Clinical trial NCT02432716: Investigation of the Safety of Intranasal Glulisine in Down Syndrome
Official title: A Double-Blind, Placebo-Controlled Pilot Investigation of the Safety of Intranasal Glulisine in Down Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Down Syndrome
Lead sponsor: HealthPartners Institute
Sponsor class: OTHER
First posted: 2015-05-04
Enrollment: 12
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety Measured by Adverse Events
timeFrame: 1 year
Secondary outcomes:
measure: Cognitive Change Measured by Fuld Object-Memory Evaluation (FOME)
timeFrame: 20 minutes
measure: Memory Retention Measured by Fuld Object-Memory Evaluation (FOME)
timeFrame: 20 minutes
measure: Cognitive Change Measured by Rivermead Behavioral Memory Test (RBMT-C)
timeFrame: 20 minutes
measure: Memory Retention Measured by Rivermead Behavioral Memory Test (RBMT-C).
timeFrame: 20 minutes
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: HealthPartners Neuroscience Center
state: Minnesota
Study officials:
affiliation: HealthPartners Institute
name: Michael H Rosenbloom, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosenbloom M, Barclay T, Johnsen J, Erickson L, Svitak A, Pyle M, Frey W, Hanson LR. Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome. Drugs R D. 2020 Mar;20(1):11-15. doi: 10.1007/s40268-020-00296-2.