Enhancement of Cerebral Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes

June 17, 2019 updated by: Vera Novak, Beth Israel Deaconess Medical Center

Our goal is to determine the acute effects of intranasal insulin on regional perfusion and cognition of older adults. We propose a pilot study to examine the effect of a single dose of intranasal insulin on regional vasoreactivity and cognitive functions in 30 subjects with T2DM and 30 healthy controls >50 years old using a double blinded, placebo-controlled, cross-over design.

Hypothesis 1: Intranasal insulin improves acutely regional perfusion and vasoreactivity in older patients with T2DM as compared with placebo and compared with the control group.

Hypothesis 2: Intranasal insulin improves cognitive functioning including attention, memory and executive function in diabetic patients as compared with placebo and compared with control group.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 2 diabetes mellitus (T2DM) is a major risk factor for vascular dementia. DM alters insulin transport across blood-brain barrier affecting perfusion and neuronal function. Intranasal administration enables effective delivery of insulin to the brain. Clinical studies demonstrated improvement of cognitive function and memory in healthy and cognitively impaired people.

Aim 1: To determine the acute effects of a single 40-IU dose of intranasal insulin vs. placebo on regional perfusion and vasoreactivity to CO2 challenge measured by 3-D continuous arterial spin labeling (CASL) MRI at 3 Tesla in the control and diabetic groups. We will use transcranial Doppler to determine the effects on intranasal insulin vs. placebo on cerebral autoregulation based on measurements of beat-to-beat pressure flow velocity relationship.

Aim 2: To determine whether intranasal insulin improves cognitive functioning in older T2DM patients as compared with placebo and the control group.

This translational study will address an important area about the effects of intranasal insulin on cerebral blood flow regulation and cognition in older diabetics that has not been studied. Intranasal insulin administration may provide a novel therapeutic target for prevention and treatment of microvascular disease and cerebrovascular complications of T2DM. If successful, this approach may have significant impact on the clinical management of large population of older adults with T2DM.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Diabetes group:

  • 30 men and women aged >50 years old diagnosed with T2DM and treated > 5 years with oral agents
  • Diabetes severity will be assessed from diabetes duration, hemoglobin A1C, and fasting glucose levels.

Control group:

  • 30 healthy men and women aged >50 years selected to have the same age and sex distributions as the diabetic subjects
  • Normotensive, not treated for any systemic disease, and have normal fasting blood glucose.

Exclusion Criteria:

  • Type 1 Diabetes Mellitus
  • History of severe hypoglycemia or hypoglycemic episode during home baseline monitoring
  • Positive stress test for CAD or other ischemic conditions
  • Carotid stenosis > 50% by medical history
  • History of a clinically documented stroke
  • Treatment with any medications administered intranasally including intranasal steroids
  • Any previous adverse or allergic reactions to insulin
  • Acute or unstable medical condition including Myocardial infarction or major illness and surgery within six months
  • Liver or renal failure or transplant
  • Uncontrolled hypertension (systolic BP >180 and/or diastolic BP >100 mm Hg or subjects taking more than 3 antihypertensive medications)
  • Seizure disorders
  • Malignant tumors
  • Clinical dementia (by history) or inability to follow details of the protocol(MMSE (Mini Mental Status Exam) score (≥3 points below the Comparative Normal Value for the subject's age group and education level, or ≤ 24)
  • Current recreational drug or alcohol abuse
  • Morbid obesity (BMI >40)
  • Inability to obtain permission for participation from the primary care physician
  • Transcranial Doppler (TCD) exclusion criterion - poor insonation window and TCD signal
  • MR exclusion criteria - any metal or bioimplants not compatible with 3 Tesla MRI and claustrophobia
  • Clinically significant and movement limiting hip, knee and/or back disorders or injury, and rheumatoid arthritis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Insulin vs. placebo
Comparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes.
Drug: Intranasal insulin
The acute effects of a single 40-IU dose of intranasal insulin
Other Names:
  • Novolin R
Drug: Placebo
The acute effects of intranasal sterile saline.
Other: Healthy vs. Diabetic
Comparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes.
Drug: Intranasal insulin
The acute effects of a single 40-IU dose of intranasal insulin
Other Names:
  • Novolin R
Drug: Placebo
The acute effects of intranasal sterile saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive Outcome: Brief Visuospatial Spatial Memory Test -Total Recall (Unit T Score)
Time Frame: Acute changes within 2 hours

To determine the acute effects of a single 40-IU dose of intranasal insulin vs. placebo on cognition and regional perfusion and vasoreactivity to CO2 challenge measured by 3-D continuous arterial spin labeling (CASL) MRI at 3 Tesla in the control and diabetic groups.

Cognitive outcome: Brief Visuospatial Spatial Memory test -Total Recall (unit T Score).

Perfusion outcome: Regional vasoreactivity (ml/100g/min/mmHg).

Each participant received a single dose of intranasal insulin (INI) or placebo on day 2 and a single dose dose of insulin or placebo on day 3 in a random order.

Acute effects on baseline perfusion, regional vasoreactivity and cognition were determined within 2 hours after administration of insulin or placebo.
Acute changes within 2 hours
Perfusion Outcome: Right Insular Cortex Perfusion (ml/100g/Min/mmHg)
Time Frame: Acute changes within 2 hours

To determine the acute effects of a single 40-IU dose of intranasal insulin vs. placebo on cognition and regional perfusion and vasoreactivity to CO2 challenge measured by 3-D continuous arterial spin labeling (CASL) MRI at 3 Tesla in the control and diabetic groups.

Cognitive outcome: Brief Visuospatial Spatial Memory test -Total Recall (unit T Score).

Perfusion outcome: Regional vasoreactivity (ml/100g/min/mmHg).
Acute changes within 2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

Boston University
Peking University
University of Washington
University of Massachusetts, Worcester
University of Arkansas
Joslin Diabetes Center
Wake Forest University
VA Boston Healthcare System

Investigators

  • Principal Investigator: Vera Novak, MD PhD, Beth Israel Deaconess Medical Center, Harvard Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

August 20, 2010

First Submitted That Met QC Criteria

September 20, 2010

First Posted (Estimate)

September 21, 2010

Study Record Updates

Last Update Posted (Actual)

June 26, 2019

Last Update Submitted That Met QC Criteria

June 17, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R21-DK088446301

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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