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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 45 Years and older
- Sex
- All sexes
- Healthy volunteers
- Accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests whether a brain scan called F-18 FNT-PET can predict worsening memory and thinking problems and whether the scan drug is safe. It is for people with mild cognitive impairment linked to suspected Alzheimer's disease or CTE, a brain condition linked to repeated head injuries. Part A also includes healthy volunteers.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have mild memory and thinking problems linked to suspected CTE and be older than 45, or linked to suspected Alzheimer's and be older than 50. A required rating of memory and daily skills must be 0.5.
- Have a study partner who sees you often, about more than 3–4 times a week, attends all clinic visits, and helps with study tasks.
- You or your legal representative, plus your study partner, must give consent. Be willing to follow study steps, talk with staff, and attend 1-year and 2-year follow-up visits for Part B.
- Women with memory and thinking problems must have had surgery to prevent pregnancy, have gone at least 1 year without periods, or have a negative blood pregnancy test.
- For suspected CTE: have repeated head injuries, delayed symptoms lasting more than 2 years, worsening thinking confirmed by tests, and at least one change in emotions, behavior, or movement. No other nerve or brain disorder can better explain all symptoms.
- For suspected Alzheimer's: meet diagnosis rules, have slowly worsening memory for at least 1 year, and meet required blood and thinking test results. Thinking problems cannot be explained better by another illness or happen only during sudden confusion.
- For suspected Alzheimer's: take stable doses of the listed memory medicines for at least 4 months and expect to keep them stable. You may also qualify if these drugs are unsafe for you or failed before and you expect to stay off them.
- Healthy volunteers in Part A must be within 3 years of a Part A patient's age, have no important health or thinking problems, and score at least 27 on a thinking test. No parent, sibling, or child may have had Alzheimer's or another brain disease that worsens over time before age 65.
Who can't join
- Are pregnant or breastfeeding, cannot stay still for scans, or cannot complete study tests. A health condition or personal situation that prevents complete, reliable study results may also rule you out.
- Had a stroke, mini-stroke, seizure, or certain head or neck conditions in the past 12 months that could affect scans. Major illnesses, mental health conditions that interfere with study tasks, or unrelated brain scan findings may also rule you out.
- Have a history of significant misuse of alcohol, prescription medicines, or other drugs.
- Have an albumin allergy, or severe low red blood cells or heart failure that makes albumin unsafe. Unstable heart disease or blood pressure above 170 systolic or 100 diastolic also rules you out.
- Use benzodiazepines, medicines often used for anxiety or sleep, within 24 hours before study visits, or plan to take ibuprofen or naproxen within 5 days before the PET scan.
- Previously received F-18 FNT, recently received other study drugs or radioactive scans or drugs, or joined research that could affect the results. Waiting periods depend on the drug or study.
- Have implants not cleared for MRI, fear of enclosed spaces during MRI, or another reason you cannot safely have an MRI.
- Received monoclonal antibody treatment within 180 days before screening, or plan to receive aducanumab, lecanemab, or other potentially approved early Alzheimer's treatments during the study.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: Participants with MCI enrolling in the trial must meet all the following 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: a. All of the following features are required: i) 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 ii) History of head trauma exposure, typically associated with history of concussion, although may be limited to subconcussive trauma iii) Head trauma exposure is repetitive in nature iv) Demonstrated progressive course v) Delayed symptom onset vi) 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 (neuropsychological tests, visuospatial, memory, and language) b. Only 1 of the following supportive features is required: i) Emotional dysregulation: including depression, anxiety, agitation, aggression, paranoid ideation, deterioration of interpersonal relationships, or suicidality ii) Behavioral change: including violence, poor impulse control, socially inappropriate behavior, avolition, apathy, change in personality, or comorbid substance abuse iii) Motor disturbance: including bradykinesia, tremor, rigidity, gait instability, dysarthria, dysphagia, or ataxia 9. Participants with MCI due to suspected AD must meet 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. Inclusion Criteria for Healthy Volunteers (Part A): 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. Exclusion Criteria: 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.
Study sites (1)
IL
- Endeavor Health Systems · Evanston, IL 60201Rosa M Vazquez · Study contact · 8475034333 · rvazquez@northshore.orgChad Yucus, MD · Principal investigatorMore trials in Evanston