low-dose ketamine in children with adnp syndrome

Conditions: ADNP Syndrome

Summary: this is a phase 2a, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "iv") of ketamine in children with adnp syndrome (activity-dependent neuroprotective protein). the study team will enroll 10 participants, ages 5 to 12, at mount sinai. the study participation is expected to last 4 weeks and will include 5 scheduled clinic visits in order to complete safety monitoring, clinical assessments, and biomarker collection. at the conclusion of this study, the study team expects to demonstrate the safety and tolerability of low-dose ketamine in children with adnp syndrome. additionally, the study team anticipates identifying meaningful signals of efficacy in clinical outcome measures using rna and dna sequencing to analyze adnp protein expression and dna methylation profiles, a natural process by which methyl groups are added to the dna to change its activity, in order to assess sensitivity to change with low-dose ketamine treatment and inform future phase 3 studies. ketamine is not currently approved by the food and drug administration to treat this syndrome, but it is approved for use in children in other situations, for example in anesthesia.


Eligibility criteria:
inclusion criteria: * 5 to 12 years old (inclusive) at the time of informed consent; * has a diagnosis of adnp syndrome, confirmed by genetic testing prior to subject randomization; * has a clinical global impression-severity score of 4 (moderately ill) or greater at screening; * any concomitant medication, including anti-epileptic and/or behavioral medications, supplements, and special diets, must be at a stable dose for at least 4 weeks before; * has an english-speaking caregiver capable of providing informed consent and able to attend all scheduled study visits, oversee the administration of study drug, and provide feedback regarding the subject's behavior and other symptoms as described in the protocol; * provide assent to the protocol (when applicable); * has a caregiver who will agree not to post any of the subject's personal medical data related to the study or information related to the study on any website or social media site (e.g., facebook and twitter) until they have been notified that the study is completed. * age-specific blood pressure parameters for inclusion in the study will be based on established guidelines. exclusion criteria: * has a concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or any clinically significant finding at screening that could interfere with the conduct of the study or that would pose an unacceptable risk to the subject in this study; * has clinically significant lab abnormalities or vital signs at the time of screening (e.g., alanine aminotransferase or aspartate aminotransferase \>2.5 × upper limit of normal; total bilirubin or creatinine \>1.5 × upper limit of normal). re-testing of safety labs is allowed; * hypertension that is not well controlled (systolic bp \>130-140 mm hg or diastolic bp \>85-95 mm hg depending on age); * a blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits; * thyroid impairment, as reflected by a tsh \> 4.2 mu/l; * cardiac disease, as reflected by an ekg that is abnormal and of concern for cardiac disease; * has had changes in his/her medication regimen within the previous month; * has a history of uncontrollable seizure disorder or seizure episodes within 1 month of screening; * has a history of suicidal behavior or considered by the investigator to be at high risk of suicide; * has a current or past history of psychotic symptoms; * has enrolled in any clinical trial or used of any investigational agent, device, and/or investigational procedure within the 30 days before screening or does so concurrently with this study.

Keywords: ketamine adnp activity-dependent neuroprotector protein chromosome disorders chromosome aberrations