Feasibility of Improving Glycemia With Heat Therapy to Prevent AD

NCT ID: NCT06023407

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-27
• Study Completion Date: 2027-01-01

Brief Summary

The investigators will determine if heat therapy can improve blood (Aim 1) and brain (Aim 2) glucose metabolism in cognitively healthy older adults (65+) who are at risk for AD. The investigators will also examine the degree to which changes in blood and brain glucose metabolism track together and explore several additional potential mechanisms that are critical to understanding the brain benefits of heat therapy (Aim 3). These aims will provide a comprehensive understanding of the impact of heat therapy on whole body metabolic function and brain health.

Detailed Description

Aim 1. Examine the effects of heat therapy on blood glucose regulation in older adults at risk for AD. The Investigators will determine the ability of 10 weeks of heat therapy (3 days/week) to improve blood glucose regulation in older adults at risk for AD. Our primary outcome measures will be change in glycated hemoglobin (HbA1c), and change in insulin sensitivity index (ISI) assessed pre- vs post-intervention. The Investigators will also perform continuous glucose monitoring for 7 days prior to and following the intervention, as well as monitor dietary patterns during the intervention. The Investigators hypothesize that 10 weeks of heat therapy will lower HbA1c values and improve ISI outcomes.

Aim 2. Test the effect of heat therapy on brain glucose metabolism. To date, no studies have examined the impact of heat therapy on brain glucose metabolism. Here The Investigators will determine the effect of 10 weeks of heat therapy on brain glucose metabolism in older adults at risk for AD. Our primary outcome measure will be change in [18F] fluorodeoxyglucose (FDG) global standardized uptake value ratio (SUVR) pre- vs post- heat therapy. The Investigators hypothesize that individuals will improve (increase) global cerebral glucose metabolism following 10 weeks of heat therapy. The Investigators further hypothesize that the degree of change in blood glucose metabolism will track with change in brain glucose metabolism.

Aim 3. Explore the effect of heat therapy on fluid biomarkers (proteostasis, inflammation, neuropathology) and neuroimaging markers of brain health. The Investigators will explore the effect of heat therapy on plasma markers of proteostasis (HSP's), inflammation (CRP, TNF, IL-6, JNK and IKK) and AD-related neuropathology (Amyloid/Tau/Neurodegeneration; A/T/N measures) markers in plasma at baseline and following 10 weeks of heat treatment. The Investigators will also obtain MRI measures of resting state metabolism, brain blood flow, and oxygen uptake for preliminary characterization of intervention-related changes. The Investigators hypothesize that proteostasis, inflammation, and AD neuropathology will be beneficially affected by heat treatment. The Investigators further hypothesize that the team will observe benefits in MRI-related brain outcomes.

Conditions

Healthy Aging; Alzheimer Disease; Metabolic Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Heat therapy Group

40.5°C water

Group Type: EXPERIMENTAL

Water Immersion Heat Therapy

Intervention Type: OTHER

10-weeks of 3 days per week in 1 of the 2 arms

Thermoneutral Control Group

36°C water

Group Type: SHAM_COMPARATOR

Water Immersion Heat Therapy

Intervention Type: OTHER

10-weeks of 3 days per week in 1 of the 2 arms

Interventions

Water Immersion Heat Therapy

10-weeks of 3 days per week in 1 of the 2 arms

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 65 and older
• Stable medication doses (>1 month)
• Post-menopausal
• Clinical Dementia Rating (CDR) of 0
• History of or current metabolic impairment (i.e. metabolic syndrome, pre-diabetes, Type 2 Diabetes, etc)

Exclusion Criteria

• Excluded from or unable to complete an MRI scan. MRI compatible pacemakers will require cardiologist clearance prior to enrolling.
• ACSM Risk score stratification of "High" unless cleared by a physician prior to participation.
• Myocardial infarction or symptoms of coronary artery disease in the last 2 years.
• History of or current diagnosis of disorders with the potential to impair cognition (i.e. AD, Parkinson's disease, stroke (defined as clinical episode w/ neuroimaging evidence in appropriate area to explain symptoms)).
• Insulin-dependent (Type 1) Diabetes Mellitus.
• Clinically significant chronic disease such as cancer, HIV, or acquired immunodeficiency syndrome.
• Clinically significant depressive symptoms that may impair cognition, use of psychoactive and investigational medications, and significant visual or auditory impairment.
• Orthopedic complications that would preclude individuals from safely entering a hot tub.
• Untreated hypothyroidism or diseases associated with heat intolerance (i.e. Graves disease, etc).
• Contraindication for temperature pill ingestion (i.e. inflammatory bowel disease, diverticulitis or related).

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jill Morris

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

Univeristy of Kansas Medical Center

Kansas City, Kansas, United States

Countries

United States

Other Identifiers

R01AG081304

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00147285

Identifier Type: -

Identifier Source: org_study_id