Estimulación cerebral profunda (ECP)

del Globus Pallidus (GP) en la enfermedad de Huntington (EH) (HD-DBS)

Completado

Información

Patrocinadores

Heinrich-Heine University, Duesseldorf

Participantes

50

El objetivo principal de este estudio es investigar si la estimulación cerebral profunda tiene un efecto positivo sobre los síntomas motores y cognitivos en los pacientes de Huntington. La estimulación cerebral profunda (ECP) es una cirugía para implantar un dispositivo que envía señales eléctricas a las zonas del cerebro responsables del movimiento del cuerpo. Los electrodos se colocan en la profundidad del cerebro y se conectan a un dispositivo estimulador. Al igual que un marcapasos, un neuroestimulador utiliza impulsos eléctricos para regular la actividad cerebral. El tratamiento con ECP se ha utilizado en algunas personas con la enfermedad de Parkinson. En este estudio se investigará tanto la seguridad como la eficacia con 50 participantes. 25 participantes serán estimulados con el ECP durante un primer periodo de 3 meses y su rendimiento en una serie de pruebas, se comparará con el de los 25 participantes que no reciban ninguna estimulación. Después de los primeros 3 meses, todos los participantes serán tratados con la ECP durante otros 3 meses.

Fecha estimada de finalización del estudio: 31 de diciembre de 2022

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

  • EH clínicamente sintomática y genéticamente confirmada (número de repeticiones CAG ≥ 36)
  • Edad ≥18 años
  • Estadio moderado de la enfermedad (puntuación motora UHDRS ≥ 30)
  • Corea a pesar del mejor de los tratamientos médicos (subpuntuación de la corea UHDRS ≥ 10)
  • Escala de valoración de la demencia de Mattis ≥ 120 (o > 80% de los ítems comprobables independientemente del deterioro motor)
  • El paciente tiene una medicación estable antes de las seis semanas previas a la inclusión
  • Consentimiento informado firmado

Criterios de exclusión

  • EH juvenil (variante Westphal) o bradicinesia predominante
  • Inestabilidad postural con puntuación de retropulsión UHDRS > 2
  • Comorbilidad grave que comprometa la operabilidad y/o la esperanza de vida y/o la calidad de vida durante la duración del ensayo (por ejemplo, cáncer con esperanza de vida < 6 meses, Niveles 3 y 4 en la clasificación de insuficiencia cardíaca NYHA  que aumenten el riesgo anestésico según el anestesista)
  • Suicidio agudo
  • Psicosis aguda (síntomas en los 6 meses anteriores)
  • Participación en cualquier ensayo clínico de intervención en los 2 meses anteriores al cribado
  • Atrofia cortical de grado 3
  • Pacientes con riesgo de coagulopatías y/o mayor riesgo de hemorragia
  • Pacientes con un marcapasos o desfibrilador implantado
  • Embarazo
  • lactancia

PAÍSES

AUSTRIA

TRIAL SITE:
Medizinische Universität Innsbruck

Address: Innsbruck, Austria, 6020

CONTACT
Klaus Seppi
Tel: + 43 (0)512 504-25810
klaus.seppi@tirol-kliniken.at

Marina Peball
Tel: +43 512 504/82718
marina.peball@tirol-kliniken.at

FRANCIA

TRIAL SITE:
CHU Amiens Hôpital nord, Department of neurosurgery and Department of neurology

Address: Amiens, France, 80054

CONTACT
Pierre Krystkowiak  
Tel.: +33322668240
krystkowiak.pierre@chu-amiens.fr   

Michel Lefranc
Lefranc.Michel@chu-amiens.fr  

TRIAL SITE: 
Hôpital Roger Salengro, Service de Neurologie et Pathologie du mouvement

Address: Lille Cedex, France, 59037

CONTACT

Clemence Simonin
Tel: +33 3.20.44.67.52
clemence.simonin@chru-lille.fr

Eric Decorte
Tel.: +33 03.20.44.59.62
eric.decorte@chru-lille.fr  

ALEMANIA

TRIAL SITE:
kbo-Isar-Amper-Klinikum Taufkirchen

Address: Taufkirchen, Germany, 84416

CONTACT
Michael Bachmaier   
Tel: +49 (0)808 493 4417   
michael.bachmaier@kbo.de

Ralf Marquard
Tel: 08084 934 495
Ralf.Marquard@kbo.de   

TRIAL SITE:
University Hospital Schleswig-Holstein

Address: Kiel, Germany, 24105

CONTACT
Steffen Paschen
Tel: 0431-500-23842    Steffen.Paschen@uksh.de

Birte Hackelberg   
Tel: 0431-597 8519    birte.hackelberg@uksh.de

TRIAL SITE:
Universität zu Lübeck

Address: Lubeck Hansestadt, Germany, 23562

CONTACT
Alexander Münchau
Tel: 0451 31018215    alexander.muenchau@neuro.uni-luebeck.de

Vera Tadic   
Tel: 0451 31018214    vera.tadic@neuro.uni-luebeck.de

TRIAL SITE:
University hospital Munich LMU

Address: Munich, Germany, 80336

CONTACT
Jan Mehrkens
Tel: 08970952698    jan.mehrkens@med.uni-muenchen.de

Kai Bötzel
Tel: 089 7095 3673    Kai.Boetzel@med.uni-muenchen.de

TRIAL SITE:
University Hospital Schleswig-Holstein

Address: Kiel, Germany, 24105

CONTACT
Steffen Paschen
Tel: 0431-500-23842    Steffen.Paschen@uksh.de

Birte Hackelberg   
Tel: 0431-597 8519    birte.hackelberg@uksh.de

 

TRIAL SITE:
University Hospital Freiburg

Address: Freiburg, Germany, 79106

CONTACT

Volker Coenen
Tel: +4976127050630   

volker.coenen@uniklinik-freiburg.de

Eva Maria Wissner

Tel: +49 761 270-50670
eva-maria.wissner@uniklinik-freiburg.de

 

TRIAL SITE:
University hospital Heinrich Heine University Düsseldorf

Address:Düsseldorf, Germany, 40225

CONTACT
Jan Vesper
Tel: +49 211 81 18408    jan.vesper@med.uni-duesseldorf.de

Alfons Schnitzler
Tel: +49 211 81 17893    Schnitza@med.uni-duesseldorf.de

TRIAL SITE:
Charité Campus Virchow Klinikum

Address: Berlin, Germany, 13353

CONTACT
Andrea Kühn
Tel: 030 450 660203    andrea.kuehn@charite.de

Mandy Schickor   
Tel: +49 (0)30 450 660 478    Mandy.Schickor@charite.de

 

SUIZA

TRIAL SITE:
Center for Neurology

Address: Bern, Gümlingen, Switzerland, 3073

CONTACT
Jean Marc Burgunder
Tel: +41 031 352 20 70   
jean-marc.burgunder@dkf.unibe.ch

Michael Schüpbach
Tel: +41 316322168    wmms@bluewin.ch

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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.