Exercise and Intranasal Insulin in Type 2 Diabetes

ConditionsType 2 Diabetes Insulin Sensitivity/Resistance Cognition Brain Blood Flow

Trial statusRecruiting

Trial phasePhase 2, Phase 3

Trial typeInterventional

Biological sexAll

Age55-80

SponsorRutgers, The State University of New Jersey

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

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

Treatment groups

60 Participants

are divided into 2 treatment groups

Group A: HiEx with Intranasal PlaceboPlacebo comparator 2 interventions

Group B: HiEx with Intranasal InsulinActive comparator 2 interventions

Trial outcomes

Primary outcomes

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).

Time frame