Exercise and Intranasal Insulin in Type 2 Diabetes

NCT07675499 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro20260007511R01DK147509-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

About 6.5 million adults in the United States who are 65 or older have dementia. While the exact cause of dementia is not known, it may be due to changes in the brain. Further, risk may be higher when the brain does not respond to insulin. Indeed, brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise may help reduce the risk of dementia by increased blood flow to the brain and help the brain respond better to insulin. In addition, giving insulin through a nose spray (called intranasal insulin) may also help with thinking and memory. However, it is unknown if using both exercise and intranasal insulin is best for the brain.

Conditions

Type 2 Diabetes; Insulin Sensitivity/Resistance; Cognition; Brain Blood Flow

Keywords

Exericse; Intranasal Insulin

Outcome Measures

Primary Outcomes (1)

• Cerebrovascular Insulin Sensitivity

  People will undergo a motion corrected diffusion weighted gradient-and spin echo pseudo-Continuous Arterial Spin Labeling (pCASL) sequence with 5 post labelling delays. This provides 3.5 mm3 resolution for whole brain coverage for CBF. CBF will be determined via the hippocampus. Participants will then be administrated INI at a dose of 40 IU of human insulin (0.4 ml, Humulin, Eli Lilly \& Co., Indianapolis, IN). Single puffs of 0.1ml will occur 4 times (twice each nostril) over 2 minutes via the VianaseTM electronic atomizers (Kurve Technology Inc., Lynnwood, WA). After 30 minutes, scanning will be repeated to determine CBF changes to indicate brain insulin sensitivity. Brain insulin sensitivity will be defined as the change from fasting to INI (e.g. CBFINI - CBFfast).

  Change from baseline to the end of the intervention at 16 weeks

Secondary Outcomes (7)

• Blood Brain Barrier Integrity

  Change from baseline to the end of the intervention at 16 weeks

• Insulin Signaling Proteins

  Change from baseline to the end of the intervention at 16 weeks

• Augmentation Index

  Change from baseline to the end of the intervention at 16 weeks

• Peripheral Insulin Sensitivity

  Change from baseline to the end of the intervention at 16 weeks

• Cognitive Function

  Change from baseline to the end of the intervention at 16 weeks

Study Arms (2)

HiEx with Intranasal Placebo

PLACEBO COMPARATOR

Drug: Intranasal Placebo; Behavioral: High Intensity Exercise

HiEx with Intranasal Insulin

ACTIVE COMPARATOR

Drug: Intranasal Insulin; Behavioral: High Intensity Exercise

Interventions

Intranasal Insulin DRUG

Dosage will be 20 IU of INI twice per day (40 IU in total/day). The study will use the Kurve Technology intranasal device, which delivers a 20 second stream of insulin through a nose piece into a nostril, after which the device switches off. The process will then be repeated in the other nostril.

HiEx with Intranasal Insulin

Intranasal Placebo DRUG

Saline will be administered twice daily (20 seconds in each nostril) using the Kurve Technology intranasal insulin device.

HiEx with Intranasal Placebo

High Intensity Exercise BEHAVIORAL

High intensity exercise will consist of 16 weeks of walking at \~85% of each participant's predetermined VO2max and monitored via heart rate. Supervised exercised will occur on a treadmill 3d/wk. The duration of each exercise session will be adjusted based on fitness level so that \~300 kcal will be expended per training session during weeks 1-2, 350 kcal per training session during weeks 3-4, and 400 kcal per training session during weeks 5-16. This usually equals \~60 minutes per session but can vary from person to person. Each session will start with a 5-minute warm-up and end with a 5-minute cool down. During each exercise session, individuals will wear a heart rate monitor rating of perceived exertion will be recorded.

HiEx with Intranasal Insulin; HiEx with Intranasal Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 55-80 years old
• Type 2 diabetes diagnosis or confirmation HbA1c \>6.5% and fasting glucose \>126 mg/dl
• Individuals prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors \>6 months.
• MOCA ≥26
• Body mass index (BMI) ≥25 and ≤40 kg/m2
• Not diagnosed with Type 1 diabetes
• Not currently engaged in \<90 min/wk of exercise

You may not qualify if:

• A diagnosis of dementia
• Neurologic disease (e.g. Parkinson's, autonomic neuropathy, etc.)
• Intolerance to insulin
• Morbidly obese patients (BMI \>40 kg/m2) and lean patients (BMI \<25 kg/m2)
• \>2 kg weight change in past 6 months
• Participants who have been recently active (\>90 min of moderate/high intensity exercise)
• Individuals who are smokers or who have quit smoking (\<2 years)
• Hypertriglyceridemia (400 mg/dl) and hypercholesterolemic (\>260 mg/dl) subjects
• Uncontrolled Hypertensive (\>160/100 mmHg)
• Participants with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety
• Pregnant (as evidenced by positive pregnancy test) or nursing women
• Participants with contraindications to participation in an exercise training program
• Major psychiatric disorders (e.g. psychosis, bipolar disorder, major depression, alcohol/substance abuse)
• History of head trauma or loss of consciousness in last 5 years.
• Known contraindications for MR imaging:

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (4)

Robert Wood Johnson University Hospital Clinical Research Center

New Brunswick, New Jersey, 08091, United States

RECRUITING

Institute for Food, Nutrition, and Health

New Brunswick, New Jersey, 08901, United States

RECRUITING

Rutgers University Loree Gymnasium

New Brunswick, New Jersey, 08901, United States

RECRUITING

Center for Advanced Human Brain Imaging Research

Piscataway, New Jersey, 08854, United States

RECRUITING

Related Publications (4)

• Malin SK, Battillo DJ, Beeri MS, Mustapic M, Kapogiannis D. A Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle-Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk. Compr Physiol. 2026 Apr;16(2):e70131. doi: 10.1002/cph4.70131.

  PMID: 41876945 BACKGROUND

• Malin SK, Battillo DJ, Zald DH, Ramirez J. Appetite Perception and Cerebral Blood Flow in Aging Adults Following a Single Bout of Exercise. Nutrients. 2026 Mar 27;18(7):1072. doi: 10.3390/nu18071072.

  PMID: 41978122 BACKGROUND

• Malin SK, Zald DH, Battillo D. Acute Exercise Reduces Intranasal Insulin-Mediated Elevations in Blood Pressure in Aging Adults with Cardiometabolic Risk. Am J Physiol Regul Integr Comp Physiol. 2026 Jun 15. doi: 10.1152/ajpregu.00119.2026. Online ahead of print.

  PMID: 42295834 BACKGROUND

• Malin SK, Battillo DJ, Beeri MS, Mustapic M, Delgado-Peraza F, Kapogiannis D. Two weeks of exercise alters neuronal extracellular vesicle insulin signaling proteins and pro-BDNF in older adults with prediabetes. Aging Cell. 2025 Jan;24(1):e14369. doi: 10.1111/acel.14369. Epub 2024 Oct 18.

  PMID: 39421964 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

High-Intensity Interval Training

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Steven K Malin, PhD

  Rutgers University - New Brunswick

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven K Malin, PhD

CONTACT

848-932-7540; steven.malin@rutgers.edu

Emily M Heiston, PhD

CONTACT

848-932-7540; emily.heiston@rutgers.edu

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: Professor

Model Details: Participants will be randomly assigned to receive high intensity exercise training with intranasal insulin or high intensity exercise training with intranasal placebo.

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 30, 2026
• Study Start (Estimated): August 3, 2026
• Primary Completion (Estimated): May 18, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)