Type 2 Diabetes MellitusPhase 2NCT01206322
Enhancement of Cerebral Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes
A Phase 2 study testing Intranasal insulin in people with Type 2 Diabetes Mellitus, run by Beth Israel Deaconess Medical Center at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 50 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Intranasal insulin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Apr 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
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.
Read the 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.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Intranasal insulin, Placebo
- Keywords
- diabetes, blood flow, brain perfusion, cognitive function
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal insulinDrug
Also called Novolin R
The acute effects of a single 40-IU dose of intranasal insulin
PlaceboDrug
The acute effects of intranasal sterile saline.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Intranasal insulin; Drug: Placebo |
| 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. Receives: Drug: Intranasal insulin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Acute changes within 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2010 (estimated)
- Study startMay 2010
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University, Joslin Diabetes Center, Peking University, University of Washington, University of Arkansas, VA Boston Healthcare System, University of Massachusetts, Worcester, Wake Forest University
- Responsible party
- Principal investigator, Vera Novak, Beth Israel Deaconess Medical Center
- Investigators
- Vera Novak, MD PhD, Principal investigator, Beth Israel Deaconess Medical Center, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01206322
- Sponsor's protocol ID
- 1R21-DK088446301
- Status last verified
- Jun 2019
- First submitted
- 20 Aug 2010
- Last updated
- 26 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24101698Zhang 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.
PubMed 25249577
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancement of Cerebral Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT01206322
- Acronym / sponsor ID
- 1R21-DK088446301
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- diabetes, blood flow, brain perfusion, cognitive function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- Boston University, Joslin Diabetes Center, Peking University, University of Washington, University of Arkansas, VA Boston Healthcare System, University of Massachusetts, Worcester, Wake Forest University
- Study start
- May 2010
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 21 Sep 2010 (estimated)
- Results
- Posted 28 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin vs. placebo | Experimental | Drug: Intranasal insulin, Drug: PlaceboComparisons 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 | Drug: Intranasal insulin, Drug: PlaceboComparisons of acute effects of intranasal insulin or placebo (saline) on cerebral blood flow and cognition in healthy controls and type 2 diabetes. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intranasal insulinAlso: Novolin RThe acute effects of a single 40-IU dose of intranasal insulin | Drug | Healthy vs. Diabetic, Insulin vs. placebo |
| PlaceboThe acute effects of intranasal sterile saline. | Drug | Healthy vs. Diabetic, Insulin vs. placebo |
Primary outcome
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.
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24101698Novak 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.
- Results publication: PubMed 25249577Zhang 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.
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vera Novak, MD PhD principal investigator
Beth Israel Deaconess Medical Center, Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intranasal insulin in people with Type 2 Diabetes Mellitus, run by Beth Israel Deaconess Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Outcome: Brief Visuospatial Spatial Memory Test -Total Recall (Unit T Score) (time frame: Acute changes within 2 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01206322, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2019.