open label trial of triheptanoin (ux007) in treatment of rett syndrome.

Conditions: Rett Syndrome

Summary: this is a single-center, exploratory, open-label study in 10 girls diagnosed with rett syndrome. the study will consist of the following 4 parts: screening/baseline run-in, titration/dose-setting, treatment, and washout/follow-up.

1. screening and baseline assessments (4 weeks before first treatment): after having the parents sign an informed consent, eligible patients will undergo baseline assessments (safety and disease variables) as follows: * physical examination * vital signs: sitting blood presure (bp),heart rate (hr) and respiratory rate, arm pit temperature. * baseline height and weight parameters * ecg (electrocardiography) * 3-hour video eeg (electroencephalogram) * 24-hour nox-t3 (portable sleep monitor) recording * qol (quality of life) and rett syndrome-specific functional/severity questionnaires * laboratory blood tests, including endocrinology, hematology, and biochemistry. * parents will be requested to fill in a diary and record on a daily basis seizure occurrence for at least 4 weeks before first treatment. in addition they will be asked to record their top 3 concerns pertaining to the care and overall well-being of the patient. 2. treatment period (20 weeks): 1. initial and final dose setting (2 weeks): ux007 will be titrated in each patient over 2 weeks to a dose of 1-4 grams per kilogram per day (based on age). if a subject cannot tolerate titrating up to the 1-4 g/kg/day dose level, the dose should be titrated to the maximum tolerated dose as determined by the investigator. at the end of the titration period, the subject will be maintained on the maximum ux007 dose achieved during the titration period for the duration of the study. the following assessments will be performed: • qol and rtt-specific functional/severity questionnaires 2. final dose (18 weeks): patients will receive a dose of ux007 as determined in the titration/dose setting period. they will be followed up by the investigator and undergo safety and disease-related assessments as follows (schedules outlined in the protocol): * physical examination * vital signs (sitting bp, hr and respiratory rate, oral temperature) * height and weight parameters * ecg * 3-hour video eeg * 24-hour nox recording * motor assessment * qol and rtt-specific functional/severity questionnaires * laboratory blood tests, including endocrinology, hematology, and biochemistry. * data collection from parents' diaries 4. post-washout follow-up/end-of-study: within approximately six (6) weeks after last dose administration, a termination visit will be scheduled. the following activities will take place: * physical examination * vital signs (sitting bp, hr and respiratory rate, oral temperature) * height and weight parameters * ecg * 3-hour video eeg * 24-hour nox recording * motor assessment * qol and rtt-specific functional/severity questionnaires * laboratory blood tests, including endocrinology, hematology, and biochemistry. * data collection from parent's diaries * decision regarding continued administration of ux007 to patients who benefitted from the trial after the dechallenge period

Eligibility criteria:
inclusion criteria: * female patients aged 5 to18 years (inclusive). * a classical diagnosis of rtt, defined according to the internationally agreed 2010 rett search criteria, and with mecp2 pathogenic mutation. * patients with one or both of the following: * at least 2 seizures per month as per history during the four-week baseline period according to parent diary or per 3 hours video eeg recording * walking abilities, independent or with support * patients with breathing abnormalities as recorded by baseline nox recording. exclusion criteria: * patients with significant metabolic, liver, cardiac, or respiratory morbidity not related to rtt * patients with significant liver, cardiac or respiratory morbidity related to rtt

Keywords: rett syndrome, triheptanoic acid, walking, eeg