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

Huntington Disease Clinical Trial

— TRIHEP3  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02453061
• Other study ID #: C14-62
• Status: Completed
• Phase: Phase 2
• Start date: June 29, 2015
• Est. completion date: December 3, 2019

Study information

• Verified date: August 2021
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 3, 2019
• Est. primary completion date: December 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease

Intervention

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

Locations

Country	Name	City	State
France	Département de Génétique	Paris
Netherlands	Department of Neurology	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France	Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	31-Phosphorus Magnetic Resonance Spectroscopy	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	3 months
Primary	volumetric magnetic resonance imaging	A decrease in the rate of caudate atrophy, using volumetric MRI	6 months
Secondary	motor function after 6 months	Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 6 months of treatment	6 months
Secondary	motor function after 12 months	Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 12 months of treatment	12 months
Secondary	Patient autonomy after 6 months	Stability of the Total Functional Capacity (TFC) after 6 months of treatment	6 months
Secondary	Patient autonomy after 12 months	Stability of the Total Functional Capacity (TFC) after 12 months of treatment	12 months
Secondary	Sustained restoration of brain energy metabolism after 6 months	Sustained restoration of brain energy metabolism using 31P-MRS after 6 months of treatment	6 months
Secondary	Sustained restoration of brain energy metabolism after 12 months	Sustained restoration of brain energy metabolism using 31P-MRS after 12 months of treatment	12 months
Secondary	Symbol Digit Modalities Test after 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	6 months
Secondary	Symbol Digit Modalities Test after 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	12 months
Secondary	Stroop test after 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	6 months
Secondary	Stroop test after 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	12 months
Secondary	Trail making test after 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	6 months
Secondary	Trail making test after 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	12 months
Secondary	Digit span test after 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	6 months
Secondary	Digit span test after 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	12 months
Secondary	psychiatric symptoms after 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	3 months
Secondary	psychiatric symptoms after 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	6 months
Secondary	psychiatric symptoms after 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	9 months
Secondary	psychiatric symptoms after 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	12 months
Secondary	patients' daily life	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).	6 months
Secondary	quality of life questionnaire after 6 months	A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 6 months	6 months
Secondary	quality of life questionnaire after 12 months	A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 12 months	12 months
Secondary	Number of adverse events	Safety of triheptanoin will be evaluated based on review of adverse events	12 months
Secondary	clinical exam for Long term tolerance	Long-term tolerance will be confirmed by clinical exam at study visits	12 months
Secondary	home nurse visits for Long term tolerance	Long-term tolerance will be confirmed by patient report during home nurse visits	12 months