EIP19-NFD-401

ESTUDIO CRUZADO CON SUJETOS SOBRE LOS EFECTOS COGNITIVOS DEL NEFLAMAPIMOD EN LA ENFERMEDAD DE HUNTINGTON EN FASE INICIAL

Terminado

ACERCA DE

PATROCINADOR

EIP Pharma Inc

PARTICIPANTES

16 Participantes

El objetivo principal del EIP19-NFD-401 es determinar si un fármaco llamado Neflamapimod puede mejorar las funciones cognitivas (planificación, memoria, etc.) en pacientes con la enfermedad de Huntington (EH) en fase inicial. El fármaco se toma por vía oral. En el estudio, 16 pacientes recibirán el fármaco durante 10 semanas y luego se les administrará un placebo durante 10 semanas o viceversa. Ni el médico ni el paciente saben en qué periodo reciben el fármaco activo o el placebo. El efecto se comprobará con diferentes pruebas cognitivas. El neflamapimod se dirige a una enzima del cerebro llamada p38 alfa. El objetivo es reducir la expresión de la enzima en las neuronas y permitir que las células funcionen mejor. El fármaco ha demostrado un efecto prometedor en pruebas con animales y actualmente también se está probando en pacientes con la enfermedad de Alzheimer.

Estudio terminado (Debido al largo retraso por el COVID-19 y a los resultados de otro estudio que sugieren que una dosis más alta puede ser más beneficiosa, EIP Pharma decidió el 15 de octubre de 2020 terminar el ensayo prematuramente).

Edades elegibles del estudio:

30 años a 70 años (adulto, adulto mayor)

Sexos elegibles para el estudio:

Todos

Acepta voluntarios saludables:

No

Criterios de inclusión:

  • Hombres y mujeres de 30 a 70 años, inclusive.
  • Dispuesto y capaz de dar su consentimiento informado.
  1. Debe tener EH genéticamente confirmada y déficits cognitivos identificados:
  2. Etapa 1, según la definición de la Escala de calificación de la enfermedad de Huntington unificada (UHDRS) Puntaje de capacidad funcional total (TFC)> 10, y
  • CANTAB Paired Associate Learning Puntuación de error ajustada total de> 16.
  • Habilidades visuales y auditivas normales o corregidas, suficientes para realizar todos los aspectos de las evaluaciones cognitivas y funcionales.
  • Sin antecedentes de dificultades de aprendizaje que puedan interferir con la capacidad del sujeto para completar las pruebas cognitivas.

Criterio de exclusión:

  • Un perfil de deterioro que no es compatible con la EH.
  • Diagnóstico de cualquier otra afección del sistema nervioso central en curso que no sea la EH, que incluye, entre otros, demencia vascular, demencia con cuerpos de Lewy y enfermedad de Parkinson.
  • Suicidalidad, definida como pensamientos suicidas activos dentro de los 6 meses previos a la selección o al inicio, definida como responder sí a los ítems 4 o 5 en la escala Columbia-Suicide Severity Rating Scale (C-SSRS), o antecedentes de intento de suicidio en los 2 años anteriores, o , en opinión del investigador, en grave riesgo de suicidio.
  • Trastorno psiquiátrico mayor y activo en curso, síntomas depresivos de moderados a graves u otra afección médica concurrente que, en opinión del investigador, podría comprometer la seguridad y / o el cumplimiento de los requisitos del estudio.
  • Diagnóstico de abuso de alcohol o drogas en los 2 años anteriores.
  • Enfermedad médica clínicamente significativa mal controlada, como hipertensión (presión arterial> 180 mmHg sistólica o 100 mmHg diastólica); infarto de miocardio dentro de los 6 meses; Insuficiencia cardíaca congestiva no compensada u otras enfermedades cardiovasculares, pulmonares, renales, hepáticas, infecciosas, trastornos inmunitarios o trastornos metabólicos / endocrinos importantes u otras enfermedades que impidan el tratamiento con inhibidor de quinasa de proteína activada por mitógeno p38 (MAP) y / o evaluación de la seguridad del fármaco y eficacia.
  • Anemia con hemoglobina ≤10 g / dL, anomalía clínicamente significativa de la función tiroidea, anomalías electrolíticas.
  • Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT)> 1,5 × el límite superior de la normalidad (LSN), bilirrubina total> 1,5 × LSN y / o índice normalizado internacional (INR)> 1,5.
  • Virus de inmunodeficiencia humana conocido; o infección activa por el virus de la hepatitis B o la hepatitis C; evidencia de tuberculosis activa o latente.
  • El sujeto participó en un estudio de un fármaco en investigación durante menos de 3 meses o 5 vidas medias de un fármaco en investigación, lo que sea más largo, antes de la inscripción en este estudio.
  • Historia de neurocirugía previa al cerebro.
  • Mujeres embarazadas o en período de lactancia.
  • Sujetos masculinos con parejas femeninas en edad fértil que no desean o no pueden cumplir con los requisitos de anticoncepción especificados en el protocolo (ver Sección 5.8).
  • Mujeres que no han alcanzado la menopausia o que no han tenido una histerectomía o una ooforectomía / salpingooforectomía bilateral y no están dispuestas o no pueden cumplir con los requisitos anticonceptivos especificados en el protocolo (ver Sección 5.8).
  • Requiere el uso concomitante de inhibidores del citocromo P450 (CYP) 3A4 o terapias anti-factor de necrosis tumoral alfa durante la participación en el estudio.
  • Alergia conocida a cualquier ingrediente del medicamento de prueba o placebo.

PAÍSES

REINO UNIDO

Lugar:
John Van Geest Centre for Brain Repair

Dirección: Cambridge, United Kingdom, CB2 0PY

CONTACTO
Danielle Daft
Tel: 01223 334121

EIP Pharma
Jennifer Conway
Tel: 617-945-0794
jconway@eippharma.com

Reclutando

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phenoptype

Phenotype refers to an individual’s observable traits, such as height, eye color and blood type. A person’s phenotype is determined by both their genomic makeup (genotype) and environmental factors.

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oxidative seres

an imbalance between unstable molecules called «free radicals» and protective «antioxidants» in your body

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Metabolism & bioenergetics

describe how your body turns food into fuel and uses that energy to live. 

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Small Molecule

a tiny chemical compound, much smaller than big biological structures like proteins, that can easily travel inside our cells to act as medicine (like aspirin or ibuprofen), a building block (like glucose), or a signaling tool in the body, often taken as pills because they’re easy to absorb and distribute

 

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Nucleic acid

(DNA and RNA) are the essential information-carrying molecules in all life, acting like blueprints that store and transmit genetic instructions for building and operating cells, directing everything from growth to protein production, and passing traits from parents to offspring.

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SNP-single nucleotide polymorphisms

a single-letter spelling difference in a gene. SNPs, pronounced ‘snips’, are common and most don’t change the function of the gene.

 
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at risk

You do not know if you carry the genetic mutation for HD gene 

 
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TFC-total functional capacity

A standardized rating scale for function in HD, used to assess capacity to work, handle finances, perform domestic chores and self-care tasks.
Scores range from 0 to 13, with higher scores indicating better functional capacity. 

 
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Double-blinded

 means that neither the participant nor the clinical trial doctor can choose or know the group the participant is in until the trial is over. This approach helps to prevent bias.

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Open label

A trial in which the patient and doctor know what drug is being used. Open label trials are susceptible to bias through placebo effects.

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Gene therapy

a technique that aims to treat or prevent diseases by modifying a person’s genes. It involves introducing, removing, or changing genetic material (DNA or RNA) within a patient’s cells.

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UHDRS- Unified Huntington Disease Rating Scale

A standardized neurological examination that aims to provide a uniform assessment of the clinical features of HD

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CAG repeat

The stretch of DNA at the beginning of the HD gene, which contains the sequence CAG repeated many times, and is abnormally long in people who will develop HD

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Wild-type

the opposite of ‘mutant’. Wild-type huntingtin, for example, is the ‘normal’, ‘healthy’ protein

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Tolerabilty

How well a person can handle a treatment without having serious or uncomfortable side effects.

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Striatum

Part of the brain that  coordinates multiple aspects of cognition, including both motor and action planning, decision-making, motivation, reinforcement, and reward system.

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Randomized allocation

A type of allocation strategy in which participants are assigned to the arms of a clinical trial by chance.

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Radioligand

a radioactive substance that binds to a specific target in the body, allowing visualization of that target’s distribution and activity

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Protein

Protein builds, maintains, and replaces the tissues in your body. The building blocks of life.

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Premanifest / Prodromal

Prior to onset or diagnosis of movement symptoms.

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Placebo

A placebo is a dummy medicine containing no active ingredients. The placebo effect is a psychological effect that causes people to feel better even if they’re taking a pill that doesn’t work.

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PK - Pharmacokinetics

The movement of drugs through the body

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PD - Pharmacodynamics

The body’s biological response to drugs

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PET scan

Positron emission tomography which produces detailed 3-dimensional images of the inside of the body.

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Neuron

Brain cells that store and transmit information

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MRI

Magentic resonance imaging: A technique using powerful magnetic fields to produce detailed images and visualizes the structure of organs, tissues, and bones 

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mHTT

Mutant huntingtin protein. The protein produced by the faulty HD gene.

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Manifest

after HD diagnosis, or when symptoms are already showing

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Longitudinal study

A study where each participant is looked at several times over a time period – unlike a cross-sectional study, where each participant is looked at only once

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HTT

one abbreviation for the gene that causes Huntington’s disease. The same gene is also called HD and IT-15

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fMRI

functional MRI:As with MRI, a technique using powerful magnetic fields  but focusing on brain function by measuring and mapping changes in blood flow, revealing which areas of the brain are active during specific tasks or cognitive processes

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CSF - cerebrospinal fluid

A clear fluid produced by the brain, which surrounds and supports the brain and spinal cord.

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Efficacy

A measure of whether a treatment works or not

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ASO(Antisense oligonucleotides)

A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene

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Biomarker

a test of any kind – including blood tests, thinking tests and brain scans – that can measure or predict the progression of a disease like HD. Biomarkers may make clinical trials of new drugs quicker and more reliable

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BDNF

Brain-derived neurotrophic factor: a growth factor that may be able to protect neurons in HD.

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Allele

one of the two copies of a gene

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Plasma

Liquid component of the blood.

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Gene

The basic unit of heredity passed from parent to child. Genes are made up of sequences of DNA and are arranged, one after another, at specific locations on chromosomes in the nucleus of cells.

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Phase

Clinical trial phases are different stages of research that assess the safety and effectiveness of a new medical treatment or intervention in humans.

Each phase has a specific goal and involves a different number of participants. Generally, there are 4 phases (I-IV), with Phase I focusing on safety and dosage, Phase II on efficacy and side effects, Phase III on comparing the new treatment with standard treatments, and Phase IV on long-term safety monitoring.