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

NCT02453061 | Completed Phase 2

• 1 other identifier: C14-62
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 2

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. Clinical improvement will be evaluated by brain energy metabolism quantification as evaluated by the ratio of inorganic phosphate/phosphocreatine, during visual stimulation, using 31P-MRS, UHDRS, TFC, and PBA-S scores as well as performance on the neuropsychological battery. Patient quality of life will be evaluated 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.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (1)

• volumetric magnetic resonance imaging

  A decrease in the rate of caudate atrophy, using volumetric MRI

  6 months

Secondary Outcomes (26)

• motor function after 6 months

  6 months

• 31- Phosphorus Magnetic Resonance Spectroscopy

  3 months

• Caudal Atrophy

  12 months

• motor function after 12 months

  12 months

• Patient autonomy after 6 months

  6 months

Study Arms (2)

Placebo group

PLACEBO COMPARATOR

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

Triheptanoin group

ACTIVE COMPARATOR

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

Interventions

Triheptanoin oil DRUG

Triheptanoin oil orally administered at 1g/kg/day

Triheptanoin group

Placebo DRUG

Safflower oil orally administered at 1g/kg/day

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Hypersensitivity to triheptanoin or to one of its excipients
• Additional major comorbidities
• History of severe head injury
• 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

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (2)

Département de Génétique

Paris, 75013, France

Location

Department of Neurology

Leiden, 2300RC, Netherlands

Location

Related Publications (2)

• Mochel F, Meneret A, Adanyeguh IM, Giron C, Hainque E, Luton MP, Atencio M, Debs R, Jacobs M, Veldkamp FCM, Barbier M, Coppen EM, van der Zwaan KF, Diallo A, Ottolenghi C, Vicaut E, Roos RA, Durr A. Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study. Neurology. 2025 Jan 28;104(2):e210194. doi: 10.1212/WNL.0000000000210194. Epub 2024 Dec 30.

  PMID: 39804569 DERIVED

• 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.

  PMID: 31381524 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

triheptanoin

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 25, 2015
• Study Start: June 29, 2015
• Primary Completion: December 3, 2019
• Study Completion: December 3, 2019
• Last Updated: July 15, 2024

Record last verified: 2024-07

Locations

FR (1); NL (1)