Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Dysphagia Clinical Trial

Official title:

Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01085903
• Other study ID #: 110644
• Secondary ID: R21HD055677
• Status: Completed
• Phase: Phase 2
• First received: March 9, 2010
• Last updated: October 17, 2016
• Start date: March 2010
• Est. completion date: August 2015

Study information

• Verified date: October 2016
• Source: University of Arkansas
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 85 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Deglutition Disorders
• Dysphagia
• Spatial Neglect

Intervention

Drug:
• Modafinil
200 mg once daily with morning meal for three days administered only to stroke patients
• 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

Behavioral:
• Baseline
Observations made at baseline before any intervention
• CPS
Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
• Post CPS
20 minutes following the CPS condition.
• Follow up
Follow up testing occurred at 3 months

Locations

Country	Name	City	State
United States	Conway Regional Rehabilitation Hospital	Conway	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Arkansas	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P50 Percent Habituation Score	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).	baseline and after three days of intervention	No
Secondary	PVT Fastest 10 Percent of Reaction Times	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).	baseline and after three days of intervention	No
Secondary	Power Function Exponent for Oral Bolus Estimation	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).	baseline and after three days of intervention	No
Secondary	Time to Swallow Puree Food	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).	baseline and after three days of intervention	No