Type 2 Diabetes MellitusPhase 2MemAIDNCT02415556

Memory Aid by Intranasal Insulin in Diabetes (MemAID)

A Phase 2 study testing Regular Human Insulin in people with Type 2 Diabetes Mellitus, run by Beth Israel Deaconess Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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?: Regular Human Insulin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 289 participants
Where: 2 sitesUnited States
Study dates: 6 Oct 2015to 31 May 2020
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

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

Who cannot join

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)

Show all 12Show fewer

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Brigham and Women's Hospital
Boston, Massachusetts, 02215
Vera Novak
Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Memory Advancement by Intranasal Insulin in Type 2 Diabetes

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.

Read the 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.

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.
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).
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.

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.
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.

Conditions: Type 2 Diabetes Mellitus
Being tested: Regular Human Insulin, Placebo
Keywords: Type 2 Diabetes Mellitus, Intranasal Insulin, Placebo, Memory, Gait, Non diabetic older controls
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Regular Human InsulinDrug
Also called Novolin R Novonordisk
Regular human insulin 40 IU daily over 24 weeks
PlaceboDrug
Also called Sterile normal saline
Intranasal sterile saline 40 IU daily over 24 weeks

Study groups in NCT02415556
Study group	Role	What they receive
Type 2 Diabetes Mellitus - Insulin	Experimental	40 IU of regular human insulin once daily over 24 weeks Receives: Drug: Regular Human Insulin
Type 2 Diabetes Mellitus - Placebo	Placebo comparator	Intranasal sterile saline once daily over 24 weeks Receives: Drug: Placebo
Control - Insulin	Experimental	40 IU of regular human insulin once daily over 24 weeks Receives: Drug: Regular Human Insulin
Control - Placebo	Placebo comparator	Intranasal sterile saline once daily over 24 weeks Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Gait Speed Normal Walk (cm/s).
Gait speed normal walk (cm/s) - difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Measured: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Gait Speed Dual-task (cm/s).
Gait speed dual-task (cm/s) - walking and counting backwards (subtracting 7) difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Measured: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Executive Function Composite z Score
The executive function composite score was calculated as a sum of Paired Associates Learning (PAL) and Spatial Working Memory (SWM) z-scores (range -2 to +2, 0 indicates the mean; higher score indicates worse outcome). Paired Associates Learning - raw score of Total Errors Adjusted (range 0-120) was converted to z-score. Spatial Working Memory - raw score SWM-Between Errors (range 0-42) and raw score of SWM-Strategy (range 8-56) were converted to z-scores. Executive function composite scores were compared between:
Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Measured: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Verbal Memory Composite z Score
Verbal memory composite score was calculated as the sum of Verbal Recognition Memory (VRM) z scores ( 0 indicates the mean; lower score indicates worse outcome). VRM- Free Recall raw score (range 0-12), immediate and delayed VRM-Recognition raw score (range 0-24) were converted to z-scores. Verbal memory composite scores were compared between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Measured: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).

Secondary outcomes (2)

Fasting Plasma Glucose (mg/dL).
Long-term safety measure of fasting plasma glucose difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Measured: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Weight (kg).
Long-term safety measure of weight difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Measured: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Oct 201531 May 2020

First posted14 Apr 2015 (estimated)
Study start6 Oct 2015
Primary completion31 May 2020
Study completion31 May 2020

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 (8)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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: 289 signed ICF. 244 were randomized (115 T2DM adults and 129 non-DM controls). 79 T2DM adults and 90 non-DM controls completed intervention (as of 4/23/2020)
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 289 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02415556
Sponsor's protocol ID: 2015P000064
Other IDs: 1R01DK103902-01A1
Acronym: MemAID
Status last verified: May 2022
First submitted: 23 Mar 2015
Last updated: 19 May 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Lioutas VA, Alfaro-Martinez F, Bedoya F, Chung CC, Pimentel DA, Novak V. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke. Transl Stroke Res. 2015 Aug;6(4):264-75. doi: 10.1007/s12975-015-0409-7. Epub 2015 Jun 5.
PubMed 26040423
Lioutas VA, Novak V. Intranasal insulin neuroprotection in ischemic stroke. Neural Regen Res. 2016 Mar;11(3):400-1. doi: 10.4103/1673-5374.179040. No abstract available.
PubMed 27127468
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.
PubMed 25249577
Galindo-Mendez B, Trevino JA, McGlinchey R, Fortier C, Lioutas V, Novak P, Mantzoros CS, Ngo L, Novak V. Memory advancement by intranasal insulin in type 2 diabetes (MemAID) randomized controlled clinical trial: Design, methods and rationale. Contemp Clin Trials. 2020 Feb;89:105934. doi: 10.1016/j.cct.2020.105934. Epub 2020 Jan 7.
PubMed 31923471
Trevino JT, Quispe RC, Khan F, Novak V. Non-Invasive Strategies for Nose-to-Brain Drug Delivery. J Clin Trials. 2020;10(7):439. Epub 2020 Dec 10.
PubMed 33505777
Novak V, Mantzoros CS, Novak P, McGlinchey R, Dai W, Lioutas V, Buss S, Fortier CB, Khan F, Aponte Becerra L, Ngo LH. MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial. J Neurol. 2022 Sep;269(9):4817-4835. doi: 10.1007/s00415-022-11119-6. Epub 2022 Apr 28.
PubMed 35482079
Isaza-Pierrotti DF, Khan F, Novak P, Lioutas V, Mantzoros CS, Ngo LH, Novak V. Dropout risk and effectiveness of retention strategies in the Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Clinical Trial. Contemp Clin Trials. 2023 Feb;125:107057. doi: 10.1016/j.cct.2022.107057. Epub 2022 Dec 17.
PubMed 36539060
Trevino JA, Novak P. TS-HDS and FGFR3 antibodies in small fiber neuropathy and Dysautonomia. Muscle Nerve. 2021 Jul;64(1):70-76. doi: 10.1002/mus.27245. Epub 2021 Apr 15.
PubMed 33792960

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 19 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Memory Advancement by Intranasal Insulin in Type 2 Diabetes
ClinicalTrials.gov ID: NCT02415556
Acronym / sponsor ID: MemAID / 2015P000064
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus, Intranasal Insulin, Placebo, Memory, Gait, Non diabetic older controls
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 289 participants (actual)
Lead sponsor: Beth Israel Deaconess Medical CenterUniversity, hospital or other
Collaborators: Novo Nordisk A/S, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: 6 Oct 2015 (actual)
Primary completion: 31 May 2020 (actual)
Study completion: 31 May 2020 (actual)
First posted: 14 Apr 2015 (estimated)
Results: Posted 17 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

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.
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).
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.

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.
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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: 289 signed ICF. 244 were randomized (115 T2DM adults and 129 non-DM controls). 79 T2DM adults and 90 non-DM controls completed intervention (as of 4/23/2020)

Arm	Type	Receives
Type 2 Diabetes Mellitus - Insulin	Experimental	Drug: Regular Human Insulin40 IU of regular human insulin once daily over 24 weeks
Type 2 Diabetes Mellitus - Placebo	Placebo comparator	Drug: PlaceboIntranasal sterile saline once daily over 24 weeks
Control - Insulin	Experimental	Drug: Regular Human Insulin40 IU of regular human insulin once daily over 24 weeks
Control - Placebo	Placebo comparator	Drug: PlaceboIntranasal sterile saline once daily over 24 weeks

Who may qualify

Ages: 50 to 85 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (12 listed)

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)

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
Regular Human InsulinAlso: Novolin R NovonordiskRegular human insulin 40 IU daily over 24 weeks	Drug	Control - Insulin, Type 2 Diabetes Mellitus - Insulin
PlaceboAlso: Sterile normal salineIntranasal sterile saline 40 IU daily over 24 weeks	Drug	Control - Placebo, Type 2 Diabetes Mellitus - Placebo

Primary outcome

Gait Speed Normal Walk (cm/s).
Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Gait speed normal walk (cm/s) - difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Gait Speed Dual-task (cm/s).
Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Gait speed dual-task (cm/s) - walking and counting backwards (subtracting 7) difference between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Executive Function Composite z Score
Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
The executive function composite score was calculated as a sum of Paired Associates Learning (PAL) and Spatial Working Memory (SWM) z-scores (range -2 to +2, 0 indicates the mean; higher score indicates worse outcome). Paired Associates Learning - raw score of Total Errors Adjusted (range 0-120) was converted to z-score. Spatial Working Memory - raw score SWM-Between Errors (range 0-42) and raw score of SWM-Strategy (range 8-56) were converted to z-scores. Executive function composite scores were compared between: Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.
Verbal Memory Composite z Score
Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Verbal memory composite score was calculated as the sum of Verbal Recognition Memory (VRM) z scores ( 0 indicates the mean; lower score indicates worse outcome). VRM- Free Recall raw score (range 0-12), immediate and delayed VRM-Recognition raw score (range 0-24) were converted to z-scores. Verbal memory composite scores were compared between Type 2 Diabetes Mellitus - Insulin vs. Type 2 Diabetes Mellitus - Placebo, Control - Insulin vs. Control - Placebo.

2 secondary outcomes

Fasting Plasma Glucose (mg/dL).
Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).
Weight (kg).
Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).

Results and safety

Results posted to the registry on 17 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Type 2 Diabetes Mellitus - Insulin	57	32
Type 2 Diabetes Mellitus - Placebo	58	37
Control - Insulin	65	43
Control - Placebo	64	44

Primary outcome: Gait Speed Normal Walk (cm/s).

Time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).. Mean (Standard Deviation). Unit: cm/s

Measure	Type 2 Diabetes Mellitus - Insulin n = 51	Type 2 Diabetes Mellitus - Placebo n = 55	Control - Insulin n = 58	Control - Placebo n = 59
Baseline	112.23 (22.94)	103.42 (21.04)	121.58 (21.87)	119.51 (15.61)
On-treatment average	112.43 (22.03)	105.83 (21.27)	123.89 (23.36)	119.44 (18.60)
Post-treatment average	113.12 (19.60)	107.27 (23.16)	124.79 (24.75)	120.50 (19.33)

Type 2 Diabetes Mellitus - Insulin vs Type 2 Diabetes Mellitus - Placebo: Mean Difference (Final Values): 6.52 (95% CI 0.81 to 12.23), p = 0.025, Mixed Models Analysis
Control - Insulin vs Control - Placebo: Mean Difference (Final Values): 5.28 (95% CI -0.03 to 10.60), p = 0.051, Mixed Models Analysis

Population analysed: Intention-to-treat analyses (Model 1) included data from 223 randomized subjects who completed the baseline visit.

Primary outcome: Gait Speed Dual-task (cm/s).

Measure	Type 2 Diabetes Mellitus - Insulin n = 51	Type 2 Diabetes Mellitus - Placebo n = 55	Control - Insulin n = 58	Control - Placebo n = 59
Baseline	104.23 (23.30)	93.18 (22.71)	109.44 (24.40)	110.24 (16.50)
On-treatment average	105.34 (23.59)	98.27 (22.39)	114.66 (25.11)	112.58 (17.99)
Post-treatment average	108.77 (20.49)	102.22 (21.02)	117.29 (26.73)	113.08 (20.60)

Type 2 Diabetes Mellitus - Insulin vs Type 2 Diabetes Mellitus - Placebo: Mean Difference (Final Values): 8.31 (95% CI 2.33 to 14.29), p = 0.007, Mixed Models Analysis
Control - Insulin vs Control - Placebo: Mean Difference (Final Values): 2.71 (95% CI -2.90 to 8.32), p = 0.342, Mixed Models Analysis

Population analysed: Intention-to-treat analyses (Model 1) included data from 223 randomized subjects who completed the baseline visit.

Primary outcome: Executive Function Composite z Score

Measure	Type 2 Diabetes Mellitus - Insulin n = 51	Type 2 Diabetes Mellitus - Placebo n = 55	Control - Insulin n = 58	Control - Placebo n = 59
Baseline	0.84 (2.08)	1.40 (2.30)	0.46 (2.25)	0.66 (2.22)
On-treatment average	0.13 (2.11)	0.47 (2.48)	-0.51 (2.56)	0.14 (2.34)
Post-treatment average	-0.19 (2.16)	-0.11 (2.44)	-1.08 (2.38)	-0.31 (2.43)

Type 2 Diabetes Mellitus - Insulin vs Type 2 Diabetes Mellitus - Placebo: Mean Difference (Final Values): -0.37 (95% CI -0.87 to 0.13), p = 0.144, Mixed Models Analysis
Control - Insulin vs Control - Placebo: Mean Difference (Final Values): -0.64 (95% CI -1.11 to -0.16), p = 0.008, Mixed Models Analysis

Population analysed: Intention-to-treat analyses (Model 1) included data from 223 randomized subjects who completed the baseline visit.

Primary outcome: Verbal Memory Composite z Score

Measure	Type 2 Diabetes Mellitus - Insulin n = 51	Type 2 Diabetes Mellitus - Placebo n = 55	Control - Insulin n = 58	Control - Placebo n = 59
Baseline	-0.74 (2.72)	-0.89 (3.02)	0.07 (2.69)	-0.22 (2.33)
On-treatment average	-0.16 (2.31)	-0.50 (2.20)	0.34 (2.16)	-0.01 (2.34)
Post-treatment average	0.05 (2.21)	-0.24 (1.98)	1.01 (1.82)	0.23 (2.56)

Type 2 Diabetes Mellitus - Insulin vs Type 2 Diabetes Mellitus - Placebo: Mean Difference (Final Values): 0.35 (95% CI -0.13 to 0.83), p = 0.149, Mixed Models Analysis
Control - Insulin vs Control - Placebo: Mean Difference (Final Values): 0.35 (95% CI -0.11 to 0.80), p = 0.134, Mixed Models Analysis

Population analysed: Intention-to-treat analyses (Model 1) included data from 223 randomized subjects who completed the baseline visit.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 48 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Type 2 Diabetes Mellitus - Insulin	0 of 51 (0%)	31 of 51 (60.8%)	0 of 51
Type 2 Diabetes Mellitus - Placebo	1 of 55 (1.8%)	37 of 55 (67.3%)	0 of 55
Control - Insulin	2 of 58 (3.4%)	33 of 58 (56.9%)	0 of 58
Control - Placebo	3 of 59 (5.1%)	33 of 59 (55.9%)	0 of 59

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26040423Lioutas VA, Alfaro-Martinez F, Bedoya F, Chung CC, Pimentel DA, Novak V. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke. Transl Stroke Res. 2015 Aug;6(4):264-75. doi: 10.1007/s12975-015-0409-7. Epub 2015 Jun 5.
Background: PubMed 27127468Lioutas VA, Novak V. Intranasal insulin neuroprotection in ischemic stroke. Neural Regen Res. 2016 Mar;11(3):400-1. doi: 10.4103/1673-5374.179040. No abstract available.
Background: 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.
Background: PubMed 31923471Galindo-Mendez B, Trevino JA, McGlinchey R, Fortier C, Lioutas V, Novak P, Mantzoros CS, Ngo L, Novak V. Memory advancement by intranasal insulin in type 2 diabetes (MemAID) randomized controlled clinical trial: Design, methods and rationale. Contemp Clin Trials. 2020 Feb;89:105934. doi: 10.1016/j.cct.2020.105934. Epub 2020 Jan 7.
Background: PubMed 33505777Trevino JT, Quispe RC, Khan F, Novak V. Non-Invasive Strategies for Nose-to-Brain Drug Delivery. J Clin Trials. 2020;10(7):439. Epub 2020 Dec 10.
Results publication: PubMed 35482079Novak V, Mantzoros CS, Novak P, McGlinchey R, Dai W, Lioutas V, Buss S, Fortier CB, Khan F, Aponte Becerra L, Ngo LH. MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial. J Neurol. 2022 Sep;269(9):4817-4835. doi: 10.1007/s00415-022-11119-6. Epub 2022 Apr 28.
Derived from this study: PubMed 36539060Isaza-Pierrotti DF, Khan F, Novak P, Lioutas V, Mantzoros CS, Ngo LH, Novak V. Dropout risk and effectiveness of retention strategies in the Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Clinical Trial. Contemp Clin Trials. 2023 Feb;125:107057. doi: 10.1016/j.cct.2022.107057. Epub 2022 Dec 17.
Derived from this study: PubMed 33792960Trevino JA, Novak P. TS-HDS and FGFR3 antibodies in small fiber neuropathy and Dysautonomia. Muscle Nerve. 2021 Jul;64(1):70-76. doi: 10.1002/mus.27245. Epub 2021 Apr 15.
Individual participant dataSharing planned: No

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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

Peter Novak, MD PhD principal investigator

Brigham and Women's Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regular Human Insulin in people with Type 2 Diabetes Mellitus, run by Beth Israel Deaconess Medical Center at 2 sites 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 5 inclusion and 12 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 19 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 17 Sep 2021). 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?

Gait Speed Normal Walk (cm/s). (time frame: Measured at baseline, on-treatment (V2-intervention week 1, V4 week 8, V6 week 16, V8 week 24) and post-treatment (V9-week 25, V10-week 32, V11-week 40, V12-week 48).). The study lists 4 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 NCT02415556, which also lists 8 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 19 May 2022.