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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01206322
• Other study ID #: 1R21-DK088446301
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: April 2013

Study information

• Verified date: June 2019
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Intranasal insulin
The acute effects of a single 40-IU dose of intranasal insulin
• Placebo
The acute effects of intranasal sterile saline.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (9)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Boston University, Joslin Diabetes Center, Peking University, University of Arkansas, University of Massachusetts, Worcester, University of Washington, VA Boston Healthcare System, Wake Forest University

Country where clinical trial is conducted

United States, 

References & Publications (2)

Novak V, Milberg W, Hao Y, Munshi M, Novak P, Galica A, Manor B, Roberson P, Craft S, Abduljalil A. Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes. Diabetes Care. 2014;37(3):751-9. doi: 10.2337/dc13-1672. Epub 2013 Oc — View Citation

Zhang H, Hao Y, Manor B, Novak P, Milberg W, Zhang J, Fang J, Novak V. Intranasal insulin enhanced resting-state functional connectivity of hippocampal regions in type 2 diabetes. Diabetes. 2015 Mar;64(3):1025-34. doi: 10.2337/db14-1000. Epub 2014 Sep 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive Outcome: Brief Visuospatial Spatial Memory Test -Total Recall (Unit T Score)	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
Primary	Perfusion Outcome: Right Insular Cortex Perfusion (ml/100g/Min/mmHg)	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