RECRUITING

Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease

Conditions

Alzheimer Disease Chronic Traumatic Encephalopathy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

CMK-0301 is a multi-site, randomized clinical trial to evaluate the safety and efficacy of \[F-18\]Flornaptitril-PET (F-18 FNT-PET) for the prediction of clinical progression of Mild Cognitive Impairment (MCI) with either Suspected Chronic Traumatic Encephalopathy (CTE) or Alzheimer's Disease (AD). The primary objectives of the study are to: (1) To determine the accuracy of F-18 FNT-PET in prediction of clinical decline and (2) To assess the safety and tolerability of F-18 FNT. The secondary objectives include: (1) To demonstrate the feasibility of F-18 FNT-PET in differentiation of participants with suspected chronic traumatic encephalopathy (CTE) from those with suspected Alzheimer's disease (AD) by trained image readers, (2) To evaluate disease progression in participants with suspected CTE or AD and (3) To evaluate the correlation between F-18 FNT-PET regional and summary visual reads scan and other assessments.

Official Title

Visualizing Brain Proteinopathies Using [F-18]Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment With Either Suspected Chronic Traumatic Encephalopathy or Alzheimer's Disease

Quick Facts

Study Start:2025-07-01

Study Completion:2029-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06254469

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:45 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Diagnosis of MCI due to suspected CTE, and with age \>45 years, or AD, and with age \>50 years at the time of the Screening Visit (see Inclusion Criteria 9) 2. Participants must have a trial partner who has frequent interaction with them (approximately \>3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures 3. Participants, or in the Investigator's opinion, participant's legally acceptable representative, and a trial partner provide informed consent as required by IRB 4. Female participants must be either surgically sterilized or post-menopausal, defined as at least 1 year without menses as reported by the participant or have a negative serum pregnancy test 5. Willing to comply with trial procedures 6. Willing to communicate with trial personnel 7. Willing to undergo longitudinal follow-up visits at 1 and 2 years after the Imaging Visit (only for Part B) 8. CDR global score of 0.5 9. Participants with MCI due to suspected CTE must meet the diagnostic standards of possible traumatic encephalopathy syndrome as all the following criteria: 1. Diagnosis of MCI due to suspected AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA) 2. Documented evidence of memory decline with gradual onset and slow progression for at least 1 year. If medically documented evidence is not available, an informant may provide confirmatory evidence 3. An MMSE-2 score of 22 to 30, inclusive, at the Screening Visit 4. Biomarker positive based on predefined plasma p-tau cutoff 5. Modified Hachinski Ischemic Score of ˂4 at the Screening Visit 6. Cognitive deficits do not occur exclusively in the context of delirium 7. Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia), or other medical condition (e.g., hypothyroidism) 8. Treated with a stable dosage regimen of acetylcholinesterase inhibitors (AchEI) and/or memantine for at least 4 months prior to the Screening Visit. Participants should be expected to remain on a stable dosage regimen of these medications for the duration of the trial. Participants who are not being treated with AchEI and/or memantine at the time of the Screening Visit due to contraindications or previous failed treatment with these medications are also eligible for inclusion, if it is expected that participants will not be treated with these medications for the duration of the trial. 1. Medically healthy, at the age within 3 years of any participants with MCI due to suspected CTE or AD in Part A, and with no clinically relevant findings on physical examination or laboratory results 2. Participants must have a trial partner who has frequent interaction with them (approximately \>3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures 3. No cognitive impairment based upon cognitive assessment and as evaluated by the Investigator 4. No first-degree family history of early-onset AD or other neurodegenerative diseases (prior to age 65) 5. An MMSE-2 score ≥27.	1. Pregnant or breastfeeding 2. Unable to remain still for duration of imaging procedure or have an inability to tolerate neuropsychological, clinical, or PET scan studies (e.g., head tremor that may cause head motion artifact, uncontrollable psychosis, acute suicidality) 3. History of stroke, transient ischemic attack, seizures, or other condition of the head or neck within 12 months prior to the Screening Visit that, in the Investigator's opinion, might affect circulation to the head or image interpretation 4. Preexisting major neurologic or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer) 5. Psychiatric disorder such as mania, schizophrenia, anxiety, or depression (Geriatric Depression Scale ≥10), which in the Investigator's opinion, might interfere with completing trial procedures 6. Condition or personal circumstance that, in the Investigator's opinion, might interfere with the collection of complete, good quality data 7. History of significant prescription drug, non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin, or derivatives 8. Previously received F-18 FNT at any time, or any other investigational product (IP) within the past 30 days 9. History of allergic reactions to albumin, or severe anemia or cardiac failure in which case the use of albumin would be medically contraindicated 10. Unstable cardiac disease or uncontrolled hypertension (systolic blood pressure \[BP\] \>170 mmHg or diastolic BP \>100 mmHg) 11. Any use of benzodiazepines within 24 hours prior to all trial visits 12. Plan to take ibuprofen or naproxen within 5 days before the PET scan 13. Received any radioactive drugs or scans within the previous month or 10 half-lives of the drug, whichever is longer, or participated in imaging or other clinical research studies that might confound trial results 14. Implants (e.g., implanted cardiac pacemakers or defibrillators, insulin pumps, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips, or other medical implants that have not been certified for MRI), a history of claustrophobia in MRI, or any contraindication for MRI 15. History of any CT/MRI finding such as mass lesions or brain infection that are unrelated to the trial 16. Participated in another clinical trial for an investigational agent (other than monoclonal antibody) and taken at least one dose of trial drug, unless confirmed as placebo, within 90 days prior to the Screening Visit. The end of a previous investigational trial is defined as the date of the last dose of trial drug 17. Monoclonal antibody treatment within the previous 180 days prior to the Screening Visit 18. Plan to receive treatment of aducanumab, lecanemab, or other potentially approved treatment options for Early AD during the trial.

Inclusion Criteria

Exclusion Criteria

1. Diagnosis of MCI due to suspected CTE, and with age \>45 years, or AD, and with age \>50 years at the time of the Screening Visit (see Inclusion Criteria 9) 2. Participants must have a trial partner who has frequent interaction with them (approximately \>3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures 3. Participants, or in the Investigator's opinion, participant's legally acceptable representative, and a trial partner provide informed consent as required by IRB 4. Female participants must be either surgically sterilized or post-menopausal, defined as at least 1 year without menses as reported by the participant or have a negative serum pregnancy test 5. Willing to comply with trial procedures 6. Willing to communicate with trial personnel 7. Willing to undergo longitudinal follow-up visits at 1 and 2 years after the Imaging Visit (only for Part B) 8. CDR global score of 0.5 9. Participants with MCI due to suspected CTE must meet the diagnostic standards of possible traumatic encephalopathy syndrome as all the following criteria:
1. Diagnosis of MCI due to suspected AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA)
2. Documented evidence of memory decline with gradual onset and slow progression for at least 1 year. If medically documented evidence is not available, an informant may provide confirmatory evidence
3. An MMSE-2 score of 22 to 30, inclusive, at the Screening Visit
4. Biomarker positive based on predefined plasma p-tau cutoff
5. Modified Hachinski Ischemic Score of ˂4 at the Screening Visit
6. Cognitive deficits do not occur exclusively in the context of delirium
7. Cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia), or other medical condition (e.g., hypothyroidism)
8. Treated with a stable dosage regimen of acetylcholinesterase inhibitors (AchEI) and/or memantine for at least 4 months prior to the Screening Visit. Participants should be expected to remain on a stable dosage regimen of these medications for the duration of the trial. Participants who are not being treated with AchEI and/or memantine at the time of the Screening Visit due to contraindications or previous failed treatment with these medications are also eligible for inclusion, if it is expected that participants will not be treated with these medications for the duration of the trial.
1. Medically healthy, at the age within 3 years of any participants with MCI due to suspected CTE or AD in Part A, and with no clinically relevant findings on physical examination or laboratory results
2. Participants must have a trial partner who has frequent interaction with them (approximately \>3-4 times per week), will be present for all clinic visits, and can assist in compliance with trial procedures
3. No cognitive impairment based upon cognitive assessment and as evaluated by the Investigator
4. No first-degree family history of early-onset AD or other neurodegenerative diseases (prior to age 65)
5. An MMSE-2 score ≥27.

1. Pregnant or breastfeeding
2. Unable to remain still for duration of imaging procedure or have an inability to tolerate neuropsychological, clinical, or PET scan studies (e.g., head tremor that may cause head motion artifact, uncontrollable psychosis, acute suicidality)
3. History of stroke, transient ischemic attack, seizures, or other condition of the head or neck within 12 months prior to the Screening Visit that, in the Investigator's opinion, might affect circulation to the head or image interpretation
4. Preexisting major neurologic or other physical illness that could confound results (e.g., multiple sclerosis, diabetes, cancer)
5. Psychiatric disorder such as mania, schizophrenia, anxiety, or depression (Geriatric Depression Scale ≥10), which in the Investigator's opinion, might interfere with completing trial procedures
6. Condition or personal circumstance that, in the Investigator's opinion, might interfere with the collection of complete, good quality data
7. History of significant prescription drug, non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin, or derivatives
8. Previously received F-18 FNT at any time, or any other investigational product (IP) within the past 30 days
9. History of allergic reactions to albumin, or severe anemia or cardiac failure in which case the use of albumin would be medically contraindicated
10. Unstable cardiac disease or uncontrolled hypertension (systolic blood pressure \[BP\] \>170 mmHg or diastolic BP \>100 mmHg)
11. Any use of benzodiazepines within 24 hours prior to all trial visits
12. Plan to take ibuprofen or naproxen within 5 days before the PET scan
13. Received any radioactive drugs or scans within the previous month or 10 half-lives of the drug, whichever is longer, or participated in imaging or other clinical research studies that might confound trial results
14. Implants (e.g., implanted cardiac pacemakers or defibrillators, insulin pumps, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips, or other medical implants that have not been certified for MRI), a history of claustrophobia in MRI, or any contraindication for MRI
15. History of any CT/MRI finding such as mass lesions or brain infection that are unrelated to the trial
16. Participated in another clinical trial for an investigational agent (other than monoclonal antibody) and taken at least one dose of trial drug, unless confirmed as placebo, within 90 days prior to the Screening Visit. The end of a previous investigational trial is defined as the date of the last dose of trial drug
17. Monoclonal antibody treatment within the previous 180 days prior to the Screening Visit
18. Plan to receive treatment of aducanumab, lecanemab, or other potentially approved treatment options for Early AD during the trial.

Contacts and Locations

Study Contact

Henry M Chilton, PharmD

CONTACT

8654069859

hmchilton@ceremarkpharma.com

Principal Investigator

Chad Yucus, MD

PRINCIPAL_INVESTIGATOR

Endeavor Health System

Study Locations (Sites)

Endeavor Health Systems

Evanston, Illinois, 60201

United States

Collaborators and Investigators

Sponsor: CereMark Pharma, LLC

Chad Yucus, MD, PRINCIPAL_INVESTIGATOR, Endeavor Health System

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-01

Study Completion Date2029-06-30

Study Record Updates

Study Start Date2025-07-01

Study Completion Date2029-06-30

Terms related to this study

Additional Relevant MeSH Terms

Alzheimer Disease
Chronic Traumatic Encephalopathy