Imaging brain inflammation in neurodegenerative diseases

Phase 1 Study: PET Imaging of Cyclooxygenases in Neurodegenerative Brain Disease

This study is testing how levels of certain proteins in the brain relate to neurodegenerative diseases like Alzheimer's and Parkinson's by comparing them in patients and healthy volunteers using brain scans.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 184 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: radiation, methotrexate
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT04396873 on ClinicalTrials.gov

What this trial studies

This pilot study aims to investigate the levels of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in the brains of individuals diagnosed with neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, compared to healthy volunteers. Participants will undergo a series of screenings, including medical history, physical exams, and neuropsychological testing, followed by MRI scans and PET imaging using specific radioligands. The primary goal is to measure the density of COX-1 and COX-2 in the brain, while secondary objectives include assessing the reliability of the imaging techniques and correlating findings with amyloid presence in Alzheimer's patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with adult-onset neurodegenerative conditions like Alzheimer's disease, Parkinson's disease, or mild cognitive impairment.

Not a fit: Patients with non-neurodegenerative conditions or those under 18 years old may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved methods for diagnosing and monitoring neurodegenerative diseases through better understanding of brain inflammation.

How similar studies have performed: Previous studies have shown promise in using PET imaging to assess inflammation in neurodegenerative diseases, suggesting this approach may yield valuable insights.

Eligibility criteria

* INCLUSION CRITERIA:

Patients: In order to be eligible to participate in this study, patients must meet all of the following criteria:

1. Aged 18 or older.
2. Be able (or have their Legally Authorized Representative (LAR) be able) to understand the study and be willing to sign a written informed consent document.
3. Have been diagnosed by a neurologist or psychiatrist with MCI, ALS, PD, or an adult onset neurodegenerative dementia, such as AD (including amyloid negative subjects), FTD, corticobasal syndrome, or Huntington s disease.
4. Be in good general health as evidenced by medical history and physical examination.
5. Have their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
6. Agree to adhere to the lifestyle considerations.

Healthy volunteers: In order to be eligible to participate in this study, healthy volunteer subjects must meet all of the following criteria:

1. Aged 18 or older.
2. Female participants of childbearing potential must be using a medically acceptable means of contraception
3. Able provide informed consent.
4. Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
5. Be enrolled in 01-M-0254, The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17-M-0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies
6. Have their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
7. Agree to adhere to the lifestyle considerations.

EXCLUSION CRITERIA:

Both patients and healthy volunteers who meet any of the following criteria will be excluded from participation in this study:

1. Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). Any lab value that is two-times the upper limit or even lower values in the investigator s judgment. Creatinine level \>1.3 mg/dL
2. Subjects should not have taken Non-Steroidal Anti-Inflammatory Drugs (NSAID) for two weeks prior to the PET scan. Aspirin, corticosteroids (with the exception of skin products), or immunosuppressants (e.g., methotrexate) must not have been taken in the prior month.
3. Contraindications to ketoprofen, such as hypersensitivity to ketoprofen or history of upper or lower gastrointestinal bleeding.
4. Have other major neurological or medical diseases that may cause cognitive dysfunction, such as structural brain diseases, metabolic diseases, paraneoplastic syndromes, infectious diseases, or other significant neurological abnormalities.
5. Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
6. Are unable to travel to the NIH.
7. Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.
8. Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the patient and/or caregiver during the screening visit.
9. Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function of daily life.
10. Participants should not be under treatment with Aduhelm, nor should they have been treated in the past.
11. Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye).
12. Pregnancy
13. HIV infection
14. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Robert B Innis, M.D. — National Institute of Mental Health (NIMH)
• Study coordinator: Tara N Turon, C.R.N.P.

Conditions Parkinson's Disease; Dementia; Alzheimer's Disease; ALS; Mild Cognitive Impairment; PET Imaging; PD; Inflammation