AMPLIFI: Adaptive Modulation of Plasticity Through Lactate and Fitness Interventions

NCT06950060 | Not Yet Recruiting DMC

• 1 other identifier: IRB-300014361
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The AMPLIFI study (Adaptive Modulation of Plasticity through Lactate and Fitness Interventions) investigates how short-term aerobic exercise influences brain plasticity and learning in older adults and stroke survivors. The study compares three groups: one performing aerobic cycling at an intensity that elevates lactate levels, one performing low-intensity exercise, and one receiving health education without exercise. All participants will complete motor learning tasks and undergo brain-stimulation testing using transcranial magnetic stimulation (TMS) to assess how well the brain responds to training. The goal is to understand whether different types of exercise can improve brain function, movement, and memory, and how the body's response to exercise (like lactate levels) might support brain health. This research may help identify low-cost, non-invasive interventions-such as targeted exercise-that improve motor and cognitive outcomes in aging and stroke recovery.

Conditions

Cognitive Decline; Motor Dysfunction; Aging; Neuroplasticity; Stroke, Chronic

Keywords

Transcranial Magnetic Stimulation (TMS); Cortical Inhibition; Neuroplasticity; Aerobic Exercise; Motor Learning; Aging; Stroke Rehabilitation; Cortical Excitability; GABAergic Inhibition

Outcome Measures

Primary Outcomes (1)

• Motor Learning Performance (12-Digit Serial Reaction Time Task)

  Motor learning is assessed using the 12-digit Serial Reaction Time Task (SRTT), a computer-based measure of implicit motor sequence learning. Participants respond to visual cues by pressing buttons in a fixed or random sequence. Learning is quantified by changes in reaction time and accuracy across structured and unstructured trials. A learning index is derived by comparing performance between patterned (learning) and random sequences.

  Baseline, Day 2, Day 3, Day 4, and Day 5

Secondary Outcomes (4)

• Change in Long-Interval Intracortical Inhibition (LICI)

  Baseline, Day 5

• Change in Intracortical Facilitation (ICF)

  Baseline, Day 5

• Change in Blood Lactate Concentration

  Day 2, Day 3, Day 4

• Change in Executive Function (D-KEFS Verbal Fluency and Stroop Tests)

  Day 1 and Day 5

Study Arms (4)

Aerobic Exercise at Lactate Threshold

EXPERIMENTAL

Participants complete a 20-minute aerobic cycling session at individually prescribed intensity to achieve lactate threshold, based on VO2 max and blood lactate data. This condition is designed to induce metabolic stress and engage neuromodulatory pathways related to cortical plasticity. Participants complete TMS and motor learning tasks before and after the intervention.

Behavioral: High intensity cycling

Low-Intensity Aerobic Exercise

ACTIVE COMPARATOR

Participants complete a 20-minute cycling session at a light workload, below lactate threshold. This condition controls for movement and engagement without significant metabolic challenge. TMS and motor learning outcomes are assessed pre- and post-intervention.

Behavioral: Low-intensity cycling

Education Control

PLACEBO COMPARATOR

Participants engage in a 20-minute health education session instead of exercise. This arm serves as a non-exercise control to isolate the effects of physical exertion on neuroplasticity. All outcome measures are collected similarly to the exercise groups.

Behavioral: Health education session

Active Comparator: Moderate-Intensity Aerobic Exercise

ACTIVE COMPARATOR

Arm Description: Participants complete a 20-minute cycling session at a moderate workload, surrounding lactate threshold. This condition controls for movement and engagement without advanced metabolic challenge. TMS and motor learning outcomes are assessed pre- and post-intervention.

Behavioral: Moderate Intensity Aerobic Exercise

Interventions

Health education session BEHAVIORAL

Participants receive a 20-minute session of health education content (e.g., wellness, healthy aging). No exercise is performed. Participants undergo TMS and motor learning testing before and after the session. This condition is used to control for attention and cognitive engagement without physical activity.

Also known as: Education

Education Control

High intensity cycling BEHAVIORAL

Participants cycle on a stationary ergometer at an intensity prescribed to reach their lactate threshold, guided by VO2 max results and lactate sampling. The session lasts approximately 20 minutes and is preceded and followed by TMS assessments and a structured motor learning task. This condition is designed to evaluate the effect of exercise-induced metabolic stress on cortical inhibition and motor learning.

Also known as: HIIT

Aerobic Exercise at Lactate Threshold

Low-intensity cycling BEHAVIORAL

Participants perform 20 minutes of cycling at a light workload below their lactate threshold. Exercise intensity is individualized using heart rate and perceived exertion (Borg RPE scale), avoiding significant metabolic activation. TMS and motor learning are assessed pre- and post-exercise. This condition serves as an active comparator to assess the impact of exercise intensity.

Also known as: MICT

Low-Intensity Aerobic Exercise

Moderate Intensity Aerobic Exercise BEHAVIORAL

Participants cycle on a stationary ergometer at an intensity prescribed to surround, but not exceed their lactate threshold, guided by VO2 max results and lactate sampling. The session lasts approximately 20 minutes and is preceded and followed by TMS assessments and a structured motor learning task. This condition is designed to evaluate the effect of moderate exercise-induced metabolic stress on cortical inhibition and motor learning.

Active Comparator: Moderate-Intensity Aerobic Exercise

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For All Participants:
• Able to provide informed consent
• Right-handed (for TMS consistency)
• English-speaking
• Clearance for moderate-intensity aerobic exercise
• Able to safely sit and pedal a stationary cycle ergometer
• No contraindications to TMS (e.g., no metal in skull, pacemakers, or seizure history)
• Younger Adults (18-35):
• No history of neurological or psychiatric conditions
• Not currently on medications that affect the central nervous system
• Older Adults (60-85):
• No diagnosis of dementia
• Independent in activities of daily living
• No stroke history
• Stroke Survivors (40-85):

You may not qualify if:

• History of epilepsy or seizures
• Current substance abuse or uncontrolled psychiatric disorder
• Severe cardiovascular disease or unstable medical condition
• Pregnancy
• Contraindications to TMS or exercise testing (e.g., implanted neurostimulators, severe hypertension)
• Participation in another interventional trial within the past 30 days

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

CH19 933 19th St S

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Stroke; Bronchiolitis Obliterans Syndrome; Cognitive Dysfunction; Neurologic Manifestations

Interventions

Educational Status

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Socioeconomic Factors; Population Characteristics

Study Officials

• Keith McGregor, PhD

  Keith McGregor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keith M McGregor, PhD

CONTACT

‪(205) 693-9997‬; kmmcgreg@uab.edu

Ayat Najmi, BS

CONTACT

2059346030; anajmi@uab.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Director of Research

Model Details: Participants are randomized into one of four parallel groups: (1) aerobic exercise at lactate threshold, (2) moderate intensity exercise, (3) low-intensity aerobic exercise, or (4) education-only control. Outcomes are assessed at multiple time points to examine changes in cortical inhibition, motor performance, and cognitive function.

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 29, 2025
• Study Start (Estimated): May 14, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)