Locomotor Recovery and Compensation Post-stroke (LRC) (LRC)

The proposed research will characterize of the time course of neurological and locomotor recovery as well as development of compensatory strategies throughout sub-acute and chronic phases post stroke. In addition, we will also investigate the extent to which measures of recovery and compensation are malleable and can be altered with specific interventions in both the early and late stages post-stroke. Delineation of the time course of development and magnitude of patterns of recovery and compensation should result in alternative predictive "rules' regarding how patients early post-stroke could recovery functional and neurological function.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Behavioral: high-intensity training focused on stepping in variable contexts

Detailed Description

Recovery of locomotion is a primary goal of rehabilitation post-stroke and a major determinant of future morbidity and mortality. While substantial recovery is observed early post-stroke, recent evidence suggests the magnitude and time course of recovery is deterministic and based primarily on initial motor deficits. The "proportional recovery" rule suggests ~70% of neurological recovery (measured by the lower limb Fugl-Meyer Assessment - LL-FMA) is typically achieved and is not influenced by the dosage of therapy. These findings suggest the physical interventions applied to patients are of minimal importance to long-term recovery. That hypothesis conflicts directly with our recent efforts suggesting that maximizing the amount and intensity of task-specific (stepping) practice (high-intensity training; HIT) directly influences gains in locomotor function. Providing HIT at heart rates (HRs) greater than traditional aerobic paradigms (mean 110% baseline HRmax) is associated with gains in locomotor speed, which challenges the notion of "proportional recovery".

These conflicting hypotheses likely arise from differences in terminology and methodology used to characterize recovery post-stroke. First, the traditional measure of neurological recovery (LL-FMA) does not adequately characterize other impairments (strength, postural stability) that are more closely associated to locomotor function and are responsive to physical interventions. Second, despite gains in selected impairments, patients often utilize alternative (compensatory) movement patterns to accomplish locomotor tasks. More directly, locomotor recovery (i.e., speed/distance) is often accomplished using strategies employed prior to stroke and compensatory strategies, particularly in those with substantial impairments.

Our central hypothesis is that if changes in neurological recovery are deterministic, other measures of locomotor recovery or compensations may also be predictable. Our published data detail how HIT or conventional interventions can alter impairments and locomotor recovery, as well as changes in locomotor compensations. More directly, our data provide evidence that specific subgroups of patients demonstrate substantial compensations with improved recovery, whereas others reveal limited changes despite similar interventions. Data that detail the progression of neurological recovery, locomotor recovery, and locomotor compensations throughout the subacute to chronic phase post-stroke and their responsiveness to HIT is uncertain. Similar to upper limb recovery algorithms, predictions of mobility outcomes could provide valuable information to clinicians who make decisions regarding patient's prognosis, including whether patients will be able to walk with or without assistance or at certain speeds, and what compensatory strategies they may require to ambulate independently (braces, devices or altered movement patterns). The overarching goal of this project is to examine the time course of neurological and locomotor recovery, and associated compensatory strategies, over the subacute to chronic stages post-stroke and their responsiveness to HIT.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas G Hornby; Phone Number: 3123508291; Email: tghornby@Iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Recruiting
      • Rehabilitation Hospital of Indiana
      • Contact: Thomas G Hornby; Phone Number: 312-350-8291; Email: tghornby@Iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• individuals early post-stroke (<15-30 days)
• first ever stroke
• unilateral hemiparesis
• currently receiving inpatient rehabilitation
• ability to follow 1-step commands
• provision of informed consent
• medical clearance from the rehabilitation physician to participate. \

Exclusion criteria:

• uncontrolled cardiovascular, metabolic or respiratory disease that limits exercise participation (e.g., congestive heart failure, resting blood pressure > 200/110 mmHg, uncontrolled diabetes, end-stage renal disease)
• absolute criteria for termination of exercise testing during initial and repeated ECG testing during graded exercise testing using ACSM guidelines .
• other orthopedic or neurological disorder that limited walking prior to stroke

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Phase 1; Observational evaluations for 6 months followed by 3-4 months of high-intensity training (HIT)	Behavioral: high-intensity training focused on stepping in variable contexts; Approximately 10 weeks (~30 sessions) of high-intensity training; Other Names: HIT
Other: Phase 2; Observational evaluations for 1 month followed by 3-4 months of high-intensity training (HIT)	Behavioral: high-intensity training focused on stepping in variable contexts; Approximately 10 weeks (~30 sessions) of high-intensity training; Other Names: HIT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait speed	Walking speed over 6 m	15 days post-stroke
Gait speed	Walking speed over 6 m	1 month
Gait speed	Walking speed over 6 m	2 months,
Gait speed	Walking speed over 6 m	4 months,
Gait speed	Walking speed over 6 m	6 months,
Gait speed	Walking speed over 6 m	9 months,
Gait speed	Walking speed over 6 m	12 months
Walking distance	Distance covered over 6 min	15 days post-stroke,
Walking distance	Distance covered over 6 min	1 month,
Walking distance	Distance covered over 6 min	2 months,
Walking distance	Distance covered over 6 min	4 months,
Walking distance	Distance covered over 6 min	6 months,
Walking distance	Distance covered over 6 min	9 months,
Walking distance	Distance covered over 6 min	12 months
Gait kinematics	peak hip, knee, ankle range of motion	15 days
Gait kinematics	peak hip, knee, ankle range of motion	1 month
Gait kinematics	peak hip, knee, ankle range of motion	2 months
Gait kinematics	peak hip, knee, ankle range of motion	4 months
Gait kinematics	peak hip, knee, ankle range of motion	6 months
Gait kinematics	peak hip, knee, ankle range of motion	9 months
Gait kinematics	peak hip, knee, ankle range of motion	12 months

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Rehabilitation Hospital of Indiana
• Investigators: Principal Investigator: Thomas G Hornby, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: IU2011618233; 1R01NS118009 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data available upon reasonable request
• IPD Sharing Time Frame: after completion of study for 3 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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