Memory Aid by Intranasal Insulin in Diabetes (MemAID)
Information source: Beth Israel Deaconess Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes Mellitus
Intervention: Regular Human Insulin (Drug); Placebo (Drug)
Phase: Phase 2/Phase 3
Status: Not yet recruiting
Sponsored by: Beth Israel Deaconess Medical Center Official(s) and/or principal investigator(s): Vera Novak, PhD, Principal Investigator, Affiliation: Beth Israel Deaconess Medical Center
Overall contact: Daniela A Pimentel, Phone: 617-632-8883, Email: dpiment1@bidmc.harvard.edu
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.
Clinical Details
Official title: Memory Advancement by Intranasal Insulin in Type 2 Diabetes
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change in Paired Associates Learning (PAL) total errors (adjusted)Change in Gait Speed Change in Fasting glucose
Secondary outcome: Magnetic Resonance Imaging (MRI) (Vasoreactivity)Hypoglycemic episodes
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: 100 DM subjects treated with insulin; 100 DM subjects treated with placebo; 100
control subjects treated with INI and 100 control subjects treated with placebo.
The investigators will conduct a randomized, double-blind, placebo-controlled study in 200
older adults with type 2 DM and 200 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 and 40 non-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) 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.
Eligibility
Minimum age: 50 Years.
Maximum age: 85 Years.
Gender(s): Both.
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 or insulin
- 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%)
Exclusion Criteria:
- Type 1 DM
- Intolerance to insulin
- History of severe hypoglycemia
- Participants who have >1 asymptomatic and/or symptomatic episode of hypoglycemia
(glucose < 70 mg/dL) during continuous glucose monitoring (CGM) or home measurements
- Acute medical condition that required either hospitalization or surgery within the
past 6 months (e. g., severe hypoglycemia, malignancies, myocardial infarction,stroke)
- Severe chronic sinus problems or allergies
- Liver or renal failure or transplant
- Dementia (Mini Mental State Examination [MMSE] scores ≤20)
- Current recreational drug or alcohol abuse
- Morbid obesity (body mass index [BMI] >45)
- Serious systemic disease that would interfere with conduction of clinical trial
- Magnetic Resonance Imaging (MRI) substudy: claustrophobia and implants incompatible
with 3-Tesla MRI
Locations and Contacts
Daniela A Pimentel, Phone: 617-632-8883, Email: dpiment1@bidmc.harvard.edu Additional Information
Starting date: July 2015
Last updated: April 13, 2015
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