Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart

Phase 1

Completed

• Conditions: Mild Cognitive Impairment; Alzheimer's Disease
• Interventions: Drug: Placebo; Drug: Insulin aspart

• Registration Number: NCT02462161
• Lead Sponsor: Wake Forest University Health Sciences

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.

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 Timeline

• Study Start: 2015-03-20
• Study First Submitted: 2015-06-01
• Study First Submitted QC: 2015-06-02
• Study First Posted: 2015-06-03
• Primary Completion: 2019-04-16
• Study Completion: 2019-04-16
• Status Verified: 2019-08
• Last Update Submitted: 2020-05-08
• Last Update Posted: 2020-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Insulin Aspart	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.

Primary Outcome Measures

Name	Time	Method
Change in cognition	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

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

Trial Locations

Locations (1)

Wake Forest Baptist Hospital; 🇺🇸 Winston-Salem, North Carolina, United States