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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 : Active, not recruiting
First Posted : May 25, 2015
Last Update Posted : July 15, 2019
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Tracking Information
First Submitted Date  ICMJE May 12, 2015
First Posted Date  ICMJE May 25, 2015
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE June 29, 2015
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
  • 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
  • volumetric magnetic resonance imaging [ Time Frame: 6 months ]
    A decrease in the rate of caudate atrophy, using volumetric MRI
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02453061 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
  • 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
  • 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
  • Patient autonomy after 6 months [ Time Frame: 6 months ]
    Stability of the Total Functional Capacity (TFC) after 6 months of treatment
  • Patient autonomy after 12 months [ Time Frame: 12 months ]
    Stability of the Total Functional Capacity (TFC) after 12 months of treatment
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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).
  • 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
  • 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
  • Number of adverse events [ Time Frame: 12 months ]
    Safety of triheptanoin will be evaluated based on review of adverse events
  • clinical exam for Long term tolerance [ Time Frame: 12 months ]
    Long-term tolerance will be confirmed by clinical exam at study visits
  • home nurse visits for Long term tolerance [ Time Frame: 12 months ]
    Long-term tolerance will be confirmed by patient report during home nurse visits
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
Official Title  ICMJE A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Huntington Disease
Intervention  ICMJE
  • Drug: Triheptanoin oil
    Triheptanoin oil orally administered at 1g/kg/day
  • Drug: Placebo
    Safflower oil orally administered at 1g/kg/day
Study Arms  ICMJE
  • 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)
    Intervention: Drug: Placebo
  • 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)
    Intervention: Drug: Triheptanoin oil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 20, 2015)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02453061
Other Study ID Numbers  ICMJE C14-62
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institut National de la Santé Et de la Recherche Médicale, France
Study Sponsor  ICMJE Institut National de la Santé Et de la Recherche Médicale, France
Collaborators  ICMJE Ultragenyx Pharmaceutical Inc
Investigators  ICMJE Not Provided
PRS Account Institut National de la Santé Et de la Recherche Médicale, France
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP