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Investigation of the Safety of Intranasal Glulisine in Down Syndrome

Primary Purpose

Down Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Insulin glulisine
Saline
Sponsored by
HealthPartners Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Down Syndrome

Eligibility Criteria

35 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • HealthPartners Neuroscience Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Insulin (glulisine), then Placebo

Placebo, then Insulin (glulisine)

Arm Description

Participants first receive one dose of Glulisine 20 IU/IN (.1ml/10 units intranasal in each nostril). After a washout period of 2 weeks, they then received one dose of placebo, Sterile Normal Saline 20 IU/IN (.1ml intransal in each nostril).

Participants first receive one dose of placebo, Sterile Normal Saline 20 IU/IN (.1ml intransal in each nostril). After a washout period of 2 weeks, they then received one dose of Glulisine 20 IU/IN (.1ml/10 units intranasal in each nostril).

Outcomes

Primary Outcome Measures

Safety Measured by Adverse Events
Number of adverse and/or serious events

Secondary Outcome Measures

Cognitive Change Measured by Fuld Object-Memory Evaluation (FOME)
During the examination, a patient is presented with ten common objects they are asked to identify by touch. The test uses distraction to test recall. For all, a higher score indicates a better outcome. Learning curve is the number of objects the difference in the number of items they are able to correctly identify from the greater of trials 4 or 5 compared to trial 1. Range: 0-10 Total immediate recall is the number of objects recalled over all of the trials. Range: 0-50 Total delayed recall is the number of objects recalled after 5 minutes. Range: 0-10 Recognition memory is the number of items correct from a multiple choice list of three when unable to correctly identify items from delayed recall. Range: 0-10 Retention estimate is the number of items recalled after 5 minutes or being reminded with multiple choice. Range: 0-10
Memory Retention Measured by Fuld Object-Memory Evaluation (FOME)
Memory retention is the percentage of items correctly identify during the delayed recall trial compared storage trial 5. Range: 0-100 percent. A higher percentage indicates a better outcome.
Cognitive Change Measured by Rivermead Behavioral Memory Test (RBMT-C)
The RBMT-C provides an objective measure of everyday memory problems reported and observed in subjects with memory difficulties. The test is standardized for use with children ranging in age from 5 to 10 years. Here, we used it for evaluation of Down Syndrome subjects. The story recall subtests involves immediate free recall, cued recall, and delayed recall of short story material which is presented orally to subjects by the examiner. The RBMT-C is appealing for use in this population because the task is engaging, simple, and has been shown in other studies to be an effective measure of memory functions. For all, a higher score means a better outcome. Immediate Recall is the number of story elements recalled right after the story is complete. Range: 0-31 Delayed Recall is the number of story elements recalled after a delay. Range: 0-31
Memory Retention Measured by Rivermead Behavioral Memory Test (RBMT-C).
The RBMT-C provides an objective measure of everyday memory problems reported and observed in subjects with memory difficulties. The test is standardized for use with children ranging in age from 5 to 10 years. Here, we used it for evaluation of Down Syndrome subjects. The story recall subtests involves immediate free recall, cued recall, and delayed recall of short story material which is presented orally to subjects by the examiner. The RBMT-C is appealing for use in this population because the task is engaging, simple, and has been shown in other studies to be an effective measure of memory functions. Memory retention is the percentage of story elements recalled after a delay compared to right after the story is complete. Range: 0-100. A higher score means a better outcome.

Full Information

First Posted
April 8, 2015
Last Updated
November 19, 2019
Sponsor
HealthPartners Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02432716
Brief Title
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

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
October 18, 2018 (Actual)
Study Completion Date
October 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HealthPartners Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Down Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Insulin (glulisine), then Placebo
Arm Type
Experimental
Arm Description
Participants first receive one dose of Glulisine 20 IU/IN (.1ml/10 units intranasal in each nostril). After a washout period of 2 weeks, they then received one dose of placebo, Sterile Normal Saline 20 IU/IN (.1ml intransal in each nostril).
Arm Title
Placebo, then Insulin (glulisine)
Arm Type
Experimental
Arm Description
Participants first receive one dose of placebo, Sterile Normal Saline 20 IU/IN (.1ml intransal in each nostril). After a washout period of 2 weeks, they then received one dose of Glulisine 20 IU/IN (.1ml/10 units intranasal in each nostril).
Intervention Type
Drug
Intervention Name(s)
Insulin glulisine
Other Intervention Name(s)
insulin, glulisine, Apidra
Intervention Description
Insulin (glulisine) Glulisine 20 IU/IN (.1ml/10 units intranasal in each nostril), once per study
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator: Placebo Sterile Normal Saline 20 IU/IN (.1ml intransal in each nostril), once per study
Primary Outcome Measure Information:
Title
Safety Measured by Adverse Events
Description
Number of adverse and/or serious events
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Cognitive Change Measured by Fuld Object-Memory Evaluation (FOME)
Description
During the examination, a patient is presented with ten common objects they are asked to identify by touch. The test uses distraction to test recall. For all, a higher score indicates a better outcome. Learning curve is the number of objects the difference in the number of items they are able to correctly identify from the greater of trials 4 or 5 compared to trial 1. Range: 0-10 Total immediate recall is the number of objects recalled over all of the trials. Range: 0-50 Total delayed recall is the number of objects recalled after 5 minutes. Range: 0-10 Recognition memory is the number of items correct from a multiple choice list of three when unable to correctly identify items from delayed recall. Range: 0-10 Retention estimate is the number of items recalled after 5 minutes or being reminded with multiple choice. Range: 0-10
Time Frame
20 minutes
Title
Memory Retention Measured by Fuld Object-Memory Evaluation (FOME)
Description
Memory retention is the percentage of items correctly identify during the delayed recall trial compared storage trial 5. Range: 0-100 percent. A higher percentage indicates a better outcome.
Time Frame
20 minutes
Title
Cognitive Change Measured by Rivermead Behavioral Memory Test (RBMT-C)
Description
The RBMT-C provides an objective measure of everyday memory problems reported and observed in subjects with memory difficulties. The test is standardized for use with children ranging in age from 5 to 10 years. Here, we used it for evaluation of Down Syndrome subjects. The story recall subtests involves immediate free recall, cued recall, and delayed recall of short story material which is presented orally to subjects by the examiner. The RBMT-C is appealing for use in this population because the task is engaging, simple, and has been shown in other studies to be an effective measure of memory functions. For all, a higher score means a better outcome. Immediate Recall is the number of story elements recalled right after the story is complete. Range: 0-31 Delayed Recall is the number of story elements recalled after a delay. Range: 0-31
Time Frame
20 minutes
Title
Memory Retention Measured by Rivermead Behavioral Memory Test (RBMT-C).
Description
The RBMT-C provides an objective measure of everyday memory problems reported and observed in subjects with memory difficulties. The test is standardized for use with children ranging in age from 5 to 10 years. Here, we used it for evaluation of Down Syndrome subjects. The story recall subtests involves immediate free recall, cued recall, and delayed recall of short story material which is presented orally to subjects by the examiner. The RBMT-C is appealing for use in this population because the task is engaging, simple, and has been shown in other studies to be an effective measure of memory functions. Memory retention is the percentage of story elements recalled after a delay compared to right after the story is complete. Range: 0-100. A higher score means a better outcome.
Time Frame
20 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael H Rosenbloom, MD
Organizational Affiliation
HealthPartners Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
HealthPartners Neuroscience Center
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55130
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32077057
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.
Results Reference
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Investigation of the Safety of Intranasal Glulisine in Down Syndrome

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