Aphasia Physical EXercise Study: Randomized Trial (APEX)

High-intensity Exercise in Stroke Recovery: Randomized Trial

The goal of this clinical trial is to evaluate the effects of a high-intensity exercise program on recovery in individuals with post-stroke aphasia. The high-intensity exercise program has been specifically designed for individuals with post-stroke aphasia and includes an interval training full-body workout, which can increase cardiovascular fitness, improve muscle strength and motor performance, and maximize cognitive and language gains. The main question this study aims to answer is:

• Does participation in a high-intensity exercise program lead to changes in physical health, language, cognitive, motor recovery, psychological and/or psychosocial domains?

Participants will be randomly assigned to either a high-intensity exercise program (target intervention) or a low-intensity exercise program (control intervention) delivered over 12-weeks in a group setting.

Outcome measures will be collected once immediately after the intervention period and once during the following 12-week maintenance period to capture short- and long-term effects of the exercise program.

Study Overview

• Status: Recruiting
• Conditions: Aphasia; Aphasia, Acquired; Aphasia Following Cerebral Infarction; Aphasia, Non-fluent; Aphasia, Fluent; Aphasia Following Nontraumatic Intracerebral Hemorrhage
• Intervention / Treatment: Behavioral: High-intensity physical exercise; Behavioral: Low-intensity physical exercise

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Ivanova, PhD; Phone Number: 650-390-7572; Email: ivanova@berkeley.edu

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94720
      • Recruiting
      • University of California, Berkeley
      • Contact: Maria Ivanova, PhD; Phone Number: 650-390-7572; Email: ivanova@berkeley.edu
    • Hayward, California, United States, 94542
      • Recruiting
      • California State University, East Bay
      • Contact: Michelle Gravier, PhD; Email: michelle.gravier@csueastbay.edu
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Cathra Halabi, MD; Email: Cathra.Halabi@ucsf.edu
    • San Francisco, California, United States, 94118
      • Recruiting
      • University of San Francisco
      • Contact: Christian J Thompson, Ph.D.; Email: cjthompson@usfca.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aphasia following ischemic or hemorrhagic stroke
• Aphasia as determined by a standardized language test (Western Aphasia Battery Aphasia Quotient < 93.8 at study intake)
• At least 6 months from the last stroke
• Proficient in English before the stroke
• At least 8 years of education
• Between the ages of 18 and 80
• Independent with ambulation without a device (single-point cane accepted)
• Medically stable with no contraindications to participate in regular physical exercise as determined by the patients' own primary care provider or other treating provider.

Exclusion Criteria:

• Prior history of dementia, neurologic illness (other than stroke), or recent (last 3 years) substance abuse
• Significant visual or hearing disabilities (e.g., neglect, uncorrected visual or hearing loss) that interfere with testing
• Self-report uncontrolled cardiorespiratory and/or metabolic disorders incompatible with exercise

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-intensity physical exercise; The participants will take part in a high-intensity Aphasia Physical EXercise (APEX) intervention designed specifically for individuals with chronic post-stroke aphasia for 12 weeks.	Behavioral: High-intensity physical exercise; We have developed a new exercise program specifically designed for individuals with post-stroke aphasia, Aphasia Physical EXercise (APEX), to provide a safe, stroke- and aphasia-friendly physical exercise intervention to achieve optimal physical fitness and cognitive/language gains. This intervention, based on published research and clinical practice recommendations, is a high-intensity interval training full-body workout optimized to accommodate the range of motor abilities and general deconditioning observed in stroke survivors.
Active Comparator: Low-intensity physical exercise; The participants will participate in a low-intensity non-aerobic exercise program for 12 weeks.	Behavioral: Low-intensity physical exercise; As an active control intervention, a low-intensity non-aerobic exercise program was selected that mirrors more closely the standard-of-care physical therapy currently provided to stroke patients. This control intervention will offer the same level of participant involvement and type of interaction, but without the intensity element, i.e., it will not incorporate the cardiovascular and the strengthening components.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change on the Western Aphasia Battery (WAB) - Aphasia Quotient	The Aphasia Quotient from the Western Aphasia Battery (a standardized language test) measures overall severity of language impairment in aphasia and ranges from 0 to 100, with lower scores indicative of more severe aphasia.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change on the WAB subtest scores	The subtests from the Western Aphasia Battery (a standardized language test) measure different language capacities. Specifically, we will look at Spontaneous Speech, Fluency, Auditory Verbal Comprehension, Repetition, Naming and Word Finding subtest scores.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change on the Curtiss-Yamada Comprehensive Language Evaluation - Revised (CYCLE-R)	A sentence-to-picture matching tasks that evaluates comprehension of sentences of varying complexity. The scores range from 0 to 100%, with higher scores indicative of better comprehension abilities.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on Category and Letter Verbal Fluency tasks	Test of word retrieval and executive control abilities such as updating, shifting, and inhibiting. Participants are asked to name as many items as possible in 1 minute for a given category (e.g., clothes) and for a given letter (e.g., "s").	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change on the Philadelphia Naming Test (PNT)	Aphasia naming test to assess word retrieval abilities. The score ranges from 0 to 100, with a higher score indicating greater naming ability.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on the California Cognitive Assessment Battery (CCAB)	This is a computerized assessment battery of cognitive tasks that provides a comprehensive assessment of different cognitive domains. These tasks include computerized version of standard cognitive tasks such as Trail making test, Stroop test, Digit and Spatial Span tasks, Verbal learning tasks. These tasks will require participants to memorize lists of words, digits, describe pictures, and draw on the tablet. Participant's verbal and pointing responses will be recorded. The following tasks will be used: BAVLT Encoding, Digit Span Forward, Digit Span Reverse, Picture Matching, Spatial Span, Finger Tapping, BAVLT Delayed Recall, Continuous Picture Naming, Picture Description, Simple Reaction Time, Trails A, Trails B, Stroop, Design Fluency, Picture Description Delayed Recall, Verbal Fluency.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes in Maximal Aerobic Capacity	This is a measure of cardiorespiratory and metabolic fitness. Maximal Aerobic Capacity (VO2 Max) is the ability of the body to utilize oxygen to produce energy and is measured via a graded exercise test until volitional fatigue, while measuring consumption of oxygen with a computerized metabolic system. Typically measured on a treadmill, VO2 Max has also been found to be accurately and safely measured in stroke survivors on a recumbent stepper, which will be used in this study. A good VO2 Max varies greatly depending on age, and for older participants is typically between 30-40ml/kg/min (higher values indicate greater fitness).	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention.
Change on the 2-minute Step Test	The number of knee raises completed in 2 minutes, raising each knee to a point midway between the patella (kneecap) and iliac crest (top hip bone)	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change on the 30-second chair stands	The number of full stands from a seated position that can be completed in 30 seconds with arms folded across the chest.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change on the Timed Up-and-Go Test	The number of seconds it takes to get up from a seated position, walk 3 m, turn, and return to a seated position.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change on the Functional Reach Test	The number of inches reached forward with each arm with feet flat on the floor at hip width.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change in Gait Speed	The speed in meters per second for the middle 6 m of the 10 m walkway.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes on the Narrative Discourse Sample	Analysis of discourse samples elicited using the WAB-R picture description, the Cat rescue story and the Cinderella story retell, narrative tasks commonly used in aphasia research.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on the Functional Gait Assessment (FGA)	A multi-component assessment of postural stability during walking and ability to perform additional motor tasks while walking.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Change in Center for Epidemiological Studies Depression Scale (CES-D)	The 20-item self-rating questionnaire evaluates perceived mood and level of functioning within the past seven days. The scores range from 0-60. A score equal to or above 16 indicates a person at risk for clinical depression.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on the General Anxiety Disorder scale (GAD-7)	The 7-item self-report scale is used to identify anxiety based on problems experienced in the last two weeks. The scores range from 0-21, with higher scores indicative of more pronounced anxiety symptoms.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on the Pittsburgh Sleep Quality Index (PSQI)	The self-rating scale used to measure the quality and patterns of sleep. It differentiates "poor" from "good" sleep by measuring seven areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction over the last month. The overall score ranges from 0-21, with higher scores indicative of more acute sleep disturbances.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on the Stroke and Aphasia Quality of Life Scale - 39 (SAQOL-39)	This questionnaire is specifically designed to assess quality of life in individuals with stroke and aphasia. The overall quality of life score can range from 1 to 5, with higher values indicating better quality of life and overall well-being.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention; (T4) Follow-up: 3 months after the conclusion of the intervention.
Changes on the Fugl-Meyer Assessment, Upper Extremity portion (FMA-UE)	This is a commonly used outcome measure for assessment of sensorimotor recovery after stroke. We will only use the upper extremity portion of the assessment to supplement other study measures focusing on gait and balance. The FMA-UE assesses movement, coordination, and reflexes associated with the shoulder, elbow, forearm, wrist, and hand and is meant to capture stages of motor recovery after stroke. The FMA-UE consists of 33 items with each item scored on a 3-point ordinal scale (0, 1, or 2), with 0 generally corresponding to no function, 1 to partial function, and 2 to perfect function. The items are summed to provide a final score, ranging from 0-66 points, with lower scores indicative of more pronounced motor impairments of the upper extremity.	(T1) Baseline: at the start of the study or (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention.
Change on the Modified Rankin Scale (MRS)	This is a commonly used 7-point rating scale for measuring the degree of overall disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. MRS is a single item, global outcomes rating scale for patients post-stroke. The measure is scored based on a structured interview. It is used to categorize level of functional independence with reference to pre-stroke activities rather than on observed performance of a specific task. The scale ranges from 0 to 6, with higher scores indicative of more severe disability, with 6 indicating that the patient is dead.	(T1) Baseline: at the start of the study or (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention.
Changes on the National Institute of Health Stroke Scale (NIHSS)	This is a widely used clinical scale for measuring impairment in various domains (consciousness, motor, sensory, attention, language) after stroke. It uses a numerical scale to determine stroke severity, health care providers record the person's performance in 11 categories, such as sensory and motor ability. Each domain is rated on a scale from 0 to 2 or3/4 for certain domains), with 0 indicating no impairment. The total score can range from 0 to 42 points, with higher scores indicating greater severity.	(T1) Baseline: at the start of the study or (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention.
Change in blood pressure at rest	Both systolic and diastolic blood pressure will be measured at rest with a manual blood pressure monitor.	(T1) Baseline: at the start of the study; (T2) Pre-treatment: 1 week prior to the start of the intervention; (T3) Post-treatment: the week immediately following the intervention.
Change in Stepping Cadence	To evaluate overall daily activity levels in the real world, physical activity and sedentary behavior will be recorded using the activPAL4+ activity monitor (PAL Technologies Ltd., Glasgow, UK). The activPAL is a research-grade device that uses a combination of an accelerometer, inclinometer, and gyroscope to objectively measure time spent in different postures, including lying, sitting, standing, and stepping, as well as the intensity and duration of physical activity. We will track the following outcomes to evaluate changes in stepping cadence: steps per day, steps per minute (cadence), and peak 30-minute cadence.	Two one-week periods: one week prior to and one week following the intervention.
Change in Activity Levels	To evaluate overall daily activity levels in the real world, physical activity and sedentary behavior will be recorded using the activPAL4+ activity monitor (PAL Technologies Ltd., Glasgow, UK). The activPAL is a research-grade device that uses a combination of an accelerometer, inclinometer, and gyroscope to objectively measure time spent in different postures, including lying, sitting, standing, and stepping, as well as the intensity and duration of physical activity. We will track the following outcomes to evaluate changes in activity levels: standing time (in minutes), sitting time (in minutes), lying time (in minutes), number of sit-to-stand transitions, lying bouts greater than 30 minutes, and stepping bouts greater than 5 minutes	Two one-week periods: one week prior to and one week following the intervention.

Collaborators and Investigators

• Sponsor: University of California, Berkeley
• Collaborators: University of California, San Francisco; National Institute on Deafness and Other Communication Disorders (NIDCD); California State University, East Bay; University of San Francisco
• Investigators: Principal Investigator: Maria Ivanova, PhD, University of California, Berkeley

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: stroke; cognition; language; physical exercise; balance; high intensity interval training; aphasia; physical fitness
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurobehavioral Manifestations; Communication Disorders; Language Disorders; Speech Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Communication; Stroke; Aphasia; Aphasia, Broca; Aphasia, Wernicke; Motor Activity; Language
• Other Study ID Numbers: 20243771; R01DC022663 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No