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Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01085903
First received: March 9, 2010
Last updated: October 17, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Spatial Neglect
Dysphagia
Drug: Modafinil
Drug: Placebo
Behavioral: Baseline
Behavioral: CPS
Behavioral: Post CPS
Behavioral: Follow up
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • P50 Percent Habituation Score [ Time Frame: baseline and after three days of intervention ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • PVT Fastest 10 Percent of Reaction Times [ Time Frame: baseline and after three days of intervention ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 28
Study Start Date: March 2010
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: normal subjects
Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
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
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.
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

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.

  Eligibility

Ages Eligible for Study:   19 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085903

Locations
United States, Arkansas
Conway Regional Rehabilitation Hospital
Conway, Arkansas, United States, 72035
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Mark S Mennemeier, PhD University of Arkansas
Principal Investigator: Gary McCullough, PhD University of Central Arkansas
  More Information

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01085903     History of Changes
Other Study ID Numbers: 110644  R21HD055677 
Study First Received: March 9, 2010
Results First Received: July 25, 2016
Last Updated: October 17, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arkansas:
Spatial Neglect
Dysphagia
Arousal
Modafinil
Stroke

Additional relevant MeSH terms:
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Pharyngeal Diseases
Otorhinolaryngologic Diseases
Modafinil
Armodafinil
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016