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Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

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: NCT01085903
Recruitment Status : Completed
First Posted : March 12, 2010
Results First Posted : October 18, 2016
Last Update Posted : October 18, 2016
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Arkansas

Tracking Information
First Submitted Date  ICMJE March 9, 2010
First Posted Date  ICMJE March 12, 2010
Results First Submitted Date  ICMJE July 25, 2016
Results First Posted Date  ICMJE October 18, 2016
Last Update Posted Date October 18, 2016
Study Start Date  ICMJE March 2010
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
P50 Percent Habituation Score [ Time Frame: baseline and after three days of intervention ]
This is an electrophysiological measure of arousal - a percent change in the P50 evoked response potential amplitudes with a 250 ms inter stimulus interval. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2010)
  • Predicting response to modafinil among subjects with neglect [ Time Frame: 1 month ]
    We will measure electrophysiological and behavioral indicators of arousal, magnitude estimation in stroke stubjects with and without neglect behavior and in normal control subjects at baseline, immediately following and 20 minutes after cold pressor stimulation. We will then determine in stroke subjects if a response to cold pressor stimulation predicts a response to modafinil (Provigil) and whether either manipulation predicts longer-term improvement (100+/-10 days).
  • Predicting response to modafinil among subjects with dysphagia [ Time Frame: 1 month ]
    We will measure arousal, magnitude estimation for pharyngeal stimulation and swallowing before and after cold pressor stimulation in groups of stroke subjects with and without dysphagia and neglect and in normal control subjects. We will then determine in stroke subjects if a response to cold pressor stimulation predicts a response to modafinil (Provigil) and whether either manipualtion predicts longer-term improvement (100 +/-10 days).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
  • PVT Fastest 10 Percent of Reaction Times [ Time Frame: baseline and after three days of intervention ]
    This is a behavioral measure of arousal - the fastest 10 percent of all cued reaction time trials. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).
  • Power Function Exponent for Oral Bolus Estimation [ Time Frame: baseline and after three days of intervention ]
    This is a behavioral measure of sensation in the oral cavity. The power function exponent is equal to the slope of a regression equation relating bolus size to a person's estimate of that size. An exponent below one implies an underestimate of bolus size. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).
  • Time to Swallow Puree Food [ Time Frame: baseline and after three days of intervention ]
    This is a behavioral measure of swallowing - the time it takes for pureed food to transition across a part of the throat. The difference score is calculated as CPS - placebo and as modafinil - placebo (for stroke subjects only).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia
Official Title  ICMJE Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia
Brief Summary The purpose of this study is to examine how stroke can alter arousal, alertness, neglect and dysphagia, and whether a medication, modafinil, can improve arousal.
Detailed Description

Neglect and dysphagia are two of the most problematic behavioral disorders encountered in stroke rehabilitation with 300,000 patients affected annually in the US. Both disorders impede progress in therapy and both lead to costly medical complications, like falls which are associated with neglect and aspiration pneumonia and malnutrition which are associated with dysphagia. No widely accepted pharmacological treatment exists for either disorder.

A new direction of this application is to view neglect and dysphagia as different disorders that share a common deficit in magnitude estimation (ME). ME refers to one's ability to perceive the intensity of sensory stimulation. Deficits in ME explain how much of a stimulus is neglected by stroke patients. Sensory deficits are also known to produce dysphagia. Perceptual deficits influence how patients response to stimuli like failing to act on all stimuli present (neglect) and failing to generate swallowing reflexes sufficient for normal bolus flow (dysphagia).

We know from previous work that ME is altered by change in cortical arousal following stroke (decreased or hypoarousal). Hypoarousal is evidenced by objective and subjective post-stroke fatigue and daytime sleepiness which occurs in 50% of stroke patients and can persist chronically. Increasing arousal could potentially reverse the perceptual deficits associated with hypoarousal and improve neglect and dysphagia. This proposal manipulates arousal in two ways. Cold pressor stimulation (CPS), immersing the foot in cold water for 50 seconds, is used to increase arousal and reverse neglect and dysphagia temporarily. A brief, 3-day trial of modafinil (Provigil) versus placebo is then used in stroke patients to learn if a positive response to cold-pressor stimulation can predicts patients who respond positively to modafinil.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Spatial Neglect
  • Dysphagia
Intervention  ICMJE
  • Drug: Modafinil
    200 mg once daily with morning meal for three days administered only to stroke patients
    Other Name: Provigil
  • Drug: Placebo
    Subjects will receive a placebo designed to look like 200 mg dose of modafinil. The dose will be taken once daily with the morning meal for three days and will only be administered to stroke patients
    Other Name: inert
  • Behavioral: Baseline
    Observations made at baseline before any intervention
    Other Name: baseline observation
  • Behavioral: CPS
    Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
    Other Name: cold pressor stimulation
  • Behavioral: Post CPS
    20 minutes following the CPS condition.
    Other Name: post cold pressor stimulation
  • Behavioral: Follow up
    Follow up testing occurred at 3 months
    Other Name: three month follow up
Study Arms  ICMJE
  • Active Comparator: normal subjects
    Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
    Interventions:
    • Behavioral: Baseline
    • Behavioral: CPS
    • Behavioral: Post CPS
    • Behavioral: Follow up
  • Active Comparator: stroke subjects
    Stroke subjects are persons who have had a stroke affecting the right hemisphere and are subject to neglect or dysphagia who receive modafinil, placebo, baseline, CPS, Post CPS and Follow up interventions.
    Interventions:
    • Drug: Modafinil
    • Drug: Placebo
    • Behavioral: Baseline
    • Behavioral: CPS
    • Behavioral: Post CPS
    • Behavioral: Follow up
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: October 17, 2016)
28
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2010)
124
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent
  • Willingness to complete study procedures
  • Ability to comprehend and sign informed consent
  • Evidence of unilateral, ischemic stroke based on:

    • Neuroimaging (clinically obtained imaging studies showing evidence of stroke)

      • Acceptable categories of stroke include:
      • Unilateral ischemic stroke
      • Atherothrombotic stroke
      • Cardioembolic stroke
      • Lacunar stroke >1.5 cm
      • Chronic stable, unilateral hemorrhagic stroke
  • Or Behavioral evidence of stroke including:

    • Hemiplegia
    • Unilateral sensory impairment
    • Localized higher cortical dysfunction (e.g. neglect,dysphagia, apraxia)

Exclusion Criteria:

  • Cardiac valvular disease
  • Left heart hypertrophy
  • Poorly controlled hypertension
  • Active variant angina
  • Pre-menopausal women capable of having children, including those using active contraception (precaution for study medication and not applicable to normal subjects)
  • Severe renal or hepatic disease
  • History of psychosis or substance abuse
  • Patients on other Central Nervous System (CNS) stimulants, dopamine agonists or antagonists (antipsychotics)
  • Severe speech comprehension deficit and/or inability to communicate responses
  • Allergies that could put the research subject at risk during the course of the study
  • Cannot speak English
  • Active cerebral neurologic disease other than stroke such as multiple sclerosis or Alzheimer's Disease
  • Active psychiatric illness except past history of treated depression or anxiety disorders
  • For persons needing an MRI - standard MRI exclusion criteria (cardiac pacemaker or defibrillator, artificial heart valves, metallic aneurysm clips eye or ear implants, implanted insulin or infusion pumps, battery activated stimulators, and history of claustrophobia)
  • Concomitant medications excluded: Based on recommendations of manufacturer, the following concomitant medications are excluded: Tricyclic antidepressants and Monoamine oxidase (MAO) inhibitors. Any other CNS stimulation producing medications. Antifungal agents Itraconazole or Ketoconazole as plasma concentrations of modafinil may be increased.
  • Stroke patients will be excluded from the modafinil trial if they cannot swallow a capsule.
  • Stroke patients are excluded if they are able to become pregnant
  • Any other criteria that the PI or study physicians feel would put the volunteer's health at risk during the course of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
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 NCT01085903
Other Study ID Numbers  ICMJE 110644
R21HD055677 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Arkansas
Study Sponsor  ICMJE University of Arkansas
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Mark S Mennemeier, PhD University of Arkansas
Principal Investigator: Gary McCullough, PhD University of Central Arkansas
PRS Account University of Arkansas
Verification Date October 2016

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