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A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease (TRIHEP3)

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ClinicalTrials.gov Identifier: NCT02453061
Recruitment Status : Recruiting
First Posted : May 25, 2015
Last Update Posted : March 9, 2017
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Brief Summary:
In the study the investigators plan to include 100 early affected HD patients (5 ≤ UHDRS ≤ 40) in a randomized, double-blind, controlled study in 2 centers (France and the Netherlands). Patients will receive either triheptanoin at 1g/kg of body weight per day (n = 50), or a control oil (n = 50) at 1g/kg of body weight per day for 6 months followed by an open label phase using triheptanoin for another 6 months. Efficacy of triheptanoin will be evaluated by measurements of caudate volume using volumetric magnetic resonance imaging and brain energy metabolism as evaluated by the ratio of inorganic phosphate/phosphocreatine, during visual stimulation, using 31P-MRS. Clinical improvement will be evaluated by UHDRS, TFC, and PBA-S scores as well as performance on the neuropsychological battery; patient quality of life will be evaluated with qualitative research methods after 6 months and with the SF-36 questionnaire before and after treatment; biological tolerance and compliance will be evaluated by routine biochemical blood tests, plasma and urine measurements of triheptanoin oil derivatives and patient report.

Condition or disease Intervention/treatment Phase
Huntington Disease Drug: Triheptanoin oil Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
Study Start Date : June 2015
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo group
Subjects will receive safflower oil at 1g/kg/day for 6 months (months 0 - 6) and triheptanoin oil at 1g/kg/day for 6 months (months 7 - 12)
Drug: Placebo
Safflower oil orally administered at 1g/kg/day

Active Comparator: Triheptanoin group
Subjects will receive triheptanoin oil at 1g/kg/day for 6 months (months 0 - 6) and triheptanoin oil at 1g/kg/day for 6 months (months 7 - 12)
Drug: Triheptanoin oil
Triheptanoin oil orally administered at 1g/kg/day




Primary Outcome Measures :
  1. 31-Phosphorus Magnetic Resonance Spectroscopy [ Time Frame: 3 months ]
    An increase in the index of brain energy restoration - as defined by the difference between Pi/PCr ratio during visual stimulation and the mean of Pi/PCr ratio during rest and recovery - using 31P-MRS

  2. volumetric magnetic resonance imaging [ Time Frame: 6 months ]
    A decrease in the rate of caudate atrophy, using volumetric MRI


Secondary Outcome Measures :
  1. motor function after 6 months [ Time Frame: 6 months ]
    Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 6 months of treatment

  2. motor function after 12 months [ Time Frame: 12 months ]
    Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 12 months of treatment

  3. Patient autonomy after 6 months [ Time Frame: 6 months ]
    Stability of the Total Functional Capacity (TFC) after 6 months of treatment

  4. Patient autonomy after 12 months [ Time Frame: 12 months ]
    Stability of the Total Functional Capacity (TFC) after 12 months of treatment

  5. Sustained restoration of brain energy metabolism after 6 months [ Time Frame: 6 months ]
    Sustained restoration of brain energy metabolism using 31P-MRS after 6 months of treatment

  6. Sustained restoration of brain energy metabolism after 12 months [ Time Frame: 12 months ]
    Sustained restoration of brain energy metabolism using 31P-MRS after 12 months of treatment

  7. Symbol Digit Modalities Test after 6 months [ Time Frame: 6 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the SDMT (Symbol Digit Modalities Test), a test of visuomotor coordination

  8. Symbol Digit Modalities Test after 12 months [ Time Frame: 12 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the SDMT (Symbol Digit Modalities Test), a test of visuomotor coordination

  9. Stroop test after 6 months [ Time Frame: 6 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the Stroop test, a test evaluating concentration and capacity for inhibition

  10. Stroop test after 12 months [ Time Frame: 12 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the Stroop test, a test evaluating concentration and capacity for inhibition

  11. Trail making test after 6 months [ Time Frame: 6 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the Trail making test, a test to evaluate mental flexibility

  12. Trail making test after 12 months [ Time Frame: 12 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the Trail making test, a test to evaluate mental flexibility

  13. Digit span test after 6 months [ Time Frame: 6 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the Digit span test, a test evaluating attention and working memory

  14. Digit span test after 12 months [ Time Frame: 12 months ]
    The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the Digit span test, a test evaluating attention and working memory

  15. psychiatric symptoms after 3 months [ Time Frame: 3 months ]
    The effect of triheptanoin on psychiatric symptoms will be evaluated after 3 months with the PBA-S, an evaluation of problem behaviors associated with HD

  16. psychiatric symptoms after 6 months [ Time Frame: 6 months ]
    The effect of triheptanoin on psychiatric symptoms will be evaluated after 6 months with the PBA-S, an evaluation of problem behaviors associated with HD

  17. psychiatric symptoms after 9 months [ Time Frame: 9 months ]
    The effect of triheptanoin on psychiatric symptoms will be evaluated after 9 months with the PBA-S, an evaluation of problem behaviors associated with HD

  18. psychiatric symptoms after 12 months [ Time Frame: 12 months ]
    The effect of triheptanoin on psychiatric symptoms will be evaluated after 12 months with the PBA-S, an evaluation of problem behaviors associated with HD

  19. patients' daily life [ Time Frame: 6 months ]
    The global impact of triheptanoin on patients' daily life will be evaluated at the end of the blinded treatment period using qualitative research methods. To statistically test whether experts classify treated and not treated patients better than could be expected by chance, a permutation test based on a modified version of Fisher's Lady tasting tea procedure will be used (Fischer 1935).

  20. quality of life questionnaire after 6 months [ Time Frame: 6 months ]
    A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 6 months

  21. quality of life questionnaire after 12 months [ Time Frame: 12 months ]
    A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 12 months

  22. Number of adverse events [ Time Frame: 12 months ]
    Safety of triheptanoin will be evaluated based on review of adverse events

  23. clinical exam for Long term tolerance [ Time Frame: 12 months ]
    Long-term tolerance will be confirmed by clinical exam at study visits

  24. home nurse visits for Long term tolerance [ Time Frame: 12 months ]
    Long-term tolerance will be confirmed by patient report during home nurse visits



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02453061


Contacts
Contact: Fany Mochel +331 42 16 13 46 fanny.mochel@upmc.fr
Contact: Alexandra Durr +331 57 27 46 82 alexandra.durr@upmc.fr

Locations
France
Département de Génétique Recruiting
Paris, France, 75013
Contact: Fanny MOCHEL    +331 42 16 13 46    fanny.mochel@upmc.fr   
Contact: Alexandra Durr    +331 57 27 46 82    alexandra.durr@upmc.fr   
Netherlands
Department of Neurology Not yet recruiting
Leiden The Netherlands, Netherlands, 2300RC
Contact: Raymund Roos       R.A.C.Roos@lumc.nl   
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Ultragenyx Pharmaceutical Inc

Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02453061     History of Changes
Other Study ID Numbers: C14-62
First Posted: May 25, 2015    Key Record Dates
Last Update Posted: March 9, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders