- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02408354
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Paris, France, 75013
- Groupe Hospitalier Pitié Salpétrière
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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. |
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:
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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. |
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of neurologic paroxystic events report in patient diary
Time Frame: 7 months
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visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28
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7 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite score allying the number of neurological paroxystic events, their duration and severity.
Time Frame: 7 months
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visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28
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7 months
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Clinical Global Impression Scales - Improvement
Time Frame: 7 months
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visit 2 at week 12, visit 4 at week 28
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7 months
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The Short Form (36) Health Survey
Time Frame: 7 months
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visit 1 at day 0, visit 2 at week 12, visit 3 at week 16, visit 4 at week 28
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7 months
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Brain 31phosphorus magnetic resonance spectroscopy
Time Frame: 7 months
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Ratio of Inorganic Phosphate (Pi) over Phosphocreatine during visual stimulation visit 2 at week 12, visit 4 at week 28
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7 months
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Clinical Safety as measured by questionnaire
Time Frame: 7 months
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visit 2 at week 12, visit 4 at week 28
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7 months
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Biological Safety as measured by acylcarnitine profile, organic acid dosage
Time Frame: 7 months
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visit 2 at week 12, visit 4 at week 28
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7 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Emmanuel Flamand-Roze, MD, PhD, INSERM UMRS 975, 47 bd de l'hôpital - 75651 Paris Cedex 13
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- C14-53
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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