神経変性脳疾患におけるシクロオキシゲナーゼの PET イメージング
第 1 相試験: 神経変性脳疾患におけるシクロオキシゲナーゼの PET イメージング
Background:
About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation.
Objective:
To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers.
Eligibility:
Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181.
Design:
Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured.
Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs.
Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan.
Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.
調査の概要
詳細な説明
Study Description:
This pilot/exploratory study will examine whether cyclooxygenase 1 (COX-1) and COX-2 are elevated in the brain of individuals with neurodegenerative brain disease compared to healthy volunteers.
Objectives:
Primary Objective: To determine whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers.
Secondary Objective:
1) To determine retest variability and reliability for each radioligand. 2) To evaluate the specific binding of [11C]PS13 to COX-1 in healthy subjects through blocking study using Ketoprofen, a COX-1 inhibitor
Endpoints:
Primary Endpoint: Measurement of COX-1 and COX-2 density in brain after PET scans with [11C]PS13 and [11C]MC1, respectively.
Secondary endpoint: 1) To measure whole-brain distribution volume (VT) of COX-1 and COX-2 in a retest setting; 2) To correlate VT with the presence of amyloid in Alzheimer s disease (AD) patients, mild cognitive impairment (MCI) patients and healthy volunteers (HV); 3) To calculate the specific binding of [11C]PS13 with a Lassen plot
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前:Robert B Innis, M.D.
- 電話番号:(301) 594-1368
- メール:robert.innis@nih.gov
研究連絡先のバックアップ
- 名前:Tara N Turon, C.R.N.P.
- 電話番号:(301) 827-6599
- メール:tara.turon@nih.gov
研究場所
-
-
Maryland
-
Bethesda、Maryland、アメリカ、20892
- 募集
- National Institutes of Health Clinical Center
-
コンタクト:
- For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
- 電話番号:TTY8664111010 800-411-1222
- メール:prpl@cc.nih.gov
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
- INCLUSION CRITERIA:
Patients: In order to be eligible to participate in this study, patients must meet all of the following criteria:
- Aged 18 or older.
- 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.
- 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.
- Be in good general health as evidenced by medical history and physical examination.
- 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.
- 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:
- Aged 18 or older.
- Female participants of childbearing potential must be using a medically acceptable means of contraception
- Able provide informed consent.
- Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
- 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
- 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.
- 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:
- 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
- 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.
- Contraindications to ketoprofen, such as hypersensitivity to ketoprofen or history of upper or lower gastrointestinal bleeding.
- 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.
- Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
- Are unable to travel to the NIH.
- 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.
- 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.
- 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.
- Participants should not be under treatment with Aduhelm, nor should they have been treated in the past.
- 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).
- Pregnancy
- HIV infection
- Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:診断
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
他の:Only one arm
All subjects receive the same tests |
Injected IV followed by PET scanning Injected IV followed by PET scanning Injected IV followed by PET scanning |
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Measure the concentration of radioligands
時間枠:1-2 days
|
Density of COX-1 and COX-2 in brain |
1-2 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Measure the retest variability and reliability of the radioligans
時間枠:1-2 days
|
Density of COX-1 and COX-2 in brain |
1-2 days
|
協力者と研究者
捜査官
- 主任研究者:Robert B Innis, M.D.、National Institute of Mental Health (NIMH)
出版物と役立つリンク
一般刊行物
- Parcon P, Scrabis M, Norgaard M, Galassi A, Zanotti-Fregonara P, Liow JS, Innis RB, Kim MJ. [11C]PS13 PET shows that age is positively correlated with constitutively expressed cyclooxygenase-1 in the brain. J Cereb Blood Flow Metab. 2026 May 5:271678X261444895. doi: 10.1177/0271678X261444895. Online ahead of print.
- Ghazanfari N, Liow JS, Kim MJ, Cureton R, Lee A, Knoer C, Jenkins M, Hong J, Santamaria JAM, Shetty HU, Galassi A, Wighton P, Norgaard M, Greve DN, Zoghbi SS, Pike VW, Innis RB, Zanotti-Fregonara P. [11C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain. J Nucl Med. 2025 Jan 3;66(1):117-122. doi: 10.2967/jnumed.124.267928.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 200082
- 20-M-0082
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
results will be shared
IPD 共有時間枠
18 months after closure of protocol to Clincialtrials.gov
IPD 共有アクセス基準
BTRIS
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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