Clinical trial NCT02408354: Pilot Study, Comparative, Single-center, Randomized, Crossover, Double-blind, Against Placebo, Testing the Effectiveness of Triheptanoin Oil in Alternating Hemiplegia of Childhood
Official title: "Etude Pilote, Comparative, Monocentrique, randomisée, en Cross Over, en Double Aveugle, Contre Placebo, Testant l'efficacité de l'Huile triheptanoïne Dans Les Hémiplégies Alternantes de l'Enfant" HEMIHEP
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alternating Hemiplegia of Childhood
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2015-04-03
Enrollment: 10
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this project is to study the efficacy of triheptanoin oil in patients with Alternating Hemiplegia of Childhood (AHC) due to ATP1A3 gene mutation.

Detailed description: The clinical spectrum of Alternating Hemiplegia of Childhood (AHC) is wide and characterized by the association of permanent and paroxysmal (palsy, dystonia, ocular, epileptic, dysautonomic events) neurological events, with onset in childhood. Most of AHC patients carry mutations in the ATP1A3 gene. This gene encodes the Na+/K+ ATPase witch is a transmembrane ion pump generating chemical and electrical gradient of sodium and potassium across the plasma membrane. Those paroxystic events in AHC patients with mutations in the ATP1A3 gene could be associated with a glucidic/energetic metabolism or intracerebral excitability disorder.

Triheptanoin is a triglyceride, whose derivatives pass the blood - brain barrier and enhance the Krebs cycle functions. Triheptanoin could therefore allow energy supply to the brain, which is essential for the functioning of the Na+/ K+ ATPase that consumes a significant amount of energy in the brain.

The investigators goal is to do a pilot study to test the effectiveness on paroxystic manifestations and the safety of triheptanoin in a small group of patients with Alternating Hemiplegia of Childhood secondary to ATP1A3 mutations.

Eligibility criteria: Inclusion Criteria:

* AHC with mutation in ATP1A3 gene
* Age ≥ 15 years and 3 months
* ≥ 6 neurological paroxystic events during the last 3 months prior to the beginning of the study
* No specific diet
* Covered by french social security
* Patients who freely agree to participate in this study and understand the nature, risks and benefits of this study and give their written informed consent. (In addition to the requirement for the consent of parents or the legal representative, adolescents can provide additional informed consent to participate in clinical trials)

Exclusion Criteria:

* Age \< 15 years and 3 months
* Evidence of psychiatric disorder
* Comorbid medical condition that would render them unsuitable for the study, e.g. HIV, diabetes
* Pregnant or parturient or lactating women
* Absence of double effective contraception at the women old enough to procreate
* Unwillingness to be informed in case of abnormal MRI
* Absence of signed informed consent
* No covered by french social security
* Persons deprived of their liberty by judicial or administrative decision
* Person subject to an exclusion period for another research
* Subjects with exclusion criteria required by french law

Primary outcomes:
measure: Number of neurologic paroxystic events report in patient diary
timeFrame: 7 months
Secondary outcomes:
measure: Composite score allying the number of neurological paroxystic events, their duration and severity.
timeFrame: 7 months
measure: Clinical Global Impression Scales - Improvement
timeFrame: 7 months
measure: The Short Form (36) Health Survey
timeFrame: 7 months
measure: Brain 31phosphorus magnetic resonance spectroscopy
timeFrame: 7 months
measure: Clinical Safety as measured by questionnaire
timeFrame: 7 months
measure: Biological Safety as measured by acylcarnitine profile, organic acid dosage
timeFrame: 7 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe hospitalier Pitié Salpêtrière
Study officials:
affiliation: INSERM UMRS 975, 47 bd de l'hôpital - 75651 Paris Cedex 13
name: Emmanuel Flamand-Roze, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hainque E, Caillet S, Leroy S, Flamand-Roze C, Adanyeguh I, Charbonnier-Beaupel F, Retail M, Le Toullec B, Atencio M, Rivaud-Pechoux S, Brochard V, Habarou F, Ottolenghi C, Cormier F, Meneret A, Ruiz M, Doulazmi M, Roubergue A, Corvol JC, Vidailhet M, Mochel F, Roze E. A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood. Orphanet J Rare Dis. 2017 Oct 2;12(1):160. doi: 10.1186/s13023-017-0713-2.