Memory Aid by Intranasal Insulin in Diabetes (MemAID)

NCT02415556 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2015P0000641R01DK103902-01A1
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; Intranasal Insulin; Placebo; Memory; Gait; Non diabetic older controls

Outcome Measures

Primary Outcomes (4)

• 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 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 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 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 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).

  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).

  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).

Other Outcomes (1)

• Cerebral Blood Flow on Magnetic Resonance Imaging (MRI).

  At baseline and at V8 (week 24) the last intervention.

Study Arms (4)

Type 2 Diabetes Mellitus - Insulin

EXPERIMENTAL

40 IU of regular human insulin once daily over 24 weeks

Drug: Regular Human Insulin

Type 2 Diabetes Mellitus - Placebo

PLACEBO COMPARATOR

Intranasal sterile saline once daily over 24 weeks

Drug: Placebo

Control - Insulin

EXPERIMENTAL

40 IU of regular human insulin once daily over 24 weeks

Drug: Regular Human Insulin

Control - Placebo

PLACEBO COMPARATOR

Intranasal sterile saline once daily over 24 weeks

Drug: Placebo

Interventions

Regular Human Insulin DRUG

Regular human insulin 40 IU daily over 24 weeks

Also known as: Novolin R Novonordisk

Control - Insulin; Type 2 Diabetes Mellitus - Insulin

Placebo DRUG

Intranasal sterile saline 40 IU daily over 24 weeks

Also known as: Sterile normal saline

Control - Placebo; Type 2 Diabetes Mellitus - Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Novo Nordisk A/S: collaborator
• Medtronic: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Vera Novak

Boston, Massachusetts, 02215, United States

Location

Related Publications (8)

• 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.

  PMID: 26040423 BACKGROUND

• 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.

  PMID: 27127468 BACKGROUND

• 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.

  PMID: 25249577 BACKGROUND

• 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.

  PMID: 31923471 BACKGROUND

• 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.

  PMID: 33505777 BACKGROUND

• 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.

  PMID: 35482079 RESULT

• 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.

  PMID: 36539060 DERIVED

• 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.

  PMID: 33792960 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Vera Novak, Principal Investigator
• Organization: Beth Israel Deaconess Medical Center (BIDMC)

vnovak@bidmc.harvard.edu

6176328680

Study Officials

• Vera Novak, MD PhD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Peter Novak, MD PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Model Details: 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)

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: April 14, 2015
• Study Start: October 6, 2015
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: May 19, 2022
• Results First Posted: September 17, 2021

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)