iMagemHTT

Evaluación FIH de nuevos radioligandos de PET de Huntingtina mutante [¹¹C] CHDI-00485180-R y [¹¹C] CHDI-00485626

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PATROCINADOR

CHDI Foundation, Inc.

PARTICIPANTES

84

El objetivo principal de este estudio es identificar si los llamados radioligandos (pequeñas partículas radiactivas) pueden detectar la huntingtina mutante (mHTT) en el cerebro. Este estudio de imagen se realiza en humanos y utiliza escáneres PET (imágenes) del cerebro para ver si la presencia de radioligandos se corresponde con la expresión de la huntingtina mutante en las células cerebrales. El objetivo del estudio es utilizar escáneres PET de radioligandos para medir la presencia de mHTT en las células cerebrales. Si se demuestra que es válido y que es una forma eficaz de medir la mHTT, puede utilizarse para medir si las terapias de reducción de la huntingtina realmente reducen la mHTT en el cerebro. Este estudio es importante y necesita voluntarios porque todavía no tenemos ningún método para medir si las terapias reductoras de la huntingtina llegan realmente al tejido cerebral donde se necesitan y si los niveles de mHTT se reducen.

Fecha estimada de finalización del estudio: Enero de 2023

Edades elegibles
para el estudio:

20 años a 65 años

(adulto, adulto mayor)

Sexos elegibles
para el estudio:

Todos

Acepta voluntarios sanos:

Si

Criterios de inclusión:

HDGEC premanifestado, HDGEC con etapa I HD, HDGEC con participantes en etapa II HD y HC:

  • Hombres y mujeres adultos, de 20 a 65 años, inclusive.
  • Índice de masa corporal (IMC) entre 19 y 35 inclusive.
  • Capacidad para dar su consentimiento informado completo por escrito, y haber leído y firmado el formulario de consentimiento informado (CIF).
  • Son capaces de cumplir con los procedimientos del estudio, incluido el ayuno y la toma de muestras de sangre.
  • Capaz y dispuesto a viajar al centro de imágenes PET en Lovaina, Bélgica.
  • Dispuesto a cumplir con el uso de medidas anticonceptivas adecuadas.

HDGEC premanifestados:

  • No tienen características motoras de diagnóstico clínico de la EH, definidas como Escala unificada de calificación de la enfermedad de Huntington (UHDRS) Puntuación de confianza diagnóstica <4; y
  • Tener expansión CAG ≥ 40; y
  • Tener un puntaje CAP> 70 (calculado con la fórmula CAP: EDAD * (CAG – 30) / 6.49).

HDGEC con etapa I HD:

  • Tienen características motoras de diagnóstico clínico de HD, definidas como UHDRS Diagnostic Confidence Score = 4; y
  • Tener expansión CAG ≥ 40; y
  • Tener Etapa I HD, definida como puntajes de Capacidad Funcional Total (TFC) UHDRS entre 11 y 13 inclusive.

HDGEC con Stage II HD:

  • Tienen características motoras de diagnóstico clínico de HD, definidas como UHDRS Diagnostic Confidence Score = 4; y
  • Tener expansión CAG ≥ 40; y Tener Etapa II HD, definida como puntajes de Capacidad Funcional Total (TFC) UHDRS entre 7 y 10 inclusive.

Participantes de HC:

  • No tiene antecedentes familiares conocidos de HD
  • Tienen antecedentes familiares conocidos de HD, pero se les ha examinado la expansión del codón de glutamina (CAG) del gen de la huntingtina y no tienen riesgo genético de HD (CAG <36).
  • Emparejado por edad +/- 5 años.
  • (Fase 1 solamente) menores de 35 años.

Criterios de exclusión:

HDGEC premanifestado, HDGEC con Etapa I HD, HDGEC con Etapa II HD y participantes de HC:

  • Actualmente participando en o menos de 30 días después de completar la participación en otros estudios terapéuticos o de imágenes.
  • Participación previa en un estudio de imágenes de PET que, en conjunto con el estudio actual, superará los límites reglamentarios anuales para la exposición a la radiación.
  • Cualquier enfermedad, afección o medicación concomitante que comprometa significativamente la función de los sistemas corporales y que, en opinión del Investigador, pueda interferir con la realización del estudio o su interpretación.
  • Mujeres embarazadas y en período de lactancia.
  • Uso de medicación concomitante (ConMed) de terapia antiplaquetaria o anticoagulante (incluido el ácido acetilsalicílico). (Consulte la lista completa de ConMed adjunta).
  • Fobia a las agujas.

Participantes de HDGEC:

  • Si usa algún antidepresivo, psicoactivo, psicotrópico u otros medicamentos o nutracéuticos utilizados para tratar la EH, el uso de una dosis inapropiada (por ejemplo, no terapéuticamente alta) o inestable dentro de los 30 días anteriores a la participación.

Participantes de HC:

  • Antecedentes familiares de EH (a menos que una prueba genética confirme resultados negativos).

Para los participantes en la recolección de muestras de LCR opcional:

  • Dolor de cabeza frecuente, deformidad significativa de la columna inferior o cirugía mayor; o
  • Desorden sangrante.

PAÍSES

PAÍSES

CONTACTO

Illona Feldman
Tel.: 609-945-9629
illona.feldman@chdifoundation.org

BÉLGICA

Lugar:
Universitaire Ziekenhuizen Leuven/ UZ Leuven/ UZL

Dirección: Leuven, Belgium, 3000

CONTACTO
Wim Vandenberghe
Tel: 32 16344280
wim.vandenberghe@uzleuven.be  

Koen Van Laere
Tel: 32 16 34 37 11
koen.vanlaere@uzleuven.be

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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.