Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Phase 2

Completed

Conditions: Spatial Neglect
Dysphagia

Interventions: Drug: Modafinil
Behavioral: Baseline
Behavioral: CPS
Drug: Placebo
Behavioral: Post CPS
Behavioral: Follow up

Registration Number: NCT01085903

Lead Sponsor: University of Arkansas

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
normal subjects	CPS	Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
stroke subjects	Follow up	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.
stroke subjects	Modafinil	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.
stroke subjects	Placebo	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.
stroke subjects	CPS	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.
stroke subjects	Post CPS	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.
normal subjects	Baseline	Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
normal subjects	Post CPS	Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
normal subjects	Follow up	Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
stroke subjects	Baseline	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.

Primary Outcome Measures

Name	Time	Method
P50 Percent Habituation Score	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).

Secondary Outcome Measures

Name	Time	Method
Power Function Exponent for Oral Bolus Estimation	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	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).
PVT Fastest 10 Percent of Reaction Times	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).

Trial Locations

Locations (2): University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Conway Regional Rehabilitation Hospital
🇺🇸
Conway, Arkansas, United States