Clinical trial NCT01085903: Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia
Official title: Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spatial Neglect
Dysphagia
Keywords: Spatial Neglect
Dysphagia
Arousal
Modafinil
Stroke
Lead sponsor: University of Arkansas
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2010-03-12
Enrollment: 28
Sex: ALL
Minimum age (years): 19
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: P50 Percent Habituation Score
timeFrame: baseline and after three days of intervention
Secondary outcomes:
measure: PVT Fastest 10 Percent of Reaction Times
timeFrame: baseline and after three days of intervention
measure: Power Function Exponent for Oral Bolus Estimation
timeFrame: baseline and after three days of intervention
measure: Time to Swallow Puree Food
timeFrame: baseline and after three days of intervention
Other outcomes:
Locations:
city: Conway
country: United States
facility: Conway Regional Rehabilitation Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Mark S Mennemeier, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Central Arkansas
name: Gary McCullough, PhD
role: PRINCIPAL_INVESTIGATOR
References: