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Trial record 42 of 89 for:    NIDDK endocrine and diabetes | Recruiting, Not yet recruiting, Available Studies

Memory Aid by Intranasal Insulin in Diabetes (MemAID) (MemAID)

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ClinicalTrials.gov Identifier: NCT02415556
Recruitment Status : Recruiting
First Posted : April 14, 2015
Last Update Posted : June 21, 2019
Sponsor:
Collaborators:
Novo Nordisk A/S
Medtronic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Vera Novak, Beth Israel Deaconess Medical Center

Brief Summary:
The main purpose of this study is to find the long-term effects of daily administration of 40 IU of intranasal insulin (INI) as compared to placebo (sterile saline) on cognition and memory in people with type 2 diabetes mellitus (DM), and non-diabetic controls over 24 weeks with a follow-up period for 24 weeks. Four groups will be tested: DM group treated with INI; DM group treated with placebo; control group treated with INI and the control group treated with placebo. The INI or placebo will be delivered into the nose. The investigators are interested to see whether INI can improve memory and cognition and blood flow in the brain in the type 2 DM group as compared to placebo and to the non-diabetic group over a long-term period.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Regular Human Insulin Drug: Placebo Phase 2 Phase 3

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Detailed Description:

The investigators propose a randomized controlled trial determining the long-term effects of intranasal insulin (INI) on cognition and memory in type 2 diabetes (DM) and non-DM groups. The investigators hypothesize that: 1) INI-treated adults with DM have better memory and functioning of specific cognitive domains and faster walking during a dual task than those treated with placebo and the control group; 2) Glycemic and insulin resistance and genetic markers for Alzheimer's disease (Apolipoprotein E4 [ApoE4]) may serve as predictors of positive responses to INI therapy; 3) INI treatment neither adversely affects systemic glycemic levels or the cardiovascular system nor causes weight gain.

Aim 1: To determine whether INI-treated type 2 DM adults have a) better memory and functioning of specific cognitive domains and b) faster dual-task gait speed and better daily living functioning than the placebo-treated and non-DM groups. Four groups will be tested: 60 DM subjects treated with insulin; 60 DM subjects treated with placebo; 45 control subjects treated with INI and 45 control subjects treated with placebo. These 210 patients are expected to complete treatment and 168 are expected to complete study by the study completion anticipated date.

The investigators will conduct a randomized, double-blind, placebo-controlled study in 120 older adults with type 2 DM and 90 non-DM controls examining whether 40 IU INI once daily over a 24-week period improves:

  • Specific domains of visuospatial attention and memory, verbal learning (primary outcomes);
  • Gait speed during a dual task (which is an excellent predictor of overall health), daily living functionality, and depression as compared to the DM group receiving sterile saline and the non-DM groups. The non-DM groups will provide reference of INI effects in a clinical phenotype of cognitive decline and insulin resistance that occurs with normal aging.

Aim 2: To identify a phenotype and long-term trajectory predicting clinically relevant response to INI therapy based on glycemic control, insulin resistance, endothelial and genetic markers.

  1. The investigators will determine a phenotype predicting a clinically relevant response to INI therapy and identify time-dependent trajectories of INI effects on cognition in the DM group vs. the placebo and the non-DM groups. Clinical predictors will be based on associations between cognitive function and/or gait and demographic, glycemic control, insulin resistance, endothelial and genetic (ApoE4) measures.
  2. The investigators will evaluate the dose-escalating trajectory of cognition, gait speed, and functionality during the 24 weeks of therapy and 24 weeks post-treatment and their dependence on the above-mentioned factors, and determine the time point when maximum effect was reached. INI therapy response is defined as a clinically relevant improvement on cognitive tests or in gait speed (as a continuous variable) or as responders vs. non-responders as compared to placebo within DM and non-DM groups (as a categorical variable).
  3. MRI substudy: The investigators will explore the long-term INI effects on regional perfusion, vasodilatation, and resting functional connectivity in 40 DM subjects pre- and post- INI/placebo administration at the beginning and at the end of intervention and their relationships to cognitive outcomes. Regional perfusion and vasodilatation will be measured by pseudo-continuous arterial spin labeling (PCASL) MRI at 3 Tesla, and resting-state functional connectivity will be quantified from low-frequency (0.01-0.08 Hz) fluctuations (LFF) of the whole-brain blood-oxygen-level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI).

Aim 3: To determine the long-term safety of INI vs. placebo with regard to glycemic control (fasting glucose, hemoglobin A1c [HbA1c], hypoglycemic episodes), vital signs, and body mass.

  1. The investigators will obtain measurements of fasting glucose, insulin, vital signs, and body mass at baseline, 2-months, 4-months, and 6-months follow-up and keep weekly logs monitoring glucose and adverse events.
  2. Safety substudy: In the first 20 DM patients treated with subcutaneous insulin, the investigators will conduct continuous glucose monitoring (CGM) OR 5 finger sticks/day (effective after 9/25/2017) for 1 week during baseline and during the first week of INI or placebo treatment to evaluate the INI effects on glycemic control, hypoglycemic episodes, and body weight.

This study may pave the way to potential treatment and/or cure of DM- and age-related cognitive decline.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 120 T2DM adults and 90 non-DM controls (as of 9/25/2017)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Memory Advancement by Intranasal Insulin in Type 2 Diabetes
Study Start Date : July 2015
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Experimental: Type 2 Diabetes Mellitus - Insulin
40 IU of regular human insulin once daily over 24 weeks
Drug: Regular Human Insulin
Regular human insulin 40 IU daily over 24 weeks
Other Name: Novolin R Novonordisk

Placebo Comparator: Type 2 Diabetes Mellitus - Placebo
Intranasal sterile saline once daily over 24 weeks
Drug: Placebo
Intranasal sterile saline 40 IU daily over 24 weeks
Other Name: Sterile normal saline

Experimental: Control - Insulin
40 IU of regular human insulin once daily over 24 weeks
Drug: Regular Human Insulin
Regular human insulin 40 IU daily over 24 weeks
Other Name: Novolin R Novonordisk

Placebo Comparator: Control - Placebo
Intranasal sterile saline once daily over 24 weeks
Drug: Placebo
Intranasal sterile saline 40 IU daily over 24 weeks
Other Name: Sterile normal saline




Primary Outcome Measures :
  1. Change from baseline Spatial Working Memory (SWM) between errors. [ Time Frame: Measured at weeks: 1 (twice, before and after intervention), 8, 16, 24 (last intervention), 32, 40, 48 (last follow-up) ]
    Spatial working memory - Difference between controls and diabetics at each time point

  2. Change from baseline Paired Associates Learning (PAL) total errors (adjusted). [ Time Frame: Measured at weeks: 1 (twice, before and after intervention), 8, 16, 24 (last intervention), 32, 40, 48 (last follow-up) ]
    Visuospatial learning and memory - Difference between controls and diabetics at each time point

  3. Change from baseline rapid visual processing (RVP) mean latency. [ Time Frame: Measured at weeks: 1 (twice, before and after intervention), 8, 16, 24 (last intervention), 32, 40, 48 (last follow-up) ]
    Rapid visual information processing - Difference between controls and diabetics at each time point

  4. Change from baseline gait speed normal walk and dual task (both in cm/s). [ Time Frame: Measured at weeks: 1 (twice, before and after intervention), 8, 16, 24 (last intervention), 32, 40, 48 (last follow-up) ]
    Mobility in terms of gait speed - Difference between controls and diabetics at each time point


Secondary Outcome Measures :
  1. Change in fasting plasma and capillary glucose (mg/dL) [ Time Frame: Measured weekly during 24 weeks of intervention (week 1-24). ]
    Long-term safety measure of intranasal insulin vs. placebo


Other Outcome Measures:
  1. Magnetic Resonance Imaging (MRI) (Vasoreactivity) - for 40 DM patients only [ Time Frame: At weeks: 1 (before intervention) and week 24 ( last intervention) ]
    Vasoreactivity will be measured by pseudo-continuous arterial spin labeling (PCASL) MRI at 3 Tesla



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women aged 50-85 years old
  • Able to walk for 6 minutes
  • Diabetes type 2 (DM) group: diagnosis and treatment for type 2 DM with non-insulin oral or injectable agents
  • Non-DM group with similar age range as the DM group, non-diabetic fasting plasma glucose (<126 mg/dL) and hemoglobin A1c (HbA1c) (<6.5%)
  • Participants capable of providing informed consent

Exclusion Criteria:

  • Type 2 DM treated with insulin (since 9/25/2017)
  • Type 1 DM
  • Intolerance to insulin
  • History of severe hypoglycemia
  • Participants who have >1 asymptomatic and/or symptomatic episode of hypoglycemia (glucose < 54 mg/dL) during finger stick or plasma glucose (cut off value since 6/11/2018)
  • Acute medical condition that required either hospitalization or surgery within the past 6 months (e.g., severe hypoglycemia, malignancies, myocardial infarction,stroke)
  • Liver or renal failure or transplant
  • Dementia (Mini Mental State Examination [MMSE] scores ≤20)
  • Current recreational drug or alcohol abuse
  • Serious systemic disease that would interfere with conduction of clinical trial (mild forms of neurological conditions e.g. Parkinson's Disease, autonomic neuropathy etc. would be allowed)
  • Magnetic Resonance Imaging (MRI) substudy in 40 DM patients only: claustrophobia and implants incompatible with 3-Tesla MRI
  • Safety substudy in 20 IDDM patients only: Insulin-treated type 2 diabetics with a C-peptide of <0.8 ng/mLd and fasting blood glucose >150 mg/dL will be excluded even without history of hypoglycemia during finger stick measurements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02415556


Contacts
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Contact: Laura Aponte-Becerra 617-632-8883 laponte@bidmc.harvard.edu
Contact: Jorge Trevino 617-632-8859 jtrevin1@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Laura Aponte-Becerra    617-632-8883    safelab@bidmc.harvard.edu   
Contact: Jorge Trevino    617-632-8859    safelab@bidmc.harvard.edu   
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Peter Novak, MD PhD    617-424-4101    PNOVAK2@PARTNERS.ORG   
Contact: Jorge Trevino    617-632-8884    jtrevin1@bidmc.harvard.edu   
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Novo Nordisk A/S
Medtronic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Vera Novak, PhD Beth Israel Deaconess Medical Center
Principal Investigator: Peter Novak, MD PhD Brigham and Women's Hospital
  Study Documents (Full-Text)

Documents provided by Vera Novak, Beth Israel Deaconess Medical Center:
Informed Consent Form  [PDF] March 25, 2019


Publications:
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Responsible Party: Vera Novak, Associate Professor of Neurology, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02415556     History of Changes
Other Study ID Numbers: 2015P000064
1R01DK103902-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 14, 2015    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: BWH's site data will be shared with BIDMC site upon BWH's site recruitment initiation
Keywords provided by Vera Novak, Beth Israel Deaconess Medical Center:
Type 2 Diabetes Mellitus
Intranasal Insulin
Placebo
Memory
Gait
Non diabetic older controls
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs