Recruiting
Phase 2
Phase 3

Aerobic Exercise & Intranasal Insulin

Sponsor:

Rutgers, The State University of New Jersey

Code:

NCT07675499

Conditions

Type 2 Diabetes

Insulin Sensitivity/Resistance

Cognition

Brain Blood Flow

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Interventions

Intranasal Insulin

Intranasal Placebo

High Intensity Exercise

Study Details

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

Study ID

NCT07675499

Start date

Aug 3, 2026

Status verified date

Jun, 2026

Completion date

May 31, 2029

Anticipated

Primary completion date

May 18, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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:

  • History of head trauma or neurosurgery, or neurological disorder (other than headaches or peripheral nerve disease) as these may impact neuroimaging results.
  • Ferrous material implanted in or on the body, including flakes or filings, surgical clips, bullets, or electrical devices such as a pacemaker, or nonremovable ferrous jewelry (fillings in teeth and permanent retainers are permitted).
  • Fillings and permanent retainers do not provide a safety risk and are not general exclusions. However, upper retainers may cause artifacts in ventral frontal regions and therefore may be an exclusion for some studies.
  • Individuals with surgical pins or plates above the neck are excluded. Surgical pins or plates below the neck are exclusions, except when the material is fixed to bone, and considered acceptable by the Reference Manual for Magnetic Resonance Safety. Implants and Devices, 2020 Edition. Almost all recent orthopedic implants are made of materials that are not ferromagnetic and therefore are safe for scanning, and even though some screws are still made of ferromagnetic materials these are firmly screwed into bone. In cases where the material is unknown or deemed unsafe for scanning by the Reference Manual for Magnetic Resonance Safety. Implants and Devices the participant will be excluded.
  • History of eye injury involving metallic materials, shavings in eyes, or welding without a face mask
  • Lead/iron tattoos
  • Claustrophobia (history of significant anxiety in closed places).
  • Back problem that would prevent the subject from laying still comfortably for up to 90 minutes.
  • Deafness

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: HiEx with Intranasal Placebo

active comparator: HiEx with Intranasal Insulin

Interventions

Intranasal Insulin

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.

Intranasal Placebo

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

High Intensity Exercise

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.

Primary outcome measure

  • Cerebrovascular Insulin Sensitivity [ Time Frame: Change from baseline to the end of the intervention at 16 weeks ]

Central Contacts and Locations

Central contacts

Steven K Malin, PhD

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

Emily M Heiston, PhD

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

Locations

Robert Wood Johnson University Hospital Clinical Research Center

Recruiting

New Brunswick, New Jersey, United States, 08091

Contacts

Fei Chen

732-235-5966chenf2@rwjms.rutgers.edu

Institute for Food, Nutrition, and Health

Recruiting

New Brunswick, New Jersey, United States, 08901

Contacts

Sue Shapses, PhD

shapses@rutgers.edu

Rutgers University Loree Gymnasium

Recruiting

New Brunswick, New Jersey, United States, 08901

Contacts

Steven Malin, PhD

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

Center for Advanced Human Brain Imaging Research

Recruiting

Piscataway, New Jersey, United States, 08854

Contacts

David Zald, PhD

732-235-7211dz268@rbhs.rutgers.edu

More Information

Sponsor

Rutgers, The State University of New Jersey

Last update posted

Jun 30, 2026

Last verified

Jun, 2026

Keywords

  • Exericse
  • Intranasal Insulin

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Rutgers, The State University of New Jersey on 2026-06-30.