Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
289 participants
INTERVENTIONAL
2015-10-06
2020-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
IN Insulin in Type 1 Diabetes (T1D) Hypoglycemia Unawareness: Safety Only Phase
NCT04028960
SNIFF Multi-Device Study 2
NCT04199767
Measurement of Insulin Levels in the Cerebrospinal Fluid of Healthy Adults After a Single Intranasal Dose - Middle Age
NCT06434038
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
NCT00419562
InsuLearn Feasibility With Type 1 Diabetes Patients Under MDI Therapy
NCT06411548
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
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)
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Type 2 Diabetes Mellitus - Insulin
40 IU of regular human insulin once daily over 24 weeks
Regular Human Insulin
Regular human insulin 40 IU daily over 24 weeks
Type 2 Diabetes Mellitus - Placebo
Intranasal sterile saline once daily over 24 weeks
Placebo
Intranasal sterile saline 40 IU daily over 24 weeks
Control - Insulin
40 IU of regular human insulin once daily over 24 weeks
Regular Human Insulin
Regular human insulin 40 IU daily over 24 weeks
Control - Placebo
Intranasal sterile saline once daily over 24 weeks
Placebo
Intranasal sterile saline 40 IU daily over 24 weeks
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Regular Human Insulin
Regular human insulin 40 IU daily over 24 weeks
Placebo
Intranasal sterile saline 40 IU daily over 24 weeks
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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 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.
50 Years
85 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Novo Nordisk A/S
INDUSTRY
Medtronic
INDUSTRY
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Beth Israel Deaconess Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Vera Novak
Associate Professor of Neurology
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Vera Novak, MD PhD
Role: PRINCIPAL_INVESTIGATOR
Beth Israel Deaconess Medical Center
Peter Novak, MD PhD
Role: PRINCIPAL_INVESTIGATOR
Brigham and Women's Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Vera Novak
Boston, Massachusetts, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
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.
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.
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.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2015P000064
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.