Expired Study
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Boston, Massachusetts 02215


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.


Study summary:

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.


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


Study is Available At:


Original ID:

1R21-DK088446301


NCT ID:

NCT01206322


Secondary ID:


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

50 Years


Maximum Age:

85 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Beth Israel Deaconess Medical Center


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

30


Enrollment Type:

Actual


Overall Contact Information

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

Study Dates

Start Date:May 2010
Completion Date:April 2013
Completion Type:Actual
Primary Completion Date:April 2013
Primary Completion Type:Actual
Verification Date:June 2019
Last Changed Date:June 17, 2019
First Received Date:August 20, 2010
First Results Date:July 24, 2014

Study Outcomes

Outcome Type:Primary Outcome
Measure:Perfusion Outcome: Right Insular Cortex Perfusion (ml/100g/Min/mmHg)
Time Frame:Acute changes within 2 hours
Safety Issues:False
Description: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 diab
Outcome Type:Primary Outcome
Measure:Cognitive Outcome: Brief Visuospatial Spatial Memory Test -Total Recall (Unit T Score)
Time Frame:Acute changes within 2 hours
Safety Issues:False
Description: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 diab

Study Interventions

Intervention Type:Drug
Name:Intranasal insulin
Description:The acute effects of a single 40-IU dose of intranasal insulin
Arm Name:Insulin vs. placebo
Other Name:Novolin R
Intervention Type:Drug
Name:Placebo
Description:The acute effects of intranasal sterile saline.
Arm Name:Insulin vs. placebo

Study Arms

Study Arm Type:Experimental
Arm Name:Insulin vs. placebo
Description:Comparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes.
Study Arm Type:Other
Arm Name:Healthy vs. Diabetic
Description:Comparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Beth Israel Deaconess Medical Center
Agency Class:Other
Agency Type:Collaborator
Agency Name:Boston University

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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 Oct 7.
PMID:24101698
Reference Type:Results Reference
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.
PMID:25249577

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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