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

Primary Purpose

Alternating Hemiplegia of Childhood

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Triheptanoin
Placebo
Sponsored by
Institut National de la Santé Et de la Recherche Médicale, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alternating Hemiplegia of Childhood

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Groupe hospitalier Pitié Salpêtrière

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Triheptanoin

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Clinical Global Impression Scales - Improvement
visit 2 at week 12, visit 4 at week 28
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
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
Clinical Safety as measured by questionnaire
visit 2 at week 12, visit 4 at week 28
Biological Safety as measured by acylcarnitine profile, organic acid dosage
visit 2 at week 12, visit 4 at week 28

Full Information

First Posted
March 24, 2015
Last Updated
February 11, 2020
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT02408354
Brief Title
Pilot Study, Comparative, Single-center, Randomized, Crossover, Double-blind, Against Placebo, Testing the Effectiveness of Triheptanoin Oil in Alternating Hemiplegia of Childhood
Acronym
HEMIHEP
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

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
April 15, 2015 (Actual)
Primary Completion Date
April 5, 2017 (Actual)
Study Completion Date
April 5, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alternating Hemiplegia of Childhood

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Triheptanoin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Triheptanoin
Other Intervention Name(s)
UX007, glycerol triheptanoate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of neurologic paroxystic events report in patient diary
Description
visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28
Time Frame
7 months
Secondary Outcome Measure Information:
Title
Composite score allying the number of neurological paroxystic events, their duration and severity.
Description
visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28
Time Frame
7 months
Title
Clinical Global Impression Scales - Improvement
Description
visit 2 at week 12, visit 4 at week 28
Time Frame
7 months
Title
The Short Form (36) Health Survey
Description
visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28
Time Frame
7 months
Title
Brain 31phosphorus magnetic resonance spectroscopy
Description
Ratio of Inorganic Phosphate (Pi) over Phosphocreatine during visual stimulation visit 2 at week 12, visit 4 at week 28
Time Frame
7 months
Title
Clinical Safety as measured by questionnaire
Description
visit 2 at week 12, visit 4 at week 28
Time Frame
7 months
Title
Biological Safety as measured by acylcarnitine profile, organic acid dosage
Description
visit 2 at week 12, visit 4 at week 28
Time Frame
7 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emmanuel Flamand-Roze, MD, PhD
Organizational Affiliation
INSERM UMRS 975, 47 bd de l'hôpital - 75651 Paris Cedex 13
Official's Role
Principal Investigator
Facility Information:
Facility Name
Groupe hospitalier Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
28969699
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.
Results Reference
derived

Learn more about this trial

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

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