Using neuroimaging to improve diagnosis and prognosis of Parkinson's disease and related conditions

Quantitative Diagnostics of Parkinsonian Syndromes Using Multi-modal Neuroimaging and Deep Learning

This study is trying to find brain imaging markers that can help doctors better diagnose and predict how Parkinson's disease and similar conditions will progress in patients.

Quick facts

• Study type: Observational
• Enrollment: 90 (estimated)
• Sex: All
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT03872102 on ClinicalTrials.gov

What this trial studies

This observational study aims to identify neuroimaging biomarkers that can predict the progression rate of Parkinson's disease (PD) and differentiate it from atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Over a two-year period, participants will undergo various neuroimaging techniques, and their clinical data will be analyzed using machine learning methods. The study will involve both existing PD patients with historical data and newly recruited patients who will be monitored clinically and through imaging. The goal is to fill critical gaps in the management of parkinsonian symptoms by developing clinically accepted biomarkers.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with Parkinson's disease, multiple system atrophy, or progressive supranuclear palsy, particularly those within specific timeframes since diagnosis.

Not a fit: Patients with atypical parkinsonian syndromes who do not meet the study's inclusion criteria or those who are unable to participate in imaging studies may not benefit.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnostic accuracy and personalized treatment plans for patients with Parkinson's disease and related disorders.

How similar studies have performed: Other studies have shown promise in using neuroimaging for similar purposes, but this approach aims to develop novel biomarkers specifically for PD and its variants.

Eligibility criteria

Inclusion Criteria:

For Aim 1:

* Diagnosis of Parkinson disease
* Existence of sufficient clinical data from previous UTS Southwestern longitudinal study to determine progression rate (categorized as fast or slow)
* Availability of suitable matched participant in the alternate progression group (fast or slow)
* Willingness to participate in the imaging studies required for this study and to provide written informed consent

For Aim 2:

PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for PD.

* Duration of PD (since diagnosis) is \< 5 years
* Willing to participate in imaging and clinical scoring visits, and provide written informed consent
* Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move)

MSA subjects will be recruited in accordance with the Second Consensus Statement on Diagnosis of Multiple System Atrophy.

* Duration of MSA (since diagnosis) is \< 5 years
* Willing to participate in imaging and clinical scoring visits, and provide written informed consent
* Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move away during the study)

PSP subjects will be recruited in accordance with the MDS Criteria for Diagnosis of Progressive Supranuclear Palsy and must meet the designation of "probable PSP" for inclusion.

* Willing to participate in imaging and clinical scoring visits, and provide written informed consent
* Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move away during the study)

Control subjects will be recruited who meet the following criteria:

* Roughly age and sex matched with the subjects in the PD cohort
* No history or examination findings suggestive of any neurodegenerative disease
* Normal gait, balance, and eye movements for age
* No clinical evidence for symptomatic orthostatic hypotension
* Willing to participate in imaging and clinical scoring visits, and provide written informed consent
* Subject and investigator agree that it is highly likely subject will be able to participate throughout the 2-year study period (no plans to move away during the study)

Exclusion Criteria:

For Aims 1 and 2:

* Any contraindications to undergoing the multimodal imaging program
* All females of child-bearing potential, between the ages of 18-55, will be excluded from the study, unless they are confirmed to be not pregnant with a pregnancy test prior to scanning
* This study will require constant clear communication throughout the duration of the study; therefore, non-English speakers will be excluded
* Right-handed finger amputees
* Cast on right hand or fingers at the time of enrollment
* Has clinically significant liver, kidney, lung, metabolic or hormone disturbances which pose safety risk
* Has a current clinically significant heart disease that poses a safety risk
* Has a current clinically significant infectious disease or a medical comorbidity which poses a safety risk
* Has a history of relevant severe drug allergy or hypersensitivity
* Have a history of drug, alcohol, or substance dependence or abuse within the last year, or prior prolonged history of dependence or abuse
* Currently undergoing chemotherapy or radiation for cancer
* Recreational drug use in past six months
* Central nervous systems disease or brain injury that would preclude participation in this study
* Psychiatric or neurological disorder that would preclude participation in this study
* Inability to keep or maintain research appointments

For Aim 1:

* Severe disease progression such that participation in the imaging tests would be impossible or difficult
* Non-availability of a suitable matched participant in the alternate progression group (fast or slow)

For Aim 2:

PD subjects

1. Unequivocal cerebellar abnormalities
2. Downward vertical gaze limitation or slowing of downward saccades
3. Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
4. Parkinsonian features restricted to the lower limbs for \> 3 years
5. Treatment with dopamine blockers or depleters in a time course consistent with drug induced parkinsonism
6. Absence of an observable response to high dose levodopa despite moderate disease severity
7. Expert considers a diagnosis of alternative syndrome more likely than PD
8. Rapid progression of gait impairment requiring wheelchair within 5 years of onset
9. Complete absence of progression of motor symptoms over 5 years unless due to treatment
10. Early bulbar dysfunction within the first 5 years since diagnosis
11. Inspiratory respiratory dysfunction (stridor or frequent sighs)
12. Severe autonomic failure in the first 5 years
13. Recurrent falls (\>1 per year) because of impaired balance in the first 3 years
14. Disproportionate dystonic anterocollis or hand contractures of hands or feet within 10 years
15. Absence of any of the common non-motor features of PD despite 5 years of disease
16. Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor toe signs)
17. Bilateral symmetric parkinsonism

MSA subjects

1. Clinically significant neuropathy
2. Hallucinations not induced by drugs
3. Onset after age 75 years
4. Family history of ataxia or parkinsonism
5. White matter lesions suggesting multiple sclerosis

PSP subjects

1. Predominant, otherwise unexplained impairment of episodic memory, suggestive of AD (Alzheimer's disease)
2. Predominant, otherwise unexplained autonomic failure, e.g., orthostatic hypotension (orthostatic reduction in blood pressure after 3 minutes standing \> 30 mm Hg systolic or \> 15 mm Hg diastolic), suggestive of multiple system atrophy or Lewy body disease
3. Predominant, otherwise unexplained visual hallucinations or fluctuations in alertness, suggestive of dementia with Lewy bodies
4. Predominant, otherwise unexplained multisegmental upper and lower motor neuron signs, suggestive of motor neuron disease (pure upper motor neuron signs are not an exclusion criterion)
5. Sudden onset or step-wise or rapid progression of symptoms, in conjunction with corresponding imaging or laboratory findings, suggestive of vascular etiology, autoimmune encephalitis, metabolic encephalopathies, or prion disease
6. History of encephalitis
7. Prominent appendicular ataxia
8. Identifiable cause of postural instability, e.g., primary sensory deficit, vestibular dysfunction, severe spasticity, or lower motor neuron syndrome

Control subjects

a. In the investigator's opinion, an unsuitable candidate to serve as a control

Where this trial is running

Dallas, Texas

• UT Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Padraig E O'Suilleabhain, MD — University of Texas Southwestern Medical Center
• Study coordinator: Padraig E O'Suilleabhain, MD

Conditions Parkinson Disease; Multiple System Atrophy; Progressive Supranuclear Palsy