The University of Texas Health Science Center at San Antonio
There are no drug treatments for individuals with Congenital Contractures of the Limb and Face, Hypotonia, and Developmental Delay (CLIFAHDD), an ultra-rare and severe neurodevelopmental disease. The investigators have learned more about the cause of the disease and researched possible treatments based on both the cause of the disease and the way certain drugs work. The investigators are interested in understanding the safety of using aprepitant (a drug already approved by the United States Food \& Drug Administration \[FDA\] to treat nausea and vomiting for kids and adults who are receiving chemotherapy) on people diagnosed with CLIFAHDD. The overall goal of this Phase 1 study is to study whether this drug is safe for daily use in individuals with CLIFAHDD and to find more information on how it impacts daily functioning and quality of life. The total study will take around 8 months total. This includes the 90 days before the drug starts and the 21 days after the drug ends.
The sodium leak ion channel NALCN is responsible for a background sodium influx that contributes to the resting membrane potential and serves as a key regulator in neuronal and cell excitability. Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay (CLIFAHDD; OMIM 616266) is a debilitating and ultra-rare neurodevelopmental disease with early infancy onset caused by a de novo autosomal dominant mutation in NALCN, often associated with NALCN gain-of-function (GOF). CLIFAHDD is associated with global neurodevelopmental delay, hyperkinetic movement disorders (e.g., dys…
Inclusion Criteria: 1. Diagnosis of CLIFAHDD (confirmed by clinical and genetic report per best practices) 2. NALCN variant with predicted NALCN gain-of-function in established functional assays and/or computational assessments 3. Age \>6 months at the time of initial consent/assent 4. Weight \>6kg at the time of initial consent/assent 5. Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document. 6. For children (\<18y at time of consent/assent), informed assent (if developmentally appropriate) and parental…
Administration will begin at 1mg/kg up to a maximum of 40mg in weeks 1-4, then escalate to 2mg/kg up to a maximum of 80mg in weeks 5-8, then 3mg/kg up to a maximum of 125mg in weeks 9-12