TRIHEP3

A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington’s Disease

Completed

ABOUT

SPONSOR

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

PARTICIPANTS

100

In this trial a compound called Triheptanoin is tested to see if it has a positive impact on HD patients functions in all areas but with a special emphasis on cognitive functions. Trhiheptanoion is artificially produced and it is a fat. It is almost tasteless and colorless and is already used as medical food to treat certain diseases related to the bodies energy production, socalled metabolic disorders. We know that the brain cells energy production is negatively affected in HD. 100 participants is included in the trial. 50 will get Triheptanoin each day for 12 months. The other 50 participants will for the first 6 months receive placebo. But for the following 6 months they will get Trheptanoin. Potential effect will be tested with MRS to get an image of whether the energy production has improved or at least not decreased. MRI images will also be taken to see any effect on brain volume. In addition the participants will be tested with a battery of motor and cognitive tests as well as questionnaires related to general function and psychiatric status.

Estimated Study Completion Date: 31 December, 2020

Ages Eligible for Study:

18 Years and older (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Inclusion Criteria

  • Positive genetic test with CAG repeat length ≥39 in HTT gene
  • At least 18 years of age
  • Signature of informed consent
  • Covered by social security
  • UHDRS score between 5 and 40
  • Ability to undergo MRI scanning
  • BMI between 18 and 30

Exclusion Criteria

  • Hypersensitivity to triheptanoin or to one of its excipients
  • Additional major comorbidities
  • History of severe head injury
  • Participation in another therapeutic trial (3 month exclusion period)
  • For women of childbearing age, the absence of two forms of effective contraception (with the exception of those who are abstinent)
  • Pregnancy or breastfeeding
  • Inability to understand information about the protocol
  • Persons deprived of their liberty by judicial or administrative decision
  • Adult subject under legal protection or unable to consent
  • Treatment with tetrabenazine

COUNTRIES

FRANCE

TRIAL SITE:
Département de Génétique
Address:Paris, France

NETHERLANDS

TRIAL SITE:
Department of Neurology
Address: Leiden, Netherlands

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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.