Lactate for Energy and Neurocognition

NCT05207397 | Completed DMC

• 2 other identifiers: STUDY001443031R01AG062548
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Improved cardiorespiratory fitness following an aerobic exercise program elicits cognitive benefit in elderly subjects and memory improvement in Alzheimer's disease (AD). The physiological mechanism may be related to exercise-mediated change in circulating factors that permeate the brain. The response to each individual bout of exercise (i.e. the acute exercise response) may differ between subjects and be key to driving brain benefit. In young populations, the acute response to exercise can last hours and affect brain glucose metabolism. However, the field knows little about this acute exercise response in AD. Most exercise intervention trials designed to prevent and slow AD assess biomarkers at two fasting time points: pre- and post-intervention. The acute exercise response in the brain and periphery likely varies between subjects and diagnoses and provide key information regarding mechanisms of benefit. Our primary goals are to characterize the acute exercise response to exercise in the brain (glucose metabolism) and periphery (biomarker response) in aging and AD. We will identify relationships between exercise-related factors (i.e. heart rate, biomarkers) and change in brain metabolism and cognition. Understanding these mechanistic relationships will provide specific targets that can be used in future trials to develop individualized exercise prescriptions and maximize benefit.

Conditions

Healthy Aging; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Metabolic Clearance Rate (MCR)

  units of lactate cleared per minute (mg/kg×min)

  2 hours

Secondary Outcomes (1)

• Cognitive Performace

  2 hours

Study Arms (2)

Healthy Control

Lactate clamp: After insertion of the catheters, and prior to isotope infusion, a background blood and breath sample (ParvoMedics TrueOne 2400) will be obtained. The investigator will then administer priming doses of 57.5 mg \[13C3\]lactate, 250 mg D2-glucose and 136 mg H13CO3- followed by continuous infusions of \[13C3\]lactate at 10 mg/min and D2-glucose at 2 mg/min. Along with the continuous isotope infusion the investigator will begin infusion of the Na-lactate at approximately 2.6mg/kg·min. Based upon readings from blood samples during the infusion, this rate will be adjusted as needed to maintain the target lactate concentration of approximately 4-5 mM. Blood samples will be drawn at 10, 20, 30, 45, 60, 75, 90 and 120 minutes, while breath samples will be collected at 60, 75, 90 and 120 minutes.

Other: Lactate infusion

Mild Cognitive Impairment

Lactate clamp: After insertion of the catheters, and prior to isotope infusion, a background blood and breath sample (ParvoMedics TrueOne 2400) will be obtained. The investigator will then administer priming doses of 57.5 mg \[13C3\] lactate, 250 mg D2-glucose and 136 mg H13CO3- followed by continuous infusions of \[13C3\] lactate at 10 mg/min and D2-glucose at 2 mg/min. Along with the continuous isotope infusion the investigator will begin infusion of the Na-lactate at approximately 2.6mg/kg·min. Based upon readings from blood samples during the infusion, this rate will be adjusted as needed to maintain the target lactate concentration of approximately 4-5 mM. Blood samples will be drawn at 10, 20, 30, 45, 60, 75, 90 and 120 minutes, while breath samples will be collected at 60, 75, 90 and 120 minutes.

Other: Lactate infusion

Interventions

Lactate infusion OTHER

The unlabeled lactate infusion cocktail (30% L(+)-lactic acid solution (Sigma) with 2N NaOH, pH4.8) and stable isotope infusions were made by a pharmacy and tested to be sterile and pyrogen free. Upon arriving to the KU Clinical and Translational Science Unit, a catheter will be placed in the subject's hand, which will be placed into a heated hand box for collection of arterialized blood. A second catheter will be placed in the opposing forearm vein for the infusion of lactate isotope solution and unlabeled lactate infusion cocktail. After insertion of the catheters, and prior to isotope infusion, a background blood and breath sample (ParvoMedics TrueOne 2400) will be obtained. We will then administer priming doses of 57.5 mg \[13C3\]lactate, 250 mg D2-glucose and 136 mg H13CO3- followed by continuous infusions of \[13C3\]lactate at 10 mg/min and D2-glucose at 2 mg/min \[53\]. Along with the continuous isotope infusion we will begin infusion of the Na-lact

Healthy Control; Mild Cognitive Impairment

Eligibility Criteria

• Age: 60 Years - 95 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The investigator will leverage the KU ADC Outreach and Recruitment (OR) Core, which reaches more than 2000 individuals annually. The OR Core supports and maintains Eligibility Database, which contains demogrpahic and health information for all individuals who contact the ADC or are referred from clinic (n\>7000, \~5000 without cognitive complaints). Recruitment will also leverage the ADC Clinical Cohort, which is comprised of 400 individuals who are characterized annually with clinical and cognitive testing.

You may qualify if:

• Age 60 and older
• Stable medication doses (\>1month)
• Post-menopausal
• Diagnosis of either Nondemented (CDR 0) or Probable AD (CDR 0.5 or 1 only)

You may not qualify if:

• Inability to provide consent
• Diagnosis of insulin-dependent (Type 1) Diabetes Mellitus
• Anti-platelet medication (Plavix), Warfarin, and other anticoagulants (Eliquis, Pradaxa, and Xarelto)
• Recent ischemic heart disease (\<2 years)
• Diagnosis of a clinically significant chronic disease including CVD, other metabolic diseases (e.g., thyroid), cancer, HIV, or acquired immunodeficiency syndrome
• Any Neurological disorders that have the potential to impair cognition or brain metabolism (e.g., Parkinson's disease, stroke defined as a clinical episode with neuroimaging evidence in an appropriate area to explain the symptoms).
• Clinically significant depressive symptoms that may impair cognition, abnormalities in B12, RPR, or thyroid function that may impair cognition, use of psychoactive and investigational medications, and significant visual or auditory impairment

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Univeristy of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Related Publications (1)

• Kemna RE, Kueck PJ, Blankenship AE, John CS, Johnson CN, Green ZD, Chamberlain T, Thyfault JP, Mahnken JD, Miller BF, Morris JK. Methods to characterize lactate turnover in aging and Alzheimer's disease; The LEAN study. Contemp Clin Trials. 2024 Nov;146:107682. doi: 10.1016/j.cct.2024.107682. Epub 2024 Sep 3.

  PMID: 39236780 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, plasma

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jill Morris

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: January 26, 2022
• Study Start: April 12, 2023
• Primary Completion: March 29, 2024
• Study Completion: March 29, 2024
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)