Investigation of the Safety of Intranasal Glulisine in Down Syndrome

A Double-Blind, Placebo-Controlled Pilot Investigation of the Safety of Intranasal Glulisine in Down Syndrome

This study is a single center, randomized, double-blind, placebo-controlled, cross-over pilot study designed to assess the safety of intranasally (IN) delivered glulisine versus placebo in patients with DS. Subjects will be randomized into this cross-over study and within subject comparisons conducted between single treatment of intranasal insulin glulisine and single treatment of intranasal placebo. All subjects will also receive a single treatment of placebo prior to randomization to ensure adherence to study procedures.

Inclusion Criteria:

• Male or female aged 35-80 years with a Down syndrome diagnosis that is confirmed by karyotype.
• Vital signs must be within normal limits for their age. (Medically treated hypertension will be allowed).
• Must have an electrocardiogram free of clinically significant findings.
• Must have an authorized representative to provide written informed consent.
• Level of speech and comprehension of verbal commands are sufficient to understand and to answer simple requests.
• Must have a reliable caregiver or family member who agrees to accompany the subject to all visits, provide information about the subject as required by this protocol.
• Must be independent for activities of daily living.
• Must tolerate the initial IN treatment of placebo and adhere to study procedures.

Exclusion Criteria:

• Any current psychiatric or neurologic diagnosis other than Down syndrome or Down syndrome with dementia that is judged to impact cognition.
• Subjects who currently meet or have within the past five years met DSM-IV (Diagnostic and Statistical Manual) criteria for drug or alcohol abuse or dependence.
• Subjects residing in a skilled nursing facility or subjects who are anticipated to enter a nursing home within the next 6 months. (Subjects may reside in group homes, assisted living, or other residential settings where they do not require 24 hour skilled nursing.)
• Subjects receiving any experimental drug for Down syndrome within the past 30 days of screening visit.
• Subjects with significant allergies to or other significant intolerance insulin.
• Presence of active seizure disorder.
• Presence of significant aggression or agitation that may impact participation with testing and IN administration. All subjects must have NPI-C aggression and agitation subscore ≤ 4 (severity ≤ 2; frequency ≤ 2).
• Significant cerebrovascular disease with Modified Hachinski Score>4.
• Subjects who may not be able to comply with the protocol or perform the outcomes measures due to significant hearing or visual impairment or other issues judged relevant by the investigators.
• Subject has been diagnosed with any form of diabetes mellitus, actively takes insulin, or has HbA1c > 6.1% at screening.