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Mechanisms of Neuromuscular Fatigue Post Stroke

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01688570
Recruitment Status : Completed
First Posted : September 20, 2012
Last Update Posted : November 5, 2015
Sponsor:
Information provided by (Responsible Party):
Phillip Nelson, MD, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE September 12, 2012
First Posted Date  ICMJE September 20, 2012
Last Update Posted Date November 5, 2015
Study Start Date  ICMJE August 2011
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2012)
Force generation [ Time Frame: At time of each of 4 testing sessions (all sessions within a 2 year period). ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2012)
Surface electromyography (EMG)of lower leg muscles. [ Time Frame: EMG measurements will be made during each of the four sessions. ]
Sessions will occur at least a week apart and within a 2 year time span.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanisms of Neuromuscular Fatigue Post Stroke
Official Title  ICMJE Mechanisms of Neuromuscular Fatigue Post Stroke
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Stroke
Intervention  ICMJE
  • 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.
    Other Name: Cymbalta
  • Drug: 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.
  • Drug: Placebo
    Single dose, orally, 6 hours prior to the start of the respective testing session. Subjects take a single dose once.
Study Arms  ICMJE
  • Active Comparator: Duloxetine
    Neuromuscular fatigue testing with duloxetine dose
    Intervention: Drug: duloxetine
  • Active Comparator: Cyproheptadine
    Neuromuscular fatigue testing with cyproheptadine dose
    Intervention: Drug: Cyproheptadine
  • Placebo Comparator: Placebo
    Neuromuscular fatigue testing with placebo dose
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 4, 2015)
27
Original Estimated Enrollment  ICMJE
 (submitted: September 16, 2012)
26
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01688570
Other Study ID Numbers  ICMJE UL1RR031973-02( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Phillip Nelson, MD, Medical College of Wisconsin
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Medical College of Wisconsin
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Philip A. Nelson, MD Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP