FDDNP Protocol for Visualizing Brain Proteinopathies to Assist in the Diagnosis of Persons With Suspected CTE and AD

Withdrawn

• Conditions: Suspected Chronic Traumatic Encephalopathy (CTE) or Traumatic Encephalopathy Syndrome (TES); Suspected Alzheimer's Disease (AD)
• Interventions: Biological: [F-18]FDDNP-PET

• Registration Number: NCT04311281
• Lead Sponsor: University of California, Los Angeles

Brief Summary

The primary objective of this study is to demonstrate the safety and efficacy of positron emission tomography (PET) imaging with a radioactive compound called \[F-18\]FDDNP in subjects with suspected Alzheimer's disease or suspected chronic traumatic encephalopathy (CTE) to predict clinical decline after one and two years.

Detailed Description

The investigators will enroll approximately 180 participants with mild cognitive impairment (90 with suspected Alzheimer's Disease and 90 with suspected Chronic Traumatic Encephalopathy with a history of head trauma).

Participants will come to UCLA for 4 visits and will be called twice. The study duration is 2 years.

Participants will first complete an over the phone screening to assess their eligibility. If they pass the phone screen, then they will be invited to complete an in-person screen and will sign the informed consent form. They will then undergo a neurological evaluation, blood draw, and neuropsychological testing.

Within a month of the screening visit, participants will complete the imaging visit. Participants will undergo a magnetic resonance imaging (MRI) scan, if eligible, and a PET scan with FDDNP. For participants who are unable to undergo an MRI due to contraindications, they will complete a CT scan.

Participants will be monitored for possible adverse events following the procedures and will be called 24 hours later and 2 weeks later to assess for any potential adverse events.

At the one and two-year follow-up visits, participants' medical history will be reviewed. At this time, they will also complete a neuropsychiatric evaluation, blood draw and neuropsychological testing.

Prediction of clinical and cognitive decline from \[F-18\] FDDNP PET scan readers (blinded to clinical evaluations) and clinicians (blinded to \[F-18\]FDDNP PET scan results) will be compared with actual clinical outcomes determined at one and two-year follow-up visits.

Study Timeline

• Study First Submitted: 2020-03-12
• Study First Submitted QC: 2020-03-12
• Study First Posted: 2020-03-17
• Status Verified: 2021-05
• Study Start: 2021-05
• Primary Completion: 2021-05-03
• Study Completion: 2021-05-03
• Last Update Submitted: 2021-05-03
• Last Update Posted: 2021-05-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Suspected AD	[F-18]FDDNP-PET	Participants with suspected AD enrolling in the trial must meet all of the following criteria: * Cognitive deficits do not occur exclusively in the context of a delirium. * Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia). * There is insidious onset and gradual progression of impairment in one or more cognitive domains. * The participant has documented memory problems in one or more other cognitive domains, such as language, visual-spatial functioning, executive functioning, etc. (Busse et al., 2006).
Suspected CTE / TES	[F-18]FDDNP-PET	Required Features: * Persistence of symptoms for longer than 2 years; no other neurologic disorder that is more likely to account for all the clinical features; history of head trauma exposure; progressive course; and at least 1 supportive feature * History of head trauma exposure, typically associated with history of concussion, although may be limited to subconcussive trauma * Head trauma exposure is repetitive in nature * Demonstrated progressive course * Delayed symptom onset * Self-report or observer report of cognitive dysfunction, confirmed with objective cognitive decline documented by results of formal neuropsychological testing. Cognitive decline typically affects more than 1 domain (executive, visuospatial, memory, and language). Supportive Features (only 1 required): * Emotional dysregulation * Behavioral change * Motor disturbance

Primary Outcome Measures

Name	Time	Method
Clinical Dementia Rating Sum of Box Scores (CDR-SB)	2 years	We propose to use the CDR Sum of Box Scores (CDR-SB) as the primary efficacy endpoint to be predicted (at two-year follow-up) following baseline when the \[F-18\]FDDNP-PET imaging is performed. The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18. We will use change in CDR-SB score as the common outcome variable. We will convert individual CDR-SB scores into standardized scores by subtracting the baseline mean and dividing by the baseline standard deviation of the study sample (Monsell et al, 2012). Individuals experiencing worsening of cognition by at least 0.5 standard deviation per year in the standardized CDR-SB score will be classified as cognitive decliners; others will be classified as cognitive maintainers.

Secondary Outcome Measures

Name	Time	Method
Change in Executive Functioning Domain Score	2 years	Calculated as the average of z- transformed scores of: Trails B-A, Category Fluency, Letter Fluency, and Wechsler Adult Intelligence Scale-IV Digit Symbol and Digit Span backwards (Harrison et al., 2007).
Conversion to Dementia	2 years	For a dementia diagnosis, we will use major neurocognitive disorder according to the Diagnostic and Statistical Manual-5 \[DSM-5\] criteria (APA, 2013; Csukly et al, 2016).