Sodium Oxybate in Patients With Alternating Hemiplegia of Childhood (AHC-SO)

Phase 1

Completed

Conditions: Alternating Hemiplegia of Childhood

Interventions: Drug: Sodium Oxybate

Registration Number: NCT00931164

Lead Sponsor: University of Utah

Brief Summary: WHO: The investigators are recruiting children and young adults to participate in a research study who:

1. Have been diagnosed with Alternating Hemiplegia of Childhood (AHC)

2. Are between the ages of 6 months - 25 years old

3. Have at least three 10-minute-long AHC episodes during a typical week

4. Can commit to 12 weeks of completing of a daily log describing AHC episodes and to a multi-night hospital stay at the University of Utah Center for Clinical and Translational Science (CCTS)

WHY: The goal of this study is to evaluate whether the study drug can safely and effectively decrease AHC episodes and improve the quality of life of individuals with AHC.

WHAT and WHERE: This study involves at least 12 weeks of completing and submitting daily AHC Episode Logs and a five-day hospital stay at the University of Utah CCTS.

There are 4 phases of the study, and they include:

1. Six weeks of daily log completion prior to starting study drug

2. Five day stay at the University of Utah CCTS

3. Six additional weeks of daily log completion while using study drug at home

4. One day clinic visit to the University of Utah for follow up

COMPENSATION:

There is no fee to participate. All procedures performed specifically for this study will be covered by the study and will not be billed to you or your insurance company.

The study drug will be dispensed to you free of charge. Meals and lodging at the study site will be provided free of charge for the study participant and one care provider. Additionally, the research team will assist subjects with booking and obtaining free transportation, such as an airline tickets, to and from the study site.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Subjects must meet all of the following inclusion criteria.

AHC classic criteria:
- Onset of symptomatology prior to 18 months of age
- Repeated attacks of hemiplegia involving either side of the body
- Paroxysmal disturbances, including tonic or dystonic spells, oculomotor abnormalities, and various autonomic phenomena, during hemiplegic bouts or in isolation
- Episodes of bilateral hemiplegia or quadriplegia starting either as generalization of a hemiplegic episode or bilateral from the beginning
- Immediate disappearance of symptoms upon sleeping, with possible resumption 10-20 minutes after waking
- Evidence of developmental delay and neurologic abnormalities including choreoathetosis, dystonia, or ataxia

In addition:

Provision of a complete daily event log for 6 weeks prior to initiation of sodium oxybate therapy, including the: (1) frequency, (2) duration, (3) type, (4) severity of episodes, and (5) therapies, if any, used in an attempt to abort the episode
Ages 6 months to 25 years at the time of study enrollment
Minimum of 3 AHC episodes weekly, lasting at least 10 minutes each, on average prior to study enrollment
Brain neuroimaging studies excluding alternative etiology for symptoms
Documented absence of epileptiform features on EEG during typical ictal events
Ability of primary caregivers of study participants to submit online daily AHC Episode Logs indicating frequency and duration of ictal episodes over the entire study period
Written informed consent from parents/guardians and assent from children 7 years or older
Girls/women > 12 years of age will be required to be on birth control continuously if they are considered at risk to become pregnant. Those not on birth control will be required to have a screening pregnancy test at baseline, and to confirm their willingness to practice birth control or abstain from sexual activity for the duration of treatment with study medication.

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from participation.

History of hepatic insufficiency, renal insufficiency, significant respiratory disease, cardiac arrhythmia, congenital heart defect, hypertension, or ischemic stroke
History of allergy/sensitivity to sodium oxybate
Use of sodium oxybate within 30 days of study enrollment
Serious illness requiring systemic treatment and/or hospitalization within two weeks prior to study enrollment
Change in neurologic medication regimen within 30 days of study enrollment.
Inability to stay at the Center for Clinical and Translational Science (CCTS) for 5 days due to behavioral issues
Unwillingness or inability to travel to study site during the necessary 1 week titration period to determine the most appropriate dose of GHB for subsequent administration
Noncompliance with AHC Episode Log or study visit requirements
Sleep apnea not adequately treated with C-PAP and oxygen saturation monitoring prior to drug therapy initiation
Succinic semialdehyde dehydrogenase deficiency

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sodium oxybate	Sodium Oxybate	* The study is an open-label, Phase I/II trial designed to obtain additional safety and pharmacokinetic parameters for use of sodium oxybate in children and adolescents afflicted with AHC. * Given the limited number of children carrying the diagnosis of AHC, typical controls will not be available for our study. In lieu of this, the subjective recording of ictal episodes in the 6 week period prior to drug initiation will serve as reference in determining drug efficacy.

Primary Outcome Measures

Name	Time	Method
Time Duration of AHC Episodes	Week 7
Observed Safety Data During 5-day Hospitalization for Drug Dose Identification	Week 7
Number of Participants Who Reported Side Effects During Home Drug Maintenance Phase	1 year

Secondary Outcome Measures

Name	Time	Method
Mean Daily Percentage of Time That Functional Status is Affected Due to Episodes	Week 14
Quality of Life Questionnaires	Week 14
Mood and Behavior Questionnaires	Week 14
Functional Skills Questionnaires	Week 14
Neuropsychological Tests	Week 14