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

This study has been completed.
Sponsor:
Collaborators:
Boston University
Joslin Diabetes Center
Peking University
University of Washington
University of Arkansas
VA Boston Healthcare System
University of Massachusetts, Worcester
Wake Forest School of Medicine
Information provided by (Responsible Party):
Vera Novak, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01206322
First received: August 20, 2010
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Intranasal insulin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Enhancement of Cerebral Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • 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 and cognitive measures. [ Time Frame: acute changes within 48 hours ] [ Designated as safety issue: Yes ]
    The effects of insulin or placebo will be assessed acutely within 24 hours after each administration ( total 48 hours)


Secondary Outcome Measures:
  • Acute effects of a single 40-IU dose of intranasal insulin vs. placebo on regional vasoreactivity to CO2 challenge measured by 3-D continuous arterial spin labeling (CASL) MRI at 3 Tesla. [ Time Frame: Visit Day 2 and Day 3 ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: May 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin vs. placebo
Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition.
Drug: Intranasal insulin
The acute effects of a single 40-IU dose of intranasal insulin vs. placebo
Other Name: Novolin R

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.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01206322

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Boston University
Joslin Diabetes Center
Peking University
University of Washington
University of Arkansas
VA Boston Healthcare System
University of Massachusetts, Worcester
Wake Forest School of Medicine
Investigators
Principal Investigator: Vera Novak, MD PhD Beth Israel Deaconess Medical Center, Harvard Medical School
  More Information

No publications provided

Responsible Party: Vera Novak, MD PhD, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01206322     History of Changes
Other Study ID Numbers: 1R21-DK088446301
Study First Received: August 20, 2010
Last Updated: July 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Beth Israel Deaconess Medical Center:
diabetes, blood flow, brain perfusion, cognitive function

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014