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| Name | Class |
|---|---|
| Boston University | OTHER |
| Joslin Diabetes Center | OTHER |
| Peking University | OTHER |
| University of Washington |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin vs. placebo | Experimental | Comparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes. |
|
| Healthy vs. Diabetic | Other | Comparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intranasal insulin | Drug | The acute effects of a single 40-IU dose of intranasal insulin |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
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Inclusion Criteria:
Diabetes group:
Control group:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vera Novak, MD PhD | Beth Israel Deaconess Medical Center, Harvard Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24101698 | Result | 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. | |
| 25249577 | Result | 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. |
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Thirty consented subjects, 15 type 2 diabetic and 14 controls completed the protocol. One control was excluded after starting the study. Screened participants that did not start study: 27 were excluded after screening visit, 7 withdrew consent. Enrollment Table list the characteristics of 29 participants who completed the protocol.
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| ID | Title | Description |
|---|---|---|
| FG000 | Diabetes Group: Placebo First | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo |
| FG001 | Diabetes Group: Insulin First | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo |
| FG002 | Control Group: Placebo First | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo |
| FG003 | Control Group: Insulin First | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Twenty nine consented subjects, 15 type 2 diabetic and 14 controls completed the protocol.
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo ( sterilesaline) in type 2 diabetes and the non-diabetic control group.Each participant received a single dose of insulin and a single dose of placebo on 2 consequent days in random order. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | T-score | Acute changes within 2 hours |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diabetes Group: Placebo | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the non-diabetic control group. The intranasal administration of insulin was safe, with no serious adverse events or hypoglycemic episodes and the protocol was feasible for participants. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Cardiac disorders | Cardiac disorders | Systematic Assessment | Healthy-Insulin : One control subject was identified to have un-diagnosed hypertension prior and after intranasal insulin administration. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Vera Novak | Beth Israel Deaconess Medical Center | 617-632-8680 | vnovak@bidmc.harvard.edu |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| OTHER |
| University of Arkansas | OTHER |
| VA Boston Healthcare System | FED |
| University of Massachusetts, Worcester | OTHER |
| Wake Forest University | OTHER |
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| Placebo | Drug | The acute effects of intranasal sterile saline. |
|
| BG001 | Diabetics | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo ( sterilesaline) in type 2 diabetes and the non-diabetic control group.Each participant received a single dose of insulin and a single dose of placebo on 2 consequent days in random order. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Diabetes Group: Insulin | Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the control group. |
| OG002 | Control Group: Placebo | Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the control group on cognitive function (Brief Visuospatial Memory test-Revised (BVMT-R)). |
| OG003 | Control Group: Insulin | Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the control group on cognitive function (Brief Visuospatial Memory test-Revised (BVMT-R)). |
|
|
| 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). | Posted | Mean | Standard Deviation | ml/100g/min/mmHg | Acute changes within 2 hours |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Diabetes Group: Insulin | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the non-diabetic control group. The intranasal administration of insulin was safe, with no serious adverse events or hypoglycemic episodes and the protocol was feasible for participants. | 0 | 15 | 0 | 15 |
| EG002 | Control Group: Placebo | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the non-diabetic control group. The intranasal administration of insulin was safe, with no serious adverse events or hypoglycemic episodes and the protocol was feasible for participants. | 0 | 15 | 0 | 15 |
| EG003 | Control Group: Insulin | Comparisons of acute effects of intranasal insulin or placebo on cerebral blood flow and cognition. Intranasal insulin: The acute effects of a single 40-IU dose of intranasal insulin vs. placebo in type 2 diabetes and the non-diabetic control group. The intranasal administration of insulin was safe, with no serious adverse events or hypoglycemic episodes and the protocol was feasible for participants. | 0 | 15 | 1 | 15 |
|
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| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |