HEMIHEP: Pilot Study, Comparative, Single-center, Randomized, Crossover, Double-blind, Against Placebo, Testing the Effectiveness of Triheptanoin Oil in Alternating Hemiplegia of Childhood
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Triheptanoin Triheptanoin/ Placebo Randomized to receive active Triheptanoin first for 12 weeks. At cross-over, participants will receive placebo for 12 weeks. Each drug will be dispensed successively. A one-month wash out period is planned for 4 weeks between triheptanoine and placebo phases. |
Drug: Triheptanoin
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.
Other Names:
|
| Placebo Comparator: Placebo Placebo / Triheptanoin Randomized to receive active Placebo first for 12 weeks. At cross-over, participants will receive Triheptanoin for 12 weeks. Each drug will be dispensed successively. A one-month wash out period is planned for 4 weeks between placebo and triheptanoin phases. |
Drug: Placebo
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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
- 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
- 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
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Groupe hospitalier Pitié Salpêtrière | Paris | France | 75013 |
Sponsors and Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
Investigators
- Principal Investigator: Emmanuel Flamand-Roze, MD, PhD, INSERM UMRS 975, 47 bd de l'hôpital - 75651 Paris Cedex 13
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C14-53