PROOF-HD

Effet de la pridopidine sur la fonction dans la maladie de Huntington

Terminé

Mises à jour:

Le nouvel article de HDBuzz « Scientists identify precisely how pridopidine works in models of Huntington’s disease » par le Dr Rachel Harding apporte des nouvelles passionnantes sur l’étude potentielle PROOF-HD.

Article complet ici

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SPONSOR

Prilenia Neurotherapeutics  & Huntington Study Group

PARTICIPANTS

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PROOF-HD est une étude clinique de phase 3 qui évalue l’efficacité et l’innocuité de la pridopidine chez des patients présentant un stade précoce de la maladie de Huntington. La pridopidine est une petite molécule développée par Prilenia pour le traitement des troubles neurodégénératifs tels que la HD.

Selon Prilenia, la pridopidine est un médicament oral administré dans une petite capsule facile à avaler deux fois par jour, qui pénètre dans le cerveau et la moelle épinière, où il active une protéine appelée récepteur sigma-1 (S1R). L’activation du S1R par la pridopidine favorise la clairance des protéines toxiques, améliore la production d’énergie et réduit le stress cellulaire et l’inflammation. Ces mécanismes sont cruciaux pour la fonction et la survie des neurones.

Webinar : Tout ce que vous devez
savoir sur PROOF HD

Le Dr Michael Hayden présente la
phase 3 du projet PROOF-HD

Ages éligibles
pour l'étude:

25 ans et plus (adulte, adulte âgé)

Sexes éligibles
pour l'étude:

Tous

Accepte les volontaires en bonne santé:

Non

Critères d'inclusion

  1. Diagnostic de la MH basé sur les caractéristiques cliniques et la présence de répétitions ≥36 CAG dans le gène de la huntingtine.
  2. Niveau de confiance diagnostique (DCL) de 4
  3. HD à l’âge adulte avec apparition des signes et symptômes ≥18 ans.
  4. HD de stade 1 ou 2, définie par un score UHDRS-TFC de ≥7, lors du dépistage

Critères d'exclusion

  1. Utilisation de la pridopidine dans les 12 mois précédant la visite de référence.
  2. La thérapie génique à tout moment
  3. Tout état médical grave ou toute anomalie cliniquement significative des laboratoires ou des signes vitaux qui empêche le patient de participer en toute sécurité à l’étude et de la mener à bien, par exemple une maladie cardiaque importante dans les 12 semaines précédant l’inclusion ou des antécédents de certaines arythmies cardiaques.
  4. Antécédents d’épilepsie ou de crises d’épilepsie au cours des 5 dernières années
  5. Grossesse ou allaitement, ou intention de devenir enceinte pendant l’étude.

PAYS

COUNTRIES

Autriche

SITE D’ESSAI: Medizinische Universität Innsbruck

Adress: (Innsbruck

Contact: Dora Valent, Study Site Coordinator

Phone: 0512 504 83237
Email: dora.valent@tirol-kliniken.at

République Tchèque

SITE D’ESSAI:Centrum extrapyramidových onemocnění

Adress: Prague

Contact: Jiri Klempir, MD, Study Site Investigator
Tel:   +420  732 273 271
Email:  Jiri.Klempir@seznam.cz

France

SITE D’ESSAI: Centre Hospitalier Universitaire (CHU) Henri Mondor

Adress: Paris

SITE D’ESSAI: Centre Hospitalier Universitaire (CHU) Amiens-Picardie

Adress: Amiens

SITE D’ESSAI:Centre Hospitalier Universitaire (CHU) de Bordeaux

Adress: Bordeaux

Allemagne

SITE D’ESSAI: Euregional Huntington Center Aachen (EHZA) 

Adress: Aachen

Contact: Maha Sagar, Study Site Coordinator, Email: NeuroStudien@ukaachen.de Tel: +49 241 80 80697

SITE D’ESSAI: George Huntington Institut

Adress: Münster

Contact: Tel: +49 251 7887880
Email: info@ghi-muenster.de

SITE D’ESSAI: Huntington Center North Rhine-Westphalia,
Department of Neurology,
Ruhr-University Bochum,
St. Josef-Hospital Bochum

Adress: Bochum

Contact: Email: d.kaminski@klinikum-bochum.de
Tel.: +49-234-509-2703

SITE D’ESSAI: Kbo-Isar-Amper-Klinikum Taufkirchen (Vils)

Adress: Taufkirchen (Vils)

Contact: Michael Bachmaier, Study Site Coordinator
Email: Michael.Bachmaier@kbo.de
Tel: 08084-934-417

SITE D’ESSAI: University of Lübeck

Adress: Lübeck

Contact: Saruhi Surnaschjan, Study Site Coordinator 
Phone:+49 451 50043497
Email: saruhi.surnaschjan@neuro.uni-luebeck.de

SITE D’ESSAI: Ulm University

Adress: Ulm

Italie

SITE D’ESSAI: IRCCS Istituto delle Scienze Neurologiche di Bologna

Adress: Bologna

Contact: Tel: +393387367104
Email: unitastudiclinici@ausl.bologna.it

SITE D’ESSAI: Fondazione IRCCS Istituto Neurologico Carlo Besta

Adress: Milano

Contact: Tel: +39 02 23942519
Email: centroHD@istituto-besta.it

SITE D’ESSAI: CSS-Mendel Institute at IRCCS Casa Sollievo della Sofferenza Research Hospital

Adress: Roma

Contact: Tel: +39 06 44700887
Email: info@lirh.it

Les Pays-Bas

SITE D’ESSAI: Maastricht University

Adress: Maastricht 

Contact: Dr. Mayke Oosterloo, Study Site Investigator
Tel: 0031-(0)43-387 76 76, Email: expertisecentrumhuntington@mumc.nl

SITE D’ESSAI: Leiden University Medical Center

Adress: Leiden

Contact: Tel: 0031715265442 
Email: huntington@lumc.nl

Pologne

SITE D’ESSAI: Szpital Specjalistyczny Swietego Wojciecha

Adress: Gdansk

Contact: Agnieszka Konkel, Study Site Coordinator
Tel: +48 609 952 555
Email: konkel1989@gmail.com

SITE D’ESSAI: Instytut Psychiatrii i Neurologii

Adress: Warsaw

Contact: Grzegorz Witkowski, Study Site Investigator
Email: gwitkowski@ipin.edu.pl
Phone: +48694904208

SITE D’ESSAI: Krakowska Akademia Neurologii

Adress: Krakow

Contact: Email: centrum@neurologia.org.pl 
Tel: +48 12 426 92 80

Espagne

SITE D’ESSAI: Hospital de la Santa Creu i Sant Pau

Adress: Barcelona

Contact: Dr. Jaime Kulisevsky
Email: JKulisevsky@santpau.cat
Tel: +34 649 14 23 60

SITE D’ESSAI: Fundacion Hospital Universitario La Fé

Adress: Valencia

Contact: Francisco Castera, Study Site Coordinator
Email: franciscocasteraenroll@gmail.com

Carmen PEIRO, Study Site Investigator

Email: cpeirov@gmail.com
Tel: Phone: +34 682893185

SITE D’ESSAI: Burgos Foundation for Health Research

Adress: Burgos

Contact: Tel:  +34 947 28 18 00 ext 35380
Email: jessicajrp@hubu.es

mcubo@saludcastillayleon.es

SITE D’ESSAI: Hospital Ramón y Cajal

Adress: Madrid

Contact: Email: joselopezsendon@hotmail.com
Tel: +34  638 158 849

Royaume-Uni

SITE D’ESSAI: University of Aberdeen, Institute of Medical Sciences

Adress: Aberdeen (Scotland)

Contact: Stella Sihlabela, Study Site Coordinator
Tel: +44 1224 552120
Email: stella.sihlabela@nhs.scot

Resifina Seyara, Study Site Coordinator
Tel: +44 1224 552120
Email: resifina.seyara@nhs.scot

SITE D’ESSAI: Barberry National Centre for Mental Health

Adress: Birmingham (England)

SITE D’ESSAI: Cardiff University

Adress: Cardiff (Wales)

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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.