FDDNP Protocol for Visualizing Brain Proteinopathies to Assist in the Diagnosis of Persons With Suspected CTE and AD
NCT ID: NCT04311281
Last Updated: 2021-05-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
OBSERVATIONAL
2021-05-31
2021-05-03
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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Suspected AD
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).
[F-18]FDDNP-PET
\[F-18\]FDDNP, or 2-(1-{6-\[(2-\[F-18\]fluoroethyl)(methyl)amino\]-2- naphthyl}ethylidene)malononitrile, is a positron emission tomography (PET) radiotracer developed for the in vivo visualization of tau and amyloid-beta (Aβ) deposition in the brain.
Suspected CTE / TES
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
[F-18]FDDNP-PET
\[F-18\]FDDNP, or 2-(1-{6-\[(2-\[F-18\]fluoroethyl)(methyl)amino\]-2- naphthyl}ethylidene)malononitrile, is a positron emission tomography (PET) radiotracer developed for the in vivo visualization of tau and amyloid-beta (Aβ) deposition in the brain.
Interventions
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[F-18]FDDNP-PET
\[F-18\]FDDNP, or 2-(1-{6-\[(2-\[F-18\]fluoroethyl)(methyl)amino\]-2- naphthyl}ethylidene)malononitrile, is a positron emission tomography (PET) radiotracer developed for the in vivo visualization of tau and amyloid-beta (Aβ) deposition in the brain.
Eligibility Criteria
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Inclusion Criteria
* Participant may be male or female and of any race/ethnicity
* Age 18 to 80 years at the time of study drug dosing
* Female participants must be either surgically sterilized or post-menopausal, defined as at least one-year without menses as reported by the participant or have a negative serum pregnancy test
* Participant or participant's legally acceptable representative (when appropriate) provides informed consent
* Participant is capable of complying with study procedures
* Participant is capable of communicating with study personnel
* Participant is willing to undergo longitudinal follow-up at 1 and 2 years after the Imaging Visit
* All participants will meet criteria for mild cognitive impairment (Petersen et al, 2014) or Mild Neurocognitive Disorder (APA, 2013):
* Patient awareness of a memory problem, preferably confirmed by another person who knows the patient
* Memory impairment detected with standard assessment tests
* Ability to perform normal daily activities
* For a broad definition of mild cognitive impairment, we also use guidelines to identify those with other mild cognitive impairment subtypes, including those with memory impairment and/or additional cognitive deficits (Winblad et al, 2004). The diagnosis will be corroborated by clinical judgment and include participants who score 1 standard deviation or more below the age-corrected norms because this threshold for impairment yields high sensitivity for predicting dementia (de Jager et al, 2005). To balance increased sensitivity with specificity, impairment on at least 2 neuropsychological tests will be required (Jak et al., 2009).
Participants with suspected CTE enrolling in the trial must meet all of the following criteria:
• Participant must meet the most recently proposed clinical criteria for suspected CTE (termed possible traumatic encephalopathy syndrome or TES; Reams et al, 2016). These proposed diagnostic criteria for possible TES include the following features:
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: including depression, anxiety, agitation, aggression, paranoid ideation, deterioration of interpersonal relationships, and suicidality
* Behavioral change: including violence, poor impulse control, socially inappropriate behavior, avolition, apathy, change in personality, and comorbid substance abuse
* Motor disturbance: including bradykinesia, tremor, rigidity, gait instability, dysarthria, dysphagia, and ataxia
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).
Exclusion Criteria
* Participant is pregnant or nursing
* Phone screen of Telephone Interview for Cognitive Status-modified (TICS-M) ≥ 33
* Participant unable to remain still for duration of imaging procedure or has an inability to tolerate neuropsychological, clinical, or PET scan studies (e.g., head tremor that may cause head motion artifact, uncontrollable psychosis, acute suicidality)
* Participant has prior history of stroke or other condition of the head or neck that, in the investigator's opinion, might affect circulation to the head or image interpretation
* Preexisting major neurologic or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer)
* Participant has a major psychiatric disorder such as mania or schizophrenia, which might interfere with completing study procedures (APA, 2013)
* Participant has a psychiatric disorder, such as anxiety or depression, severe enough to interfere with completing study procedures
* Participant has a condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete accurate quality data
* Participant has a history of significant prescription drug, non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin or derivatives
* Participant has previously received \[F-18\]FDDNP at any time, or any other investigational product within the past thirty days
* Participant has a history of allergic reactions to albumin
* Participant has severe anemia in which case the use of albumin would be medically contraindicated
* Participant has cardiac failure in which case the use of albumin would be contraindicated
* Participant has unstable cardiac disease or uncontrolled hypertension (systolic BP \> 170 or diastolic BP \> 100)
* Participants taking ibuprofen or naproxen will be asked to stop taking the medication for five days before the PET scan since these medicines may affect \[F-18\]FDDNP-PET scan results. Other anti-inflammatory medicines, such as diclofenac or aspirin, can be substituted during that period. If the participant cannot temporarily discontinue the medicine, that participant will be excluded from the study
* Participant has used of any investigational drugs within the previous month or has participated in imaging or other clinical research protocols that might confound study results
18 Years
80 Years
ALL
No
Sponsors
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University of California, Los Angeles
OTHER
Responsible Party
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Helen Lavretsky, MD
Principal Investigator
Principal Investigators
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Helen Lavretsky, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, Los Angeles, Semel Institute
References
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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Washington, DC: American Psychiatric Association, 2013.
Busse A, Hensel A, Guhne U, Angermeyer MC, Riedel-Heller SG. Mild cognitive impairment: long-term course of four clinical subtypes. Neurology. 2006 Dec 26;67(12):2176-85. doi: 10.1212/01.wnl.0000249117.23318.e1.
Csukly G, Siraly E, Fodor Z, Horvath A, Salacz P, Hidasi Z, Csibri E, Rudas G, Szabo A. The Differentiation of Amnestic Type MCI from the Non-Amnestic Types by Structural MRI. Front Aging Neurosci. 2016 Mar 30;8:52. doi: 10.3389/fnagi.2016.00052. eCollection 2016.
de Jager CA, Budge MM. Stability and predictability of the classification of mild cognitive impairment as assessed by episodic memory test performance over time. Neurocase. 2005 Feb;11(1):72-9. doi: 10.1080/13554790490896820.
Harrison J, Minassian SL, Jenkins L, Black RS, Koller M, Grundman M. A neuropsychological test battery for use in Alzheimer disease clinical trials. Arch Neurol. 2007 Sep;64(9):1323-9. doi: 10.1001/archneur.64.9.1323.
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012 Jan;8(1):1-13. doi: 10.1016/j.jalz.2011.10.007.
Jak AJ, Bondi MW, Delano-Wood L, Wierenga C, Corey-Bloom J, Salmon DP, Delis DC. Quantification of five neuropsychological approaches to defining mild cognitive impairment. Am J Geriatr Psychiatry. 2009 May;17(5):368-75. doi: 10.1097/JGP.0b013e31819431d5.
Monsell SE, Liu D, Weintraub S, Kukull WA. Comparing measures of decline to dementia in amnestic MCI subjects in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set. Int Psychogeriatr. 2012 Oct;24(10):1553-60. doi: 10.1017/S1041610212000452. Epub 2012 Apr 16.
Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014 Mar;275(3):214-28. doi: 10.1111/joim.12190.
Reams N, Eckner JT, Almeida AA, Aagesen AL, Giordani B, Paulson H, Lorincz MT, Kutcher JS. A Clinical Approach to the Diagnosis of Traumatic Encephalopathy Syndrome: A Review. JAMA Neurol. 2016 Jun 1;73(6):743-9. doi: 10.1001/jamaneurol.2015.5015.
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004 Sep;256(3):240-6. doi: 10.1111/j.1365-2796.2004.01380.x.
Other Identifiers
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18-001176
Identifier Type: -
Identifier Source: org_study_id
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