Pilot Study, Comparative, Single-center, Randomized, Crossover, Double-blind, Against Placebo, Testing the Effectiveness of Triheptanoin Oil in Alternating Hemiplegia of Childhood (HEMIHEP)

"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

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.

Study Overview

• Status: Completed
• Conditions: Alternating Hemiplegia of Childhood
• Intervention / Treatment: Drug: Triheptanoin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Groupe Hospitalier Pitié Salpétrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: UX007; glycerol triheptanoate
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of neurologic paroxystic events report in patient diary	visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite score allying the number of neurological paroxystic events, their duration and severity.	visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28	7 months
Clinical Global Impression Scales - Improvement	visit 2 at week 12, visit 4 at week 28	7 months
The Short Form (36) Health Survey	visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28	7 months
Brain 31phosphorus magnetic resonance spectroscopy	Ratio of Inorganic Phosphate (Pi) over Phosphocreatine during visual stimulation visit 2 at week 12, visit 4 at week 28	7 months
Clinical Safety as measured by questionnaire	visit 2 at week 12, visit 4 at week 28	7 months
Biological Safety as measured by acylcarnitine profile, organic acid dosage	visit 2 at week 12, visit 4 at week 28	7 months

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2015
• Primary Completion (Actual): April 5, 2017
• Study Completion (Actual): April 5, 2017

Study Registration Dates

• First Submitted: March 24, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Paralysis; Hemiplegia; Physiological Effects of Drugs; Protective Agents; Cryoprotective Agents; Glycerol
• Other Study ID Numbers: C14-53