Ischemic Conditioning Improves Walking Function Post Stroke

Stroke Clinical Trial

Official title:

Ischemic Conditioning Improves Walking Function Post Stroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04038697
• Other study ID #: HR-1812027206
• Status: Recruiting
• Phase: N/A
• Start date: December 20, 2018
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Medical College of Wisconsin
• Contact: Matthew J Durand, Ph.D.
• Phone: 4149555619
• Email: mdurand[@]mcw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This innovative study will address scientific and clinical areas relatively unexplored in chronic stroke that could lead to greater recovery of walking. Ischemic Conditioning (IC) is a non-invasive, simple procedure that improves motor function, exercise performance and cardiovascular function in healthy controls, but it has never been applied to the stroke population. We postulate that IC enhances the recruitment of motoneurons and results in positive neural adaptations, improves vascular endothelial function and peripheral blood flow, and together these improvements result in an increased capacity to exercise and faster walking speed. Future studies will examine the effects of IC and traditional therapy at different time points of recovery post stroke, durability of IC, molecular mechanisms of neural and cardiovascular adaptation and the efficacy compared with other adjuncts.

Description:

This study will quantify the effects of Ischemic Conditioning and treadmill training on improvements in: walking speed, leg strength, neuromuscular fatigability and the hyperemic blood flow response to muscle contractions, and vascular endothelial function and aerobic exercise capacity. A randomized control design will be used with three groups of chronic stroke survivors enrolled for four weeks of training (3x/week; 12 sessions total). The groups are: IC + Treadmill Training, IC Sham + Treadmill Training, and IC only. We will also enroll a group of age- and sex-matched healthy control subjects who will undergo IC + Treadmill Training. All Aims will be tested concurrently over a five-year period. All studies will be performed in Cramer Hall at Marquette University in the Integrated Neural Engineering Rehabilitation Laboratories, the Human Performance Assessment Core, and the Physical Therapy Clinic.

Randomization of stroke patients to the three intervention groups will be performed by using randomized block designs (randomly chosen block sizes of 3, 6 and 9). This number accounts for possible dropouts and the use of non- parametric methods.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria (Stroke Survivors):

1. be = 1 year post diagnosis of a unilateral, cortical stroke and have residual lower extremity paresis

2. be between the ages of 18-85

3. be able to give informed consent

4. walk slower than normative values based on age and sex

Exclusion Criteria (Stroke Survivors):

1. history of deep vein thrombosis or any condition in which transient ischemia to the lower extremity is contraindicated

2. inability to follow 2 step commands

3. chronic low back or hip pain

4. history of substance abuse

5. history of head trauma

6. comorbid neurological disorder

7. any uncontrolled medical condition

8. pacemaker

9. any condition where fatiguing contractions or resisted leg contractions are contraindicated

10. inability to walk for 5 minute bouts on a treadmill with a harness supporting up to 50% of the body weight at 80% of over-ground self-selected walking speed.

Inclusion Criteria (Healthy Control Subjects):

1. be between ages of 18-85

2. be able to give informed consent

Exclusion Criteria (Healthy Control Subjects):

1. Those listed above for stroke survivors

2. History of Stroke

Related Conditions & MeSH terms

• Hemorrhagic Stroke
• Ischemia
• Ischemic Stroke
• Myocardial Infarction
• Stroke
• Stroke Hemorrhagic
• Stroke, Cardiovascular
• Stroke, Ischemic

Intervention

Procedure:
• Ischemic Conditioning
Ischemic conditioning is a well-defined, non-invasive procedure which consists of inflating a blood pressure cuff around a limb (in our study, the paretic leg), inflating the cuff to 225 mmHg to occlude blood flow to the limb for 5 minutes, releasing the cuff for 5 minutes, and repeating 5 times. In our study, participants assigned to the IC Only and IC + Treadmill Training groups will undergo twelve sessions of ischemic conditioning over a four-week period.
• Ischemic Conditioning Sham
Ischemic conditioning sham consists of the same setup as ischemic conditioning, which consists of inflating a blood pressure cuff around a limb (in our study, the paretic leg), inflating the cuff to 10 mmHg for 5 minutes, releasing the cuff for 5 minutes, and repeating 5 times. 10 mmHg is a sufficient inflation pressure for study participants to perceive some cuff tightness, but is not high enough to occlude blood flow. In our study, participants assigned to the IC Sham + Treadmill Training groups will undergo twelve sessions of ischemic conditioning sham over a four-week period.
• Treadmill Training
Participants will perform 3 treadmill training sessions/week for a 4 week period (12 sessions total). Treadmill training will immediately follow IC or IC Sham. Personnel performing the treadmill training will be blinded to the IC treatment group. Subjects will walk on a treadmill for six, 5-minute intervals. Walking speed will be continuously adjusted to maintain heart rate between 50% and 60% of age-adjusted heart rate reserve to minimize the confounder of intensity. If individuals cannot walk at 80% of their overground self-selected walking speed, for 5 minutes, they will be assisted into a body weight support harness. Body weight support will be adjusted (up to 50%) such that individuals can walk at 80% of their over ground walking speed for five minutes and adjusted accordingly throughout the session. Participants assigned to the Treadmill + IC and Treadmill + IC Sham groups will receive Treadmill Training.

Locations

Country	Name	City	State
United States	Marquette University	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Medical College of Wisconsin	Marquette University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Six minute walk test	Clinical test for walking endurance	Change from baseline to 4 weeks.
Other	Lower Extremity Fugl Meyer	Clinical test for coordination	Change from baseline to 4 weeks.
Other	Manual Muscle Test	Clinical test for strength	Change from baseline to 4 weeks.
Other	Modified Ashworth Scale	Clinical test for spasticity.; The Modified Ashworth scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Higher scores indicate worse spasticity. The scores and scale are as follows: 0: No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of motion.; More marked increase in muscle tone through most of the range of motion, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	Change from baseline to 4 weeks.
Other	Bipolar Surface Electromyography (EMG) Measurements	Bipolar surface EMG of bilateral lower extremities will be measured during walking using electrodes placed on the following muscles: rectus femoris, vastus medialis, medial hamstrings, tibialis anterior, and medial gastrocnemius.	Change from baseline to 4 weeks.
Other	Voluntary Activation of Paretic Muscle	Voluntary activation (neural drive to the muscle) will be assessed by stimulating the motor nerve with a brief stimulus (superimposed twitch) while the subject performs a maximal voluntary contraction (MVC).	Change from baseline to 4 weeks.
Other	Surface EMG Motor Unit Measurements	Surface motor unit potentials will be recorded from the vastus lateralis (VL) muscle during muscle contractions using a multi-channel linear array of 64 EMG electrodes	Change from baseline to 4 weeks.
Other	Hyperemic Blood Flow in Response to Muscle Contractions	Blood flow through the superficial femoral artery will be measured before and immediately after knee extensor muscle contractions using Doppler ultrasound.	Change from baseline to 4 weeks.
Other	Heart Rate Variability (HRV)	We will use HRV analysis to determine the effects of IC and treadmill training on sympathetic and parasympathetic control of heart rate at the same time points as above.	Change from baseline to 4 weeks.
Other	Step Cadence	The number of steps per minute when walking at self-selected walking speed will be measured.	Change from baseline to 4 weeks.
Other	Step Length	The average step length during self-selected walking speed will be measured.	Change from baseline to 4 weeks.
Other	Step Velocity	Step velocity, the product of cadence and step length, expressed in units of distance per time, will be measured during self-selected walking speed.	Change from baseline to 4 weeks.
Other	Ground Reaction Force	Ground reaction force (N) will be measured during the different phases of gait during the 10 meter walk test and reported separately.	Change from baseline to 4 weeks.
Other	Ankle, Hip and Knee Joint Trajectories	Ankle, hip and knee joint trajectories (Angle) will be measured separately, in both legs, during the different phases of gait during the 10 meter walk test and reported as separate values.	Change from baseline to 4 weeks.
Primary	Self Selected Walking Speed	We will measure how fast participants walk during the 10 meter walk test.	Change from baseline to 4 weeks.
Secondary	Knee Extensor Leg Strength	Pre-treatment and after 1, 6, and 12 sessions of ischemic conditioning. We will also test 1 month post intervention	Change from baseline to 4 weeks.
Secondary	Knee Extensor Fatigability	Pre-treatment and after 1, 6, and 12 sessions of ischemic conditioning. We will also test 1 month post intervention	Change from baseline to 4 weeks.
Secondary	Flow Mediated Dilation of Non-Paretic Brachial Artery and Paretic Popliteal Artery	Pre-treatment and after 1, 6, and 12 sessions of ischemic conditioning. We will also test 1 month post intervention	Change from baseline to 4 weeks.
Secondary	Peak Oxygen Consumption	Using a recumbent bicycle and metabolic cart, we will test whole body oxygen consumption during a graded exercise test	Change from baseline to 4 weeks.