Mechanisms of Neuromuscular Fatigue Post Stroke

Stroke Clinical Trial

Official title:

Mechanisms of Neuromuscular Fatigue Post Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01688570
• Other study ID #: UL1RR031973-02
• Status: Completed
• Phase: Phase 0
• First received: September 12, 2012
• Last updated: November 4, 2015
• Start date: August 2011
• Est. completion date: May 2015

Study information

• Verified date: November 2015
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

While baseline weakness is clearly an important factor that contributes to disability post stroke, neuromuscular fatigue (the acute reduction in force production) of the paretic musculature likely compounds strength deficits and further exacerbates disability. The proposed study aims to improve our understanding of the mechanisms of neuromuscular fatigue in people post stroke in order to optimize strength training. In healthy individuals, both central (neural) and peripheral (muscle) factors are determinants of neuromuscular fatigue, but preliminary data from our laboratory suggests a greater contribution of central components to neuromuscular fatigue in the paretic musculature. Although cortical pathways are clearly disrupted post stroke, it is likely that brainstem pathways, known to have neuromodulatory effects on spinal motor circuitry, are more involved in the sustaining of force in the paretic leg, compared to the non-paretic and control legs. Therefore, the purpose of this proposal is to examine the role of descending neuromodulatory pathways of the brainstem in neuromuscular fatigue post stroke (Aim 1) and to correlate brainstem-related changes in neuromuscular fatigue to walking function (Aim 2). The investigators propose that stroke survivors' decreased capability to sustain force overtime results from the diminished ability of spinal motoneurons to respond to brainstem neuromodulatory inputs (serotonin (5-HT) and norepinephrine (NE)). Aim 1 will quantify stroke-related decreases in motor output sensitivity to a 5-HT and NE reuptake inhibitor (SNRI), serotonin antagonist, or placebo during sub-maximal intermittent fatiguing knee extension contractions. If motoneurons are desensitized to descending monoamines in chronic stroke patients, then they will be less sensitive to the effects of drugs that increase monoamine levels. The investigators predict that in response to the SNRI or serotonin antagonist, the paretic leg will show less change in time to task failure and a smaller reduction in strength as compared to the non-paretic and control legs. For Aim 2, the investigators predict that stroke subjects with the highest walking function will demonstrate the greatest fatigue-related changes in response to the SNRI. This proposal adopts an innovative model of motor impairment post stroke by including the role of subcortical structures in neuromuscular fatigue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

General

• be at least 18 years of age

• Cognitively able to give informed consent Stroke

-= 6 months post diagnosis of unilateral cortical stroke

• residual leg paresis

Exclusion Criteria:

General

• chronic low back or hip pain

• major psychiatric disorders (e.g. depression

• substance abuse

• head trauma

• neurodegenerative disorder

• any uncontrolled medical disorder (e.g. hypertension)

• taking any medication or supplement (e.g. St. John's Wort) that has 5-HT or NE mechanisms of action(including Monoamine oxidase inhibitors (MAO) inhibitors)

• narrow angle glaucoma

• chronic liver or kidney disorders Stroke

• history of multiple strokes

• people who are unable to follow 2 step commands

• people who cannot walk = 10 ft without physical assistance.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• duloxetine
Single dose, orally (pill), 30 mg, taken 6 hours prior to start of the testing session. Subjects will only take a single dose of duloxetine once.
• Cyproheptadine
Single dose, orally, 8 mg, 6 hours prior to the start of the respective testing session. Subjects will take a single dose of cyproheptadine once.
• Placebo
Single dose, orally, 6 hours prior to the start of the respective testing session. Subjects take a single dose once.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Force generation	Sub-maximal and maximal force measurements will be made during brief contractions during each of the four testing sessions. All sessions will occur at least one week apart and within a total time span of 2 years.	At time of each of 4 testing sessions (all sessions within a 2 year period).	No
Secondary	Surface electromyography (EMG)of lower leg muscles.	Sessions will occur at least a week apart and within a 2 year time span.	EMG measurements will be made during each of the four sessions.	No