TRIHEP3

Un estudio comparativo de fase 2 que evalúa la eficacia de la triheptanoína, una terapia anaplerótica en la enfermedad de Huntington

Completado

ACERCA DE

PATROCINADOR

Institut National de la Santé Et de la Recherche Médicale, France

PARTICIPANTES

100

En este ensayo se prueba un compuesto llamado triheptanoína para ver si tiene un impacto positivo en las funciones de los pacientes con EH en todas las áreas, pero con especial énfasis en las funciones cognitivas. El triheptanoion se produce artificialmente y es una grasa. Es casi insípido e incoloro y ya se utiliza como alimento médico para tratar ciertas enfermedades relacionadas con la producción de energía del cuerpo, los llamados trastornos metabólicos. Sabemos que la producción de energía de las células cerebrales se ve afectada negativamente en la EH. El ensayo incluye a 100 participantes. 50 recibirán triheptanoína cada día durante 12 meses. Los otros 50 participantes recibirán durante los primeros 6 meses un placebo. Pero durante los siguientes 6 meses recibirán triheptanoína. El efecto potencial se probará con MRS (resonancia magnetica) para obtener una imagen de si la producción de energía ha mejorado o al menos no ha disminuido. También se tomarán imágenes de resonancia magnética para ver cualquier efecto sobre el volumen cerebral. Además, los participantes serán sometidos a una batería de pruebas motoras y cognitivas, así como a cuestionarios relacionados con la capacidad funcional general y el estado psiquiátrico.

Fecha estimada de finalización del estudio: 31 de diciembre de 2020

Edades elegibles para el estudio:

18 años o más (adulto, adulto mayor)

Sexos elegibles para el estudio:

Todos

Acepta voluntarios sanos:

No

Criterios de inclusión

  • Prueba genética positiva con longitud de repetición CAG ≥39 en el gen HTT
  • Al menos 18 años de edad
  • Firma del consentimiento informado
  • Cobertura de la seguridad social
  • Puntuación UHDRS entre 5 y 40
  • Capacidad para someterse a una resonancia magnética
  • IMC entre 18 y 30

Criterios de exclusión

  • Hipersensibilidad a la triheptanoína o a uno de sus excipientes
  • Comorbilidades importantes adicionales
  • Antecedentes de lesiones graves en la cabeza
  • Participación en otro ensayo terapéutico (período de exclusión de 3 meses)
  • En el caso de las mujeres en edad fértil, ausencia de dos formas de anticoncepción eficaz (con la excepción de las abstinentes)
  • Embarazo o lactancia
  • Incapacidad para comprender la información sobre el protocolo
  • Personas privadas de libertad por decisión judicial o administrativa
  • Sujeto adulto bajo protección legal o incapaz de dar su consentimiento
  • Tratamiento con tetrabenazina

PAÍSES

FRANCIA

TRIAL SITE:
Département de Génétique

Address:Paris, France, 75013

Active, Not Recruiting

PAÍSES BAJOS

TRIAL SITE:
Department of Neurology

Address: Leiden, Netherlands, 2300RC

Active, Not Recruiting

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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.