Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

• 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: University of Arkansas
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): University of Arkansas

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Spatial Neglect; Dysphagia	Drug: Modafinil; Drug: Placebo; Behavioral: Baseline; Behavioral: CPS; Behavioral: Post CPS; Behavioral: Follow up	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia
• Study Start Date: March 2010
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. 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).
2. 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).
3. 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).

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: 110644; R21HD055677 ( U.S. NIH Grant/Contract )
• First Posted: March 12, 2010
• Results First Posted: October 18, 2016
• Last Update Posted: October 18, 2016
• Last Verified: October 2016

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; Vasoconstrictor Agents; Modafinil; Central Nervous System Stimulants; Physiological Effects of Drugs; Wakefulness-Promoting Agents; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action