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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)

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ClinicalTrials.gov Identifier: NCT02408354
Recruitment Status : Unknown
Verified March 2017 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was:  Active, not recruiting
First Posted : April 3, 2015
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

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
Alternating Hemiplegia of Childhood Drug: Triheptanoin Drug: Placebo 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : March 2015
Estimated Primary Completion Date : March 2017
Estimated Study Completion Date : December 2017


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.




Primary Outcome Measures :
  1. Number of neurologic paroxystic events report in patient diary [ Time Frame: 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 :
  1. Composite score allying the number of neurological paroxystic events, their duration and severity. [ Time Frame: 7 months ]
    visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28

  2. Clinical Global Impression Scales - Improvement [ Time Frame: 7 months ]
    visit 2 at week 12, visit 4 at week 28

  3. The Short Form (36) Health Survey [ Time Frame: 7 months ]
    visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28

  4. Brain 31phosphorus magnetic resonance spectroscopy [ Time Frame: 7 months ]
    Ratio of Inorganic Phosphate (Pi) over Phosphocreatine during visual stimulation visit 2 at week 12, visit 4 at week 28

  5. Clinical Safety as measured by questionnaire [ Time Frame: 7 months ]
    visit 2 at week 12, visit 4 at week 28

  6. Biological Safety as measured by acylcarnitine profile, organic acid dosage [ Time Frame: 7 months ]
    visit 2 at week 12, visit 4 at week 28



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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02408354


Locations
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France
Groupe hospitalier Pitié Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
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Principal Investigator: Emmanuel Flamand-Roze, MD, PhD INSERM UMRS 975, 47 bd de l'hôpital - 75651 Paris Cedex 13

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02408354     History of Changes
Other Study ID Numbers: C14-53
First Posted: April 3, 2015    Key Record Dates
Last Update Posted: March 7, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
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Hemiplegia
Paralysis
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Glycerol
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs