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Imaging Dopamine D2 Agonist Binding Sites in Schizophrenia

27 de maio de 2020 atualizado por: 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.

Visão geral do estudo

Descrição detalhada

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.

Tipo de estudo

Observacional

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

    • New York
      • New York, New York, Estados Unidos, 10016
        • NYU Langone Health

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 35 anos (Adulto)

Aceita Voluntários Saudáveis

Sim

Gêneros Elegíveis para o Estudo

Fêmea

Método de amostragem

Amostra Não Probabilística

População do estudo

SCHIZOPHRENIA patiens 18-35; Healthy Controls 18-35

Descrição

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)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Coortes e Intervenções

Grupo / Coorte
Intervenção / Tratamento
30 controles saudáveis

[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).

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
base line Binding Potential (BPND)
Prazo: 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
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Investigadores

  • Investigador principal: William Frankle, New York Langone Health

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Antecipado)

1 de julho de 2019

Conclusão Primária (Antecipado)

1 de julho de 2025

Conclusão do estudo (Antecipado)

1 de julho de 2025

Datas de inscrição no estudo

Enviado pela primeira vez

11 de junho de 2019

Enviado pela primeira vez que atendeu aos critérios de CQ

25 de junho de 2019

Primeira postagem (Real)

26 de junho de 2019

Atualizações de registro de estudo

Última Atualização Postada (Real)

29 de maio de 2020

Última atualização enviada que atendeu aos critérios de controle de qualidade

27 de maio de 2020

Última verificação

1 de maio de 2020

Mais Informações

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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