comorbidities, prior deep brain stimulation, participation in other trials within specified timeframes, and contraindicated medications.[@hoglinger2021][@ghebremichael2022]
Many trials require multiple visits over extended periods. Consider:
Mayo Clinic (Rochester, Minnesota)
The Mayo Clinic PSP research program includes Dr. Bradley Boeve and colleagues, conducting clinical trials and biomarker studies. Contact: [Mayo Clinic Neurology](https://www.mayoclinic.org/departments-centers/neurology)
University of California, San Francisco (UCSF)
UCSF Memory and Aging Center conducts PSP research under Dr. Bruce Miller. The center participates in multiple clinical trials and observational studies. Contact: [UCSF Memory and Aging Center](https://memory.ucsf.edu)
University of Pennsylvania
Penn's PSP research program includes the Penn FTLD Center, conducting therapeutic trials and biomarker studies. Contact: [Penn Neurology](https://www.pennmedicine.org/neurology)
University of British Columbia
The Pacific Parkinson's Research Centre conducts PSP studies. Contact: [PPRC](https://www.parkinson.ca)
Swedish BioFINDER 2 (Lund, Sweden)
The Swedish BioFINDER study, led by Dr. Oskar Hansson, conducts PSP research including biomarker studies and clinical trials.
University College London (UCL)
The UCL Dementia Research Centre conducts PSP research, including trials targeting tau pathology.
Tokyo Metropolitan Institute
Japanese researchers conduct significant PSP research, including trials of tau aggregation inhibitors.
[CurePSP](https://curepsp.org) serves as the primary advocacy organization for PSP, CBD, and related disorders:
The [Tau Consortium](https://tauconsortium.org) funds research and clinical trials for tauopathies including PSP:
While focused on Parkinson's disease, the [Parkinson's Foundation](https://www.parkinson.org) provides resources for PSP patients and families:
Several therapeutic approaches target tau pathology in PSP.[@boxer2020][@hoglinger2021][@vandevrede2020][@williams2005]
Tau aggregation inhibitors: Drugs designed to prevent tau protein misfolding and aggregation. The TauRx LMTM program has evaluated this approach in PSP.
Anti-tau antibodies: Monoclonal antibodies targeting extracellular tau to prevent propagation. Several companies have developed anti-tau antibodies in clinical trials.[@boxer2020][@vandevrede2020][@wen2021]
Tau phosphorylation modulators: Drugs targeting kinases (e.g., GSK-3β, CDK5) or promoting phosphatases to reduce tau phosphorylation.[@hoglinger2021][@stamelou2022][@bjornsdottir2018][@williams2005]
Cell-based therapies: Stem cell approaches aim to replace damaged neurons or provide neurotrophic support.[@pascual2021]
Mitochondrial protectors: Drugs targeting mitochondrial dysfunction, a key feature of PSP pathology.[@hoglinger2021][@jabbari2020][@holmes2019][@roemer2018]
Anti-inflammatory agents: Microglia-modulating approaches aim to reduce neuroinflammation.[@holmes2019]
Biomarker-enriched enrollment and subtype stratification are increasingly used in modern PSP/CBS trials: tau PET and CSF signatures can improve cohort homogeneity, while neurofilament light chain and genotype-aware analyses (including MAPT haplotype context) may improve power in small populations.[@wen2021][@jabbari2020][@sanchez2019][@bjornsdottir2018][@schott2021][@stamelou2020]
Several device-based and non-pharmacological approaches are being investigated for CBS and PSP:
Transcranial Direct Current Stimulation (tDCS): Non-invasive brain stimulation that modulates cortical excitability. Current trials (NCT07291687) evaluate tDCS combined with motor training to improve motor function in neurodegenerative diseases.[@nctf]
Transcranial Magnetic Stimulation (TMS): Another non-invasive technique being studied in PSP (NCT04468932) for potential benefits on motor and cognitive symptoms.[@ncth]
Scrambler Therapy: A novel neuromodulation technique for chronic neuropathic pain. Being evaluated in CBS patients (NCT05653778) where pain is a significant symptom affecting quality of life.[@nctg]
Deep Brain Stimulation (DBS): While not currently in active trials for CBS/PSP, DBS has been explored for symptom management in related disorders.
NAD+ Replenishment Therapy: The NADAPT trial (NCT06162013) targets cellular energy metabolism, which is impaired in PSP, MSA, and CBS. This novel approach aims to improve mitochondrial function through NAD+ precursor supplementation.[@ncte]
Documenting failed trials is critical for understanding what approaches have been tried and why they did not work. Several PSP clinical trials have been terminated or completed without success:
UCB0107 Long-term Safety Study (NCT04658199): This study evaluated the long-term safety and tolerability of UCB0107, a tau-targeted antibody, in PSP patients who had previously participated in earlier-phase studies. While the extension study assessed safety, the original efficacy trials did not meet their primary endpoints.
Gosuranemab (BIIB092): This anti-tau antibody targeting extracellular tau oligomers was evaluated in PSP. The trial was terminated based on futility analysis — the antibody did not demonstrate sufficient efficacy to warrant continuation.
Tilavonemab (ABBV-8E12): Another anti-tau antibody targeting tau aggregates. The PSP trial was terminated after interim analysis suggested lack of efficacy.
NNIPPS Study (NCT00211224): Neuroprotection and Natural History in Parkinson's Plus Syndromes — this study was terminated. It had aimed to evaluate neuroprotective strategies in PSP and related disorders.
Understanding why these trials failed provides important mechanistic insights:
The informed consent process explains trial procedures, risks, and your rights. Take time to:
The following recruiting trials were identified through comprehensive searches of ClinicalTrials.gov for CBS, PSP, tauopathy, 4R-tauopathy, atypical parkinsonism, and related conditions. Target: 50+ trials.
Related Experiments:
From the [SciDEX Exchange](/exchange) — scored by multi-agent debate
Related Analyses: