Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02503501
Other study ID # IN-INSUL-MCI-AD
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date September 28, 2015
Est. completion date February 15, 2019

Study information

Verified date January 2020
Source HealthPartners Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study evaluates the safety and effectiveness of intranasal (IN) glulisine in patients with amnestic mild cognitive impairment (aMCI) and probable Alzheimer's disease. Half of participants will receive IN glulisine, while the other half will receive IN placebo.


Description:

Disruption of central nervous system (CNS) insulin signaling has been increasingly associated with Alzheimer's Disease pathogenesis, and consequently this disease has been referred to as a type III diabetes of the brain. Clinical trials of intranasal insulin in AD have demonstrated therapeutic effects of intranasal (IN) insulin in memory-impaired adults in terms of memory recall without significantly altering serum insulin or glucose levels. In this study, the investigators are investigating the chronic effects of the rapid acting insulin, glulisine, administered intranasally (IN) 20 IU two times daily in adults with amnestic-mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). The investigation will enroll n=90 subjects and follow them over a 6 month period.

This study has the following objectives:

1. Primary:

a. To measure the chronic effects of IN insulin glulisine on cognition and function in subjects with aMCI and probable mild AD over a 6 month period.

2. Secondary:

1. To measure the effect of IN insulin glulisine on mood in subjects with aMCI and mild AD over a 6 month period.

2. To measure the safety and efficacy of IN glulisine in aMCI and mild AD subjects with non-insulin dependent diabetes over a 6 month period.

3. Exploratory:

1. To measure the effect of IN delivery of insulin glulisine on parieto-temporal and posterior cingulate/precuneus glucose metabolism in subjects with aMCI and mild AD over a 6 month period.

2. To measure the chronic effect of IN delivery of insulin glulisine on AD-specific cerebrospinal (CSF) biomarkers (Abeta42, tau, and phospho-tau) in subjects with aMCI and mild AD over a 6 month period.


Recruitment information / eligibility

Status Terminated
Enrollment 49
Est. completion date February 15, 2019
Est. primary completion date February 11, 2019
Accepts healthy volunteers No
Gender All
Age group 50 Years to 90 Years
Eligibility Inclusion Criteria:

Subject is/has

- clinical and research diagnosis of amnestic-MCI OR probable mild AD in accordance with National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria

- Montreal Cognitive Assessment (MoCA) score 18-27

- Hachinski Ischemia Score <4

- 50-90 years of age

- Females at least 2 years post-menopausal or surgically sterile

- Proficiency in speaking, reading and understanding English

- Dedicated family member /caregiver, who will be able to attend all visits and report on subject's status

- (and family member/caregiver) provided fully informed written consent prior to participation. In the event that subject is legally unable to provide informed written consent due to deterioration in cognitive abilities, fully informed written consent must be provided by a legally authorized representative

- If AD, a brain computed tomography (CT) or magnetic resonance imaging (MRI) in the initial diagnostic workup or subsequent care that is compatible with the diagnosis of probable AD

Exclusion Criteria:

Subject has/have/is

- medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including, but not limited to brain tumor, active subdural hematoma, seizure disorder, multiple sclerosis, dementia with Lewy bodies, vascular dementia, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease, multiple system atrophy, frontotemporal dementia, normal pressure hydrocephalus, Huntington's disease, or Jakob-Creutzfeldt disease presenting as dementia

- medical history and/or clinically determined disorders: current B12 deficiency, chronic sinusitis, any untreated thyroid disease, significant head trauma and history of difficulty with smell and/or taste prior to AD diagnosis

- history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, condition known to affect absorption, distribution, metabolism, or excretion of drugs such as any hepatic, renal or gastrointestinal disease or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator

- previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies

- history of any psychiatric illness, with the exception of major depressive and anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, version 5, Text Revision (DSM-IV TR)) currently in remission or stable with treatment for > 2 yrs, or any other psychiatric condition that inclusion would pose a safety risk to the subject as determined by investigator

- currently taking any medications, herbals and food supplements that are medically/clinically contraindicated as determined by investigator in order to comply with procedural testing of cognitive function as well as ensure study safety. See list of prohibited medications and compounds

- undergone a recent change (<1mo) in their prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) or memantine.

- undergone a recent change (<1mo) in their selective serotonin re-uptake inhibitor (SSRI) or anti-depressant medication

- current or recent drug or alcohol abuse or dependence as defined by DSM-IV TR

- laboratory results that are medically relevant, in which inclusion would pose a safety risk to the subject as determined by investigator

- participated in any other research study at least 3 mos prior to this study

- an insulin allergy

Study Design


Intervention

Drug:
Insulin glulisine

Placebo
Bacteriostatic 0.9% Sodium Chloride

Locations

Country Name City State
United States HealthPartners Riverside Minneapolis Minnesota
United States HealthPartners Neuroscience Center Saint Paul Minnesota

Sponsors (1)

Lead Sponsor Collaborator
HealthPartners Institute

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13) The ADAS-Cog was developed as an outcome measure for global cognition in clinical trials for Alzheimer's disease. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. The modified ADAS-Cog 13-item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a total of 85 points (0: no cognitive impairment; 85: severe impairment). Baseline and 6 months
Primary Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). The total CDR ratings for each of the six cognitive/functional domains can be added to create a CDR sum of boxes (SOB). The overall SOB score ranges from 0 to 18; with 18 indicating severe impairment and 0 indicating no impairment. Baseline and 6 months
Primary Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ) The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The FAQ is a sum of scores ranging from 0 (normal) to 30 (complete dependence on others). Baseline and 6 months
See also
  Status Clinical Trial Phase
Completed NCT04513106 - Promoting Advance Care Planning for Persons With Early-stage Dementia in the Community: a Feasibility Trial N/A
Recruiting NCT06011681 - The Rapid Diagnosis of MCI and Depression in Patients Ages 60 and Over
Recruiting NCT04522739 - Spironolactone Safety in African Americans With Mild Cognitive Impairment and Early Alzheimer's Disease Phase 4
Active, not recruiting NCT03167840 - Falls Prevention Through Physical And Cognitive Training in Mild Cognitive Impairment N/A
Active, not recruiting NCT03676881 - Longitudinal Validation of a Computerized Cognitive Battery (Cognigram) in the Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease
Not yet recruiting NCT05041790 - A Clinical Trial to Evaluate the Efficacy and Safety of Choline Alfoscerate Compared to Placebo in Patients With Degenerative Mild Cognitive Impairment Phase 4
Recruiting NCT04121156 - High Definition Transcranial Direct Current Stimulation (HD-tDCS) in Patients With Mild Cognitive Impairment N/A
Recruiting NCT03605381 - MORbidity PRevalence Estimate In StrokE
Completed NCT02774083 - Cognitive Training Using Feuerstein Instrumental Enrichment N/A
Completed NCT01315639 - New Biomarker for Alzheimer's Disease Diagnostic N/A
Enrolling by invitation NCT06023446 - Can (Optical Coherence Tomography) Pictures of the Retina Detect Alzheimer's Disease at Its Earliest Stages?
Completed NCT04567745 - Automated Retinal Image Analysis System (EyeQuant) for Computation of Vascular Biomarkers Phase 1
Recruiting NCT05579236 - Cortical Disarray Measurement in Mild Cognitive Impairment and Alzheimer's Disease
Completed NCT03583879 - Using Gait Robotics to Improve Symptoms of Parkinson's Disease N/A
Not yet recruiting NCT03740178 - Multiple Dose Trial of MK-4334 in Participants With Alzheimer's Clinical Syndrome (MK-4334-005) Phase 1
Active, not recruiting NCT05204940 - Longitudinal Observational Biomarker Study
Recruiting NCT02663531 - Retinal Neuro-vascular Coupling in Patients With Neurodegenerative Disease N/A
Recruiting NCT06150352 - Sleep Apnea, Neurocognitive Decline and Brain Imaging in Patients With Subjective or Mild Cognitive Impairment
Recruiting NCT03507192 - Effects of Muscle Relaxation on Cognitive Function in Patients With Mild Cognitive Impairment and Early Stage Dementia. N/A
Completed NCT04817176 - MI-CBT Adherence Program for Lifestyle Interventions in Older Adults Early Phase 1