- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT03983252
Effect of Alemtuzumab on Microglial Activation Positron Emission Tomography (PET) in Multiple Sclerosis
Effect of Alemtuzumab on Microglial Activation Assessed Using Novel [F-18]-Based Positron Emission Tomography (PET) Ligand in Multiple Sclerosis
Specific Aims
The specific aims of the study are:
- Primary Objective: To assess the effect of alemtuzumab on microglial activation in MS patients. The hypothesis is that alemtuzumab reduces microglial activation in MS, which may mediate its effect on reducing conversion of RRMS patients to SPMS, and its effects on cognition, including cognitive fatigue.
- Secondary Objective: To determine the time course of effect of alemtuzumab on microglial activation. The hypothesis is that alemtuzumab reduces microglial activation at 6 months after initiation of treatment and this effect persists and is accentuated at 18 years, i.e. after administration of the second course
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
I. Subject Selection
Subjects will be recruited at the Partners MS Center, 60 Fenwood Road, Boston, MA. In addition, referrals for the study will be obtained from MS Center at University of Massachusetts Medical center, Worcester, MA. Subjects will also be recruited through Health and Clinical Research OnCall websites, and from individual physician references.
II. Study Procedures
Initial Visit:
During the first visit, subjects will be adminsitered a screening questionnaire. Subjects will review and eventually sign the consent form. They will be administered standardized questionnaires for cognitive testing and/or other co-morbidities. In addition, a blood sample will be drawn for genotype testing to identify high affinity, medium affinity and low affinity binders.
Genotype Testing Blood sample drawn on the initial screening visit will be used to obtain genomic DNA for genotyping for polymorphism within the TSPO gene on chromosome 22q13.2, using a Taqman assay. High affinity and medium affinity binders will be included in the study while the low affinity binders will be excluded from the study. The blood sample will also be assessed for serum creatinine and estimated GFR because these subjects would need to undergo intravenous gadolinium contrast administration with their 3T MRIs. Blood samples will be stored for future immunophenotyping and/or other blood assays in the future.
PET Visits:
During the PET scan visits, all women subjects of child bearing age will undergo a stat quantitative serum hCG pregnancy test and only women with a negative test will undergo the radiopharmaceutical injection.
PET imaging procedures
PET scanning session will be at BWH PET scanning facility, 75 Francis Street, Boston, MA.
For PET scanning, an intravenous (IV) catheter will be inserted into the radial antecubital or other arm or hand vein for injection of tracer. Radiopharmaceutical will be injected as a bolus (approximately 4mCi for [F-18]PBR06) followed by 5 mL of saline. At the time of imaging, the subjects will be positioned in the gantry of a PET camera. Head alignment will be made, relative to the canthomeatal line, using projected laser lines whose positions are known with respect to the slice positions of the scanner. A head support apparatus will be used to minimize head motion. Brain PET data acquisition will begin at the moment of radiotracer injection. Images will be acquired using a high-resolution PET/CT scanner.
MRI Visit(s):
All subjects will undergo a 3T Brain MRI during an MRI visit that may precede or follow the PET scan visit(s) but will be perfromed within 2 weeks of each other.
MRI imaging procedures MRI scanning session will be performed at BWH MRI facility at 60 Fenwood Road, Boston, MA. MRIs will be performed with and without intravenous gadolinium-based contrast.
Imaging Data
The following data will be collected on all subjects during scanning sessions:
During PET scanning, brain images will be acquired in 3-D mode, and dynamic acquisition scans will continue for 120 minutes. A non-diagnostic CT scan will be performed for attenuation correction of PET transmission data at the time of initiation of scanning. MRI data will be acquired as described above. T2/ FLAIR and other MRI images will be coregistered with PET images
. Non Imaging/Clinical Data
The following non-imaging/clinical data will be obtained:
Expanded Disability Status Scale (EDSS) Timed 25-feet walk (T25W) MS Functional Composite (MSFC) Minimal Assessment of Cognitive Function Scale in MS (MACFIMS) battery Symbol digit modalities test (SDMT) MSQOL-54 scale (QOL) Modified fatigue Impact Scale (MFIS) Pittsburgh Sleep Quality Index (PSQI) Beck's Depression Inventory (BDI) Center for Epidemiological Studies-Depression Scale (CES-D) Hospital Anxiety and Depression Scale (HADS)
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Tarun Singhal, MD
- Número de telefone: 203-804-5131
- E-mail: tsinghal@bwh.harvard.edu
Locais de estudo
-
-
Massachusetts
-
Boston, Massachusetts, Estados Unidos, 02115
- Partners MS Center, 60 Fenwood Road
-
Contato:
- Steven Cicero
- Número de telefone: 617-264-3044
- E-mail: scicero@bwh.harvard.edu
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Patients with Relapsing Remitting Multiple Sclerosis (RRMS) (defined by International Panel Criteria)
- Age 18-60 years
- Enrolled to start treatment with alemtuzumab
Exclusion Criteria:
- Relapse/Corticosteroid treatment in the past 4 weeks to avoid transient effects on imaging
- Individuals with a known alternate neurologic disorder, previous head injury, or substance abuse.
- Individuals with bipolar disease and schizophrenia
- Concurrent medical conditions that contraindicate study procedures.
- Women who are pregnant or nursing. Also, any woman who is seeking to become pregnant or suspects she is pregnant will be excluded from enrollment.
- Claustrophobia
- Non-MRI compatible implanted devices
- Low affinity binder
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Diagnóstico
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
---|---|
Experimental: Relapsing Remitting Multiple Sclerosis starting Alemtuzumab
Patients with Relapsing Remitting Multiple Sclerosis (RRMS) (defined by International Panel Criteria), age 18-60 years, enrolled to start treatment with alemtuzumab. Subjects will undergo [F-18]PBR06 PET scans at baseline, 6 months and 18 months. |
PET radiofármaco
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
PET Uptake/Standardized uptake value ratio (SUVR) change
Prazo: baseline and 18 months
|
PET outcome measure change at 18 months from baseline
|
baseline and 18 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
PET Uptake/Standardized uptake value ratio (SUVR) change
Prazo: baseline and 6 months
|
PET outcome measure change at 6 months from baseline
|
baseline and 6 months
|
T2/FLAIR lesion load change
Prazo: baseline and 18 months
|
MRI outcome measure change at 18 months from baseline
|
baseline and 18 months
|
Whole brain/deep gray matter atrophy change
Prazo: baseline and 18 months
|
MRI outcome measure change at 18 months from baseline
|
baseline and 18 months
|
Expanded Disability Status Scale (EDSS) change
Prazo: baseline and 18 months
|
Clinical outcome measure change at 18 months from baseline; Scale Range: 0-10; Higher values represent worse outcomes
|
baseline and 18 months
|
Timed 25-foot walk (T25FW) change
Prazo: baseline and 18 months
|
Clinical outcome measure change at 18 months from baseline
|
baseline and 18 months
|
Modified Fatigue Impact Scale (MIFS) change
Prazo: baseline and 18 months
|
Clinical outcome measure change at 18 months from baseline; Physical subscale range: 0-36; Cognitive subscale range: 0-40; Psychosocial subscale range: 0-8; Total MFIS Score scale range (Subscales Summed): 0-84; Higher values represent worse outcomes
|
baseline and 18 months
|
Minimal Assessment of Cognitive Function in MS (MACFIMS) change
Prazo: baseline and 18 months
|
Clinical outcome measure change at 18 months from baseline
|
baseline and 18 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Tarun Singhal, MD, Brigham and Women's Hospital
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Antecipado)
Conclusão Primária (Antecipado)
Conclusão do estudo (Antecipado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 2018A019732
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
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 .
Ensaios clínicos em [F-18]PBR06
-
Brigham and Women's HospitalConcluído
-
Brigham and Women's HospitalBiohaven Pharmaceuticals, Inc.ConcluídoAtrofia de Múltiplos Sistemas | Atrofia de Múltiplos Sistemas, Variante de Parkinson (Transtorno) | Atrofia de Múltiplos Sistemas, Variante Cerebelar | Atrofia de múltiplos sistemas (MSA) com hipotensão ortostáticaEstados Unidos
-
Brigham and Women's HospitalDesconhecidoEsclerose múltipla | Doença de AlzheimerEstados Unidos
-
Brigham and Women's HospitalNovartisRecrutamentoEsclerose Múltipla RecidivanteEstados Unidos
-
Brigham and Women's HospitalU.S. Army Medical Research Acquisition ActivityRecrutamentoEsclerose múltiplaEstados Unidos
-
Chang Gung Memorial HospitalConcluído
-
Chang Gung Memorial HospitalConcluídoDemência frontotemporal | Paralisia Supranuclear Progressiva | Doença de Alzheimer | Comprometimento Cognitivo Vascular | Síndrome Cortical BasalTaiwan
-
Siemens Molecular ImagingFudan UniversityConcluídoCâncer de Cabeça e Pescoço | Câncer de pulmão | Câncer de fígadoChina
-
John M. BuattiNational Cancer Institute (NCI); National Institutes of Health (NIH)ConcluídoNeoplasias do colo uterino | Neoplasias prostáticas | Neoplasias retais | Neoplasias endometriais | Neoplasias do ânusEstados Unidos
-
Siemens Molecular ImagingConcluído