DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Mechanisms of Neuromuscular Fatigue Post Stroke

Information source: Medical College of Wisconsin
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Stroke

Intervention: duloxetine (Drug); Cyproheptadine (Drug); Placebo (Drug)

Phase: Phase 0

Status: Active, not recruiting

Sponsored by: Medical College of Wisconsin


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.

Clinical Details

Official title: Mechanisms of Neuromuscular Fatigue Post Stroke

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

Primary outcome: Force generation

Secondary outcome: Surface electromyography (EMG)of lower leg muscles.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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.

Locations and Contacts

Medical College of Wisconsin, Milwaukee, Wisconsin 53201, United States
Additional Information

Starting date: August 2011
Last updated: April 8, 2015

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017