Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
7 de julio de 2020 actualizado por: Jeffrey Newcorn, Icahn School of Medicine at Mount Sinai
The growing number of medications used to treat attention-deficit/hyperactivity disorder (ADHD) raises important questions about whether different medications have similar or different therapeutic mechanisms of action.
We have recently shown that the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline cingulate-precuneus regions.
These exciting findings offer a window into the common and unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments.
However, the interpretation and clinical utility of these results would be greatly enhanced by in-depth investigation of the impact of the two treatments on relevant neural networks, and analyses which evaluate whether improvement is achieved via normalization or other adaptive changes in brain function.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to determine the significance of activation changes over treatment related to clinical improvement, and the impact of treatment on neural connectivity within and between the anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus 'task-negative' network. Our central hypotheses are that clinical improvement is associated with: (i) normalization of reduced connectivity of regions within the 'task-positive' network, with resultant increased inhibition of motor cortex, and (ii) normalization of low task-related connectivity in regions within the task-negative network for MPH and the 'task-positive' network for ATX.
This research proposes to test a model which posits a neurophysiological basis of mechanisms of response to stimulant and non-stimulant medications, and fits with our long term objectives of being able to match treatments to individual patients. Testing this model requires large samples of youth scanned using fMRI before and after treatment, and matched healthy controls also scanned twice. We will use an innovative network-based approach to study the effects of treatment, building on results from our current fMRI treatment study, and incorporating new theoretical approaches to understanding ADHD and its treatment.
Tipo de estudio
Intervencionista
Inscripción (Actual)
127
Fase
- Fase 4
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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New York
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New York, New York, Estados Unidos, 10029
- Icahn School of Medicine at Mount Sinai
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
7 años a 17 años (Niño)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
General inclusion criteria for subjects with ADHD and healthy controls are:
- aged 7-17 years;
- Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;
- informed consent and assent to study participation.
Specific inclusion criteria for youth with ADHD are:
- diagnosis of ADHD, any subtype, determined by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Versions (K-SADS-PL);
- ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD-RSIV) total score ≥ 1.5 SD above age and gender means for subtype
- Clinical Global Impressions-ADHD-Severity (CGI-S) score > 4;
- ADHD must be the primary diagnosis and focus of treatment, and the treatments offered in the study must not be contraindicated for the comorbid disorder.
Exclusion Criteria:
General exclusion criteria are:
- history of head injury with loss of consciousness or any CNS disease that is likely to affect brain function;
- diagnosis of autism or pervasive developmental, psychotic, major mood, and Tourette's disorder;
- alcohol or drug abuse in the past 3 months or a positive urinary toxic screen on initial evaluation;
- use of psychotropic medication within 2 weeks of the study (8 weeks for fluoxetine);
- pre-existing medical or psychological condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity);
- metal in the body that precludes scanning (e.g., braces, metal plate);
- positive urine pregnancy test.
Specific exclusion criteria for the treatment trial include:
- previous unsuccessful trial of MPH or ATX that was adequately dosed (≥ 1 mg/kg for MPH or 1.0 mg/kg for ATX) and of adequate duration (≥ 4 weeks);
- abnormal findings on physical exam, or vital signs
- pulse and blood pressure > 95% of age and gender mean;
- inability to swallow capsules;
- weight is < 20 kg or > 85 kg.
Specific exclusion criteria for control youth include:
- no past history or current diagnosis of any psychiatric disorder, determined by the K-SADS-PL interview;
- ADHD-RS-IV and CBCL scores for each symptom domain ≤ 1 SD of age and gender means.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: fMRI scans
Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart
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2 fMRI scans 6-8 weeks apart
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Experimental: Atomoxetine arm
These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.
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2 fMRI scans 6-8 weeks apart
Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks
Otros nombres:
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Experimental: Methylphenidate arm
Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.
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2 fMRI scans 6-8 weeks apart
Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task
Periodo de tiempo: Baseline and at 6 weeks
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Comparison of Go-Nogo at 6 weeks from baseline.
Performance on a go-nogo task inside the scanner (fMRI).
In the go/no-go task, participants respond to certain stimuli ("go" stimuli) and make no response for others ("no-go" stimuli).
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Baseline and at 6 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)
Periodo de tiempo: 8 weeks
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ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.
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8 weeks
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Clinical Global Impressions-Severity (CGI-S)
Periodo de tiempo: up to 6 weeks
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a clinician rated measure of symptom severity.
CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.
Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
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up to 6 weeks
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Response Time in Attention Networks Test (ANT)
Periodo de tiempo: baseline and at 6 weeks
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A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time.
The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control.
The response time were summed.
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baseline and at 6 weeks
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Continuous Performance Test (CPT)
Periodo de tiempo: baseline and at 6 weeks
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A neuropsychological assessment of attention compared at 6 weeks from baseline.
CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented.
A fast reaction time and high commission error rate points to difficulties with impulsivity.
A slow reaction time with high commission and omission errors, indicates inattention in general.
Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score.
The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age.
A T-score of 50 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values are indicative of more attention-related problems.
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baseline and at 6 weeks
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Digit Span
Periodo de tiempo: baseline and at 6 weeks
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A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline.
Digit Span.
Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials.
Items may include words, numbers, or letters.
The task is known as digit span when numbers are used.
Memory span is a common measure of short-term memory.
A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2).
The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points.
Higher score indicates better health outcomes.
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baseline and at 6 weeks
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Finger Windows
Periodo de tiempo: baseline and at 6 weeks
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A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline.
The Finger Windows subtest is a measure of nonverbal, rote sequential recall.
scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.
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baseline and at 6 weeks
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Kurt Schulz, PhD, Icahn School of Medicine at Mount Sinai
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de octubre de 2012
Finalización primaria (Actual)
30 de abril de 2018
Finalización del estudio (Actual)
30 de abril de 2018
Fechas de registro del estudio
Enviado por primera vez
30 de agosto de 2012
Primero enviado que cumplió con los criterios de control de calidad
30 de agosto de 2012
Publicado por primera vez (Estimar)
3 de septiembre de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
24 de julio de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
7 de julio de 2020
Última verificación
1 de julio de 2020
Más información
Términos relacionados con este estudio
Palabras clave
- Adolescente
- Tratamiento
- Imágenes
- Concierto
- Imágenes de resonancia magnética funcional
- Desorden hiperactivo y deficit de atencion
- Imagen mental
- Juventud
- Metilfenidato
- Medicamento
- Droga
- Estimulante
- No estimulante
- Atomoxetina
- Strattera
- MACRO
- Escaneo cerebral
- Inhibición de respuesta
- Inatento
- Hiperactivo
- Conjunto
- Medication Treatment
Términos MeSH relevantes adicionales
- Desordenes mentales
- Enfermedades del Sistema Nervioso
- Manifestaciones neurológicas
- Discinesias
- Trastornos por Déficit de Atención y Conducta Disruptiva
- Trastornos del neurodesarrollo
- Trastorno por Déficit de Atención con Hiperactividad
- Hipercinesia
- Efectos fisiológicos de las drogas
- Agentes adrenérgicos
- Agentes neurotransmisores
- Mecanismos moleculares de acción farmacológica
- Inhibidores de la captación de neurotransmisores
- Moduladores de transporte de membrana
- Agentes de dopamina
- Inhibidores de la captación de dopamina
- Estimulantes del Sistema Nervioso Central
- Inhibidores de la captación adrenérgica
- Metilfenidato
- Clorhidrato de atomoxetina
Otros números de identificación del estudio
- GCO 11-0161
- 5R01MH095766-02 (Subvención/contrato del NIH de EE. UU.)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .