Intervention: Sodium Oxybate
Trial phase: Phase 1 | Phase 2
ATC code: B05XA02 | N01AX11 | N07XX04
SMILES: O=C([O-])CCCO.[Na+]
Sex: All
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 6
Group description: 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.

Sodium Oxybate : dosage is by weight
Eligibility criteria:
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