Acute Exercise on Brain Insulin Sensitivity

Phase 2

Recruiting

• Conditions: Insulin Resistance; Aging; Cardiovascular Disease Risk; Obesity; Cognition
• Interventions: Behavioral: Exercise

• Registration Number: NCT05853913
• Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary

Dementia is a leading cause of death in the United States among aging adults. Brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. However, there is limited data available on how exercise impacts brain insulin resistance in aging. This study will test the effect of acute exercise on brain insulin sensitivity in middle-aged to older adults. The study will also examine cognition and cardiometabolic health in relation to brain insulin sensitivity.

Detailed Description

Obesity, hypertension, high blood glucose (e.g. prediabetes/type 2 diabetes), and physical inactivity is thought to worsen brain insulin resistance and reduce cerebral blood flow. This suggests lifestyle approaches may be necessary to counteract declines in brain health. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. Moreover, exercise-related structural changes in the brain, namely increased hippocampal volume, is linked to improved memory. However, there is limited data available on how exercise impacts brain insulin resistance in aging. It is also unclear if one bout of exercise may help improve brain insulin responses to insulin before fitness gains or weight loss in people at risk for dementia, type 2 diabetes and cardiovascular disease. Because single bouts of exercise are established to improve metabolic and vascular insulin sensitivity in people with obesity, the investigators anticipate exercise to raise brain insulin sensitivity in relation to cognition and cardiometabolic health.

Study Timeline

• Study First Submitted: 2023-04-19
• Study First Submitted QC: 2023-05-02
• Study Start: 2023-05-11
• Study First Posted: 2023-05-11
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-06
• Last Update Posted: 2024-08-09
• Primary Completion: 2025-04-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Male or female >40 and <80 years old.
• Has a body mass index >25 and <45 kg/m2.
• Physical Activity (<150 min of moderate/high intensity exercise per week)

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Exclusion Criteria

• Subjects who have not been weight stable (>2 kg weight change in past 3 months)
• Subjects who are smokers or who have quit smoking <1 years ago
• Subjects with abnormal estimated glomerular filtration rate (eGFR).
• Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
• Hypertensive (>160/100 mmHg)
• Subjects with a history of significant metabolic, cardiac, congestive heart failure, 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 urine pregnancy test) or nursing women
• Subjects with contraindications to participation in an exercise
• Current Pregnancy
• Currently taking active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
• Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers).
• Known contraindications for MRI imaging

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Exercise	Exercise	Individuals will exercise for at medium to hard intensity for 1 hour.

Primary Outcome Measures

Name	Time	Method
Brain insulin sensitivity	Change from baseline to exercise; about 1 week apart	MRI arterial spin labeling, cerebral blood flow

Secondary Outcome Measures

Name	Time	Method
Carbohydrate Use	Change from baseline to exercise; about 1 week apart	Indirect Calorimetry
Blood Free Fatty Acids	Change from baseline to exercise; about 1 week apart	Blood draw via colorimetric assays
Cognition	Change from baseline to exercise; about 1 week apart	NIH Toolbox Cognitive Battery
Blood Glucose	Change from baseline to exercise; about 1 week apart	Blood draw via oxidase method
Systolic and Diastolic Blood Pressure	Change from baseline to exercise; about 1 week apart	Cuff around arm

Trial Locations

Locations (4)

Institute for Food, Nutrition, and Health; 🇺🇸 New Brunswick, New Jersey, United States

Robert Wood Johnson University Hospital Clinical Research Center; 🇺🇸 New Brunswick, New Jersey, United States

Rutgers University Loree Gymnasium; 🇺🇸 New Brunswick, New Jersey, United States

Center for Advanced Human Brain Imaging Research; 🇺🇸 Piscataway, New Jersey, United States