Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 120 Days (SL120) - Full Text View

Purpose

The study will examine the effects of intranasally administered long-acting insulin detemir on cognition in persons with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI). The rationale for these studies is derived from growing evidence that insulin contributes to multiple brain functions, and that insulin dysregulation can contribute to AD pathogenesis. Thus, therapies aimed at restoring normal insulin signaling in the CNS may have beneficial effects on brain function. Intranasal administration of insulin increases insulin signaling in the brain without raising peripheral levels and causing hypoglycemia. Insulin detemir is an insulin analogue that may have better action in brain than other insulin formulations because of its albumin binding properties. The investigators will test the therapeutic effects of intranasally-administered insulin detemir in a study in which participants will receive insulin detemir, regular insulin, or placebo over a four month period. The investigators will test the hypothesis that insulin and insulin detemir will both improve memory and daily functioning in persons with AD/aMCI compared with placebo, but that insulin detemir will have the greatest effect.

Condition	Intervention	Phase
Alzheimer's Disease Mild Cognitive Impairment	Drug: Saline Drug: Insulin detemir Drug: Insulin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 120 Days (SL120)

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

Drug Information available for: Insulin Insulin human Insulin detemir

Genetic and Rare Diseases Information Center resources: Familial Alzheimer Disease

U.S. FDA Resources

Further study details as provided by Suzanne Craft, Wake Forest School of Medicine:

Primary Outcome Measures:

Verbal Memory Composite [ Time Frame: Change from Baseline in Verbal Memory at 16 weeks ]
The composite will consist of the sum of Z scores for Delayed Story Recall and Delayed List Recall

Secondary Outcome Measures:

Glucose Tolerance [ Time Frame: Change from Baseline in Glucose Tolerance at 16 Weeks ]
Subjects will undergo oral glucose tolerance test (OGTT) to assess glucose tolerance
Cerebral Blood Flow [ Time Frame: Change from Baseline in Cerebral Blood Flow at 16 Weeks ]
Functional MRI and arterial-spin labeling perfusion MRI
Cerebral Spinal Fluid (CSF) Biomarkers of AD [ Time Frame: Change from Baseline in CSF Biomarkers at 16 Weeks ]
CSF Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.
Plasma Biomarkers of AD [ Time Frame: Change from Baseline in Plasma Biomarkers at 16 Weeks ]
Plasma Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.
Executive Function Composite [ Time Frame: Change from Baseline in Executive Functioning at 16 Weeks ]
Sum of Z Scores from Dot Counting Test (test of executive functioning) and Benton Visual Retention Test Form F&G (a test of visual working memory)
Functional Ability [ Time Frame: Change from Baseline in Functional Ability at 16 Weeks ]
Subjects will have a collateral informant (i.e., spouse or friend) rate the subjects' ability to carry out activities of daily living on the Dementia Severity Rating Scale.
The Alzheimer's Disease Assessment Scale-Cognitive [ADAS-Cog/Alzheimer's Disease Cooperative Study (ADCS)] - MCI revision [ Time Frame: Change from Baseline in this measure at 16 Weeks ]
This cognitive screening measure contains measures of confrontational naming, following commands, constructional praxis, ideational praxis, orientation, and language production and comprehension.


Estimated Enrollment:	36
Study Start Date:	November 2011
Estimated Study Completion Date:	March 2017
Estimated Primary Completion Date:	March 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Saline	Drug: Saline Saline, administered intranasally twice per day for a 16 week duration Other Name: Saline solution
Experimental: Insulin Detemir 20IU of Insulin Detemir taken twice per day (40IU total per day)	Drug: Insulin detemir 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day) Other Name: Levemir
Experimental: Insulin 20IU Insulin, administered twice per day (40IU total per day)	Drug: Insulin 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day) Other Name: Novolin R

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Eligibility


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

Criteria

Inclusion Criteria:

Age 50-89
Diagnosed with mild cognitive impairment, or mild/moderate AD

Exclusion Criteria:

Excessively high or low blood pressure, heart rate
Pre-existing diabetes not controlled by exercise/diet
Previous/current use of insulin
Significant elevations in lipids, liver enzymes
Menstrual period within the last 12 months
Significant neurological or medical disorder (other than AD)
Significant use of nasal decongestants
Current use of anti-psychotic, anti-convulsive, anxiolytic, glucocorticoids, or sedative medications

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01595646

Locations


United States, North Carolina
Wake Forest Baptist Hospital
Winston-Salem, North Carolina, United States, 27157
United States, Washington
VA Puget Sound Health Care System - American Lake Division
Tacoma, Washington, United States, 98493

Sponsors and Collaborators

Wake Forest University Health Sciences

Alzheimer's Association

Investigators


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

More Information


Responsible Party:	Suzanne Craft, Research Director, Sticht Center on Aging, Wake Forest School of Medicine
ClinicalTrials.gov Identifier:	NCT01595646 History of Changes
Other Study ID Numbers:	IRB00023230 ZEN-10-173646US ( Other Grant/Funding Number: Alzheimer's Association )
Study First Received:	May 8, 2012
Last Updated:	November 30, 2016

Keywords provided by Suzanne Craft, Wake Forest School of Medicine:


Memory Intranasal insulin Alzheimer's disease Mild Cognitive Impairment

Additional relevant MeSH terms:


Alzheimer Disease Cognition Disorders Mild Cognitive Impairment Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases	Neurocognitive Disorders Mental Disorders Insulin, Globin Zinc Insulin Insulin Detemir Insulin, Long-Acting Hypoglycemic Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017

Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 120 Days (SL120) (SL120)