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

• ClinicalTrials.gov Identifier: NCT02453061
• Recruitment Status: Completed
• First Posted: May 25, 2015
• Last Update Posted: August 25, 2021
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• 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: May 12, 2015
• First Posted Date: May 25, 2015
• Last Update Posted Date: August 25, 2021
• Actual Study Start Date: June 29, 2015
• Actual Primary Completion Date: December 3, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Huntington Disease

Intervention

• Drug: Triheptanoin oil
  Triheptanoin oil orally administered at 1g/kg/day
• Drug: Placebo
  Safflower oil orally administered at 1g/kg/day

Study Arms

• 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 *: Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 20, 2015): 100
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 3, 2019
• Actual Primary Completion Date: December 3, 2019 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Netherlands

Administrative Information

• NCT Number: NCT02453061
• Other Study ID Numbers: C14-62
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• Original Responsible Party: Same as current
• Current Study Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Original Study Sponsor: Same as current
• Collaborators: Ultragenyx Pharmaceutical Inc
• Investigators: Not Provided
• PRS Account: Institut National de la Santé Et de la Recherche Médicale, France
• Verification Date: August 2021