AMPLIFI: Adaptive Modulation of Plasticity Through Lactate and Fitness Interventions

N/ANot Yet RecruitingNCT06950060

University of Alabama at Birmingham48 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Interventions

High intensity cyclingBEHAVIORAL

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.

Low-intensity cyclingBEHAVIORAL

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.

Health education sessionBEHAVIORAL

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.

Moderate Intensity Aerobic ExerciseBEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Day 2, Day 3, Day 4, and Day 5

Secondary Outcomes

Change in Long-Interval Intracortical Inhibition (LICI)

LICI is measured using a 100 ms interstimulus interval to assess GABA\<sub\>B\</sub\>-mediated inhibition. Recorded before and after each intervention session.

Time frame: Baseline, Day 5

Change in Intracortical Facilitation (ICF)

ICF is assessed using paired-pulse TMS with a 10-15 ms interstimulus interval to evaluate cortical excitability.

Time frame: Baseline, Day 5

Change in Blood Lactate Concentration

Measured via fingerstick blood samples pre-, mid-, and post-exercise.

Time frame: Day 2, Day 3, Day 4

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

Executive function neuropsychological tests.

Time frame: Day 1 and Day 5