AMPLIFI: Adaptive Modulation of Plasticity Through Lactate and Fitness Interventions
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- Motor Learning Performance (12-Digit Serial Reaction Time Task)
Study Overview
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.
Detailed Description
The AMPLIFI study is a mechanistic clinical trial designed to investigate the neurophysiological effects of acute aerobic exercise on cortical plasticity and motor learning in older adults and individuals with chronic stroke. Participants are randomized into one of three groups: (1) moderate-to-high intensity aerobic exercise at lactate threshold, (2) moderate intensity aerobic exercise, (3) low-intensity aerobic exercise, or (4) education-only control.
The primary outcome measure is cortical inhibition, assessed using transcranial magnetic stimulation (TMS) measures including short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF). Secondary outcomes include performance on upper extremity motor tasks, measures of verbal and executive function, and blood lactate levels.
Participants complete three sessions over 2-3 weeks, including baseline assessments, VO2 max testing, multiple blood draws, and cognitive and motor testing. The exercise intervention is delivered via stationary cycling at intensities tailored using individual VO2 max data and lactate monitoring. Genetic and biochemical assays will be performed on blood samples to explore associations between metabolic and neural response.
This study will clarify how lactate-related exercise intensity impacts cortical inhibition and whether those effects support improvements in motor learning. Findings may help define the mechanisms by which exercise promotes neuroplasticity and support individualized rehabilitation strategies for aging and post-stroke populations.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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):
- •At least 6 months post-stroke (chronic phase)
- •Medically stable and cleared for aerobic exercise
- •Able to engage in motor learning task (with or without hemiparetic adaptations)
Exclusion Criteria
- •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
Arms & Interventions
Low-Intensity Aerobic Exercise
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.
Intervention: Low-intensity cycling (Behavioral)
Education Control
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.
Intervention: Health education session (Behavioral)
Aerobic Exercise at Lactate Threshold
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.
Intervention: High intensity cycling (Behavioral)
Active Comparator: Moderate-Intensity Aerobic Exercise
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.
Intervention: Moderate Intensity Aerobic Exercise (Behavioral)
Outcomes
Primary Outcomes
Motor Learning Performance (12-Digit Serial Reaction Time Task)
Time Frame: Baseline, Day 2, Day 3, Day 4, and Day 5
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.
Secondary Outcomes
- Change in Executive Function (D-KEFS Verbal Fluency and Stroop Tests)(Day 1 and Day 5)
- 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)
Investigators
Keith McGregor
Associate Professor, Director of Research
University of Alabama at Birmingham