Alternating Hemiplegia of Childhood
Conditions
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.
Interventions
DRUGTriheptanoin
Triheptanoin is a triglyceride composed of three heptanoate (C7 fatty acid) esters. Triheptanoin is manufactured by chemical synthesis from glycerol and heptanoic acid. Triheptanoin is a liquid, intended for oral (PO) administration. Participants will be given approximately 1g/kg of Triheptanoin divided at least in three doses (at 8 am, 12 noon, and 8 pm). A one-day titration period will be used, using 0.5 g/kg increments before arriving at the full dose.
DRUGPlacebo
Placebo is a oily liquid, intended for oral (PO) administration. Participants will be given approximately 1g/kg of Placebo divided at least in three doses (at 8 am, 12 noon, and 8 pm). A one-day titration period will be used, using 0.5 g/kg increments before arriving at the full dose.
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of neurologic paroxystic events report in patient diary | 7 months | visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression Scales - Improvement | 7 months | visit 2 at week 12, visit 4 at week 28 |
| The Short Form (36) Health Survey | 7 months | visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28 |
| Composite score allying the number of neurological paroxystic events, their duration and severity. | 7 months | visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28 |
| Clinical Safety as measured by questionnaire | 7 months | visit 2 at week 12, visit 4 at week 28 |
| Biological Safety as measured by acylcarnitine profile, organic acid dosage | 7 months | visit 2 at week 12, visit 4 at week 28 |
| Brain 31phosphorus magnetic resonance spectroscopy | 7 months | Ratio of Inorganic Phosphate (Pi) over Phosphocreatine during visual stimulation visit 2 at week 12, visit 4 at week 28 |
Countries
France
Outcome results
None listed