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Imaging Dopamine D2 Agonist Binding Sites in Schizophrenia

2020年5月27日 更新者:NYU Langone Health
The goals of this study is to determine (1) if differences in D2/3 receptor affinity states exist between medication-free subjects with SCH (MF-S) compared with healthy controls (HC), (2) the degree to which pre- and post-synaptic factors contribute to increased striatal dopamine (DA) signaling in MF-S and (3) to test the hypotheses that optimal DA transmission in the dorsal caudate (DCA) is necessary for normal working memory (WM) function.

調査の概要

詳細な説明

An antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially, in a counterbalanced design, to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 MF-S and 30 HC. The main outcome measures will be baseline BPND and the percent change in BPND induced by amphetamine, denoted ∆BPND, in the subdivisions of the striatum. In addition, all subjects will undergo fMRI while performing a WM task concurrent with both the initial pre- and initial post-amphetamine PET scans to explore the relationship between DCA DA transmission and fMRI BOLD response in the dorsal lateral prefrontal cortex (DLPFC) during a WM task.

研究の種類

観察的

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

    • New York
      • New York、New York、アメリカ、10016
        • NYU Langone Health

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年~35年 (大人)

健康ボランティアの受け入れ

はい

受講資格のある性別

女性

サンプリング方法

非確率サンプル

調査対象母集団

SCHIZOPHRENIA patiens 18-35; Healthy Controls 18-35

説明

Inclusion Criteria:

  • HEALTHY CONTROLS

    1. Males or females between 18 and 35 years old (History)
    2. Absence of current (i.e. last six months) psychiatric conditions (including alcohol and drug abuse). Subjects with a history of a non-psychotic psychiatric disorder who have been asymptomatic and not taking medication for the past 6 months may be eligible.

      (History, SCID-NP (non-patient version))

    3. A negative urine toxicology with the exception of cannabis; in the case of a positive urine cannabis test a salivary cannabis test will be administered on the day of the PET scans to ensure subjects have not used within 24 - 48 hours.

      (Urine toxicology)

    4. Medically Healthy (History, EKG, physical, labs (detailed labs are listed under screening procedures))
    5. Weight between 44 and 115 kg (physical exam)
    6. Baseline systolic BP of < 150 and > 100, diastolic BP < 90 and >60 and baseline HR less than 90 (Physical exam)
  • SUBJECTS WITH SCHIZOPHRENIA Criteria (Assessment)

    1. Males or females between 18 and 35 years old (History)
    2. Fulfill DSM-V criteria for schizophrenic illness, schizophreniform or schizoaffective disorder (History, SCID)
    3. A negative urine toxicology with the exception of cannabis; in the case of a positive urine cannabis test a salivary cannabis test will be administered on the day of the PET scans to ensure subjects have not used within 24 - 48 hours.

      (Urine toxicology)

    4. Medically Healthy (History, EKG, physical, labs (detailed labs are listed in screening procedures))
    5. Clinical Global Impression-Severity scale (CGI-S) less than or equal to 4 (moderately ill).
    6. Off all medications for at least 1 week, does not wish to restart medications immediately and clinically stable while off medications. With the exception of lorazepam at a maximal dose of 2 mg QD, up to 24 h prior to the scans, and absence of injection of depot medication within the last 6 months (Interview and discussion with treating clinician)
    7. Weight between 44 and 115 kg (Physical exam)
    8. Baseline systolic BP of < 150 and > 100, diastolic BP < 90 and >60 and baseline HR less than 90 (Physical exam)

Exclusion Criteria:

  • HEALTHY CONTROLS

    1. Pregnancy or lactation, lack of effective birth control during 15 days before the scans* (Blood or Urine pregnancy test, history)
    2. Presence or positive history of serious medical or neurological illness, including low hemoglobin and seizure history.

      (Medical and neurological history, EKG, blood tests)

    3. Any current use (within past month) of amphetamines, opiates, cocaine, sedative-hypnotics, ecstasy PCP.

      (History, urine toxicology)

    4. Any use of cannabis beyond occasional use (i.e. more than 2 - 4 times per month) (History, saliva cannabis test)
    5. Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan (but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant. Dental fillings do not present a risk for MRI), as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock, PhD, Lippincott Williams and Wilkins, NY 2001. If there is any doubt, subjects will be excluded.

      (Interview and history)

    6. Lifetime exposure to radiation in the workplace; or participation in research protocols involving exposure to radiation within the previous year such that the total cumulative annual radiation dose (i.e., from participation in the previous research studies and this study) would exceed the radiation dose limits specified in the FDA regulations at 21 CFR 361.1, Radioactive Drugs Considered Generally Safe and Effective (i.e. annual cumulative radiation dose limit = 5 rems to gonads, blood-forming organs, lens of eye, whole body; 15 rems to other organs).

      (Interview and history)

    7. Medical history of chronic obstructive pulmonary disease or other chronic respiratory disorders (Medical history)
    8. More than one risk factor for coronary artery disease (smoking, cholesterol > 240 mg/dl, sedentary lifestyle) baseline SBP > 140 of DBP> 90) (History, physical examination and blood chemistry)
    9. Positive Allen Test indicating lack of collateral flow to hand (Physical Exam)
    10. Subjects with family history of a psychotic disorder, drug and alcohol Abuse/Dependence in first-degree relatives. (History)
  • SUBJECTS WITH SCHIZOPHRENIA Criteria (Assessment)

    1. DSM-V disorder other than schizophrenia, schizophreniform or schizoaffective disorder (History, SCID)
    2. Any current use (within past month) of amphetamines, opiates, cocaine, sedative-hypnotics, ecstasy PCP.

      (History, urine toxicology)

    3. Any use of cannabis beyond occasional use (i.e. more than 2 - 4 times per month) (History, saliva cannabis test)
    4. Antipsychotic medications in the last 3 weeks (6 months for depot medications) prior to the first PET scanning session.

      (History)

    5. Pregnancy or lactation, lack of effective birth control - OCP are allowed. (Pregnancy test, history)
    6. Presence or positive history of severe medical or neurological illness or any cardiovascular disease, low hemoglobin, and seizure history.

      (Medical and neurological history, neurological exam, EKG, blood chemistry)

    7. Lack of capacity to give informed consent (Interview)
    8. History of significant violent or suicidal behavior (Interview and review of records)
    9. Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan (but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant. Dental fillings do not present a risk for MRI), as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock, PhD, Lippincott Williams and Wilkins, NY 2001. If there is any doubt, subjects will be excluded.

      (Interview and history)

    10. Lifetime exposure to radiation in the workplace; or participation in research protocols involving exposure to radiation within the previous year such that the total cumulative annual radiation dose (i.e., from participation in the previous research studies and this study) would exceed the radiation dose limits specified in the FDA regulations at 21 CFR 361.1, Radioactive Drugs Considered Generally Safe and Effective (i.e. annual cumulative radiation dose limit = 5 rems to gonads, blood-forming organs, lens of eye, whole body; 15 rems to other organs).

      (Interview and history)

    11. Medical history of chronic obstructive pulmonary disease or other chronic respiratory disorders (Medical history)
    12. More than one risk factor for coronary artery disease (smoking, cholesterol > 240 mg/dl, sedentary lifestyle) baseline SBP > 140 of DBP> 90) (History, physical examination and blood chemistry)

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

コホートと介入

グループ/コホート
介入・治療
30人の健常者

[11C]NPA radiotracer, 2 injection per subject

Antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

[11C]raclopride radiotracer, 2 injections per subject

Antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

Dextroamphetamine, one oral administration of 0.5 mg/kg per subject Antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).
30 subjects with schizophrenia

[11C]NPA radiotracer, 2 injection per subject

Antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

[11C]raclopride radiotracer, 2 injections per subject

Antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

Dextroamphetamine, one oral administration of 0.5 mg/kg per subject Antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

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
base line Binding Potential (BPND)
時間枠:37 Days
PET outcome measure of the density of "available" neuroreceptors and the affinity of a drug to that neuroreceptor.
37 Days
percent change in BPND
時間枠:37 Days
Difference between BPND measured in the post-amphetamine condition (BPND AMPH) and BPND measured in the baseline condition (BPND BASE) expressed as a percentage of BPND BASE: BPND = 100 * (BPND AMPH - BPND BASE)/BPND BASE.
37 Days

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

捜査官

  • 主任研究者:William Frankle、New York Langone Health

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (予想される)

2019年7月1日

一次修了 (予想される)

2025年7月1日

研究の完了 (予想される)

2025年7月1日

試験登録日

最初に提出

2019年6月11日

QC基準を満たした最初の提出物

2019年6月25日

最初の投稿 (実際)

2019年6月26日

学習記録の更新

投稿された最後の更新 (実際)

2020年5月29日

QC基準を満たした最後の更新が送信されました

2020年5月27日

最終確認日

2020年5月1日

詳しくは

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

NPA radiotracerの臨床試験

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