Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart (SNIFF-Quick)

• ClinicalTrials.gov Identifier: NCT02462161
• Recruitment Status: Completed
• First Posted: June 3, 2015
• Last Update Posted: May 12, 2020
• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA); General Electric
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

Brief Summary:

This pilot clinical trial will examine the effects of intranasal insulin aspart on cognition, daily function, blood and cerebral spinal fluid markers of Alzheimer's disease, and amyloid deposition in the brain. Participants will be randomly assigned to receive insulin aspart or placebo during a 12-week treatment period.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease; Mild Cognitive Impairment	Drug: Insulin aspart; Drug: Placebo	Phase 1

Detailed Description:

A growing body of evidence suggests that insulin plays a role in normal memory processes and that insulin abnormalities may contribute to cognitive and brain changes associated with Alzheimer's disease (AD). Interestingly, insulin administered to the nasal cavity is transported within a few minutes into the brain, but does not affect blood sugar or insulin levels.

This trial will consist of a randomized double-blind, placebo-controlled parallel group trial in which 30 participants with AD or mild cognitive impairment (MCI) receive twice daily intranasal administrations of insulin aspart (20 IU) or placebo (saline), two times per day for 12 weeks. All participants will appoint a "support person" to answer a collateral questionnaire and supervise the administration of the study drug. All participants and study partners will undergo the intensive, structured training program in the self-management of intranasal insulin administration. Cognitive testing and blood collection will occur at baseline, after 6 weeks of treatment, and at the end of the 12 week treatment period. Participants will also receive a lumbar puncture to measure AD biomarkers in the subject's cerebral spinal fluid.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart
• Actual Study Start Date: March 20, 2015
• Actual Primary Completion Date: April 16, 2019
• Actual Study Completion Date: April 16, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Insulin Aspart; Fifteen randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive twice daily intranasal administrations of insulin aspart (20 IU) for 12 weeks.	Drug: Insulin aspart; Participants will administer 20 IU insulin aspart two times per day with an intranasal delivery device.; Other Name: NovoLog Fast-Acting Insulin Aspart
Placebo Comparator: Placebo; Fifteen randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive twice daily intranasal administrations of placebo (saline) for 12 weeks.	Drug: Placebo; Participants will administer placebo two times per day with an intranasal delivery device.; Other Name: Saline

Outcome Measures

Primary Outcome Measures :

1. Change in cognition [ Time Frame: 6 weeks and 12 weeks ]
   Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog)/mild cognitive impairment (MCI) scores and memory composite (summed Z scores from delayed story and list recall)

Secondary Outcome Measures :

1. Cerebral spinal fluid (CSF) and blood amyloid-beta, tau protein, and inflammatory markers [ Time Frame: Blood - every 6 weeks for 12 weeks; cerebral spinal fluid (CSF) - baseline and week 12 ]
2. MRI measure of cortical thickness in Alzheimer's disease (AD) -vulnerable regions [ Time Frame: Baseline and week 12 ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Previous or subsequent diagnosis of Alzheimer's disease or mild cognitive impairment
• Ability to communicate in English

Exclusion Criteria:

• Preexisting diabetes
• Clinically significant elevations in liver function test
• Clinically significant elevations in lipid profile
• Prior lumbar lumbar surgeries or other medical conditions that render lumbar punctures unsafe
• Hemoglobin <8 g/dl
• Significant neurologic disease that might affect cognition, other than Alzheimer's disease, including stroke, Parkinson's disease, multiple sclerosis, or recent severe head injury (within the last year) with loss of consciousness >30 minutes or with permanent neurologic sequelae
• Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease
• Current use of antipsychotic, anticonvulsant, anxiolytic, anticoagulant or sedative medications
• Current or previous use of glucose-lowering agents or insulin;
• Chronic use (≥ 3 times per week) of nasal sprays of any type for any indication
• Premenopausal status (defined as having had a period within the last year).

Contacts and Locations

Locations

United States, North Carolina

Wake Forest Baptist Hospital

Winston-Salem, North Carolina, United States, 27157

Sponsors and Collaborators

Wake Forest University Health Sciences

National Institute on Aging (NIA)

General Electric

Investigators

• Principal Investigator: Suzanne Craft, PhD; Wake Forest University Health Sciences

  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:

Informed Consent Form  [PDF] October 30, 2018

More Information

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02462161
• Other Study ID Numbers: IRB00026106; 5P50AG005136-30 ( U.S. NIH Grant/Contract )
• First Posted: June 3, 2015
• Last Update Posted: May 12, 2020
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Hypoglycemic Agents; Physiological Effects of Drugs