Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

NCT ID: NCT01085903

Last Updated: 2016-10-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2015-08-31

Brief Summary

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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

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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.

Conditions

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Spatial Neglect Dysphagia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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normal subjects

Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.

Group Type ACTIVE_COMPARATOR

Baseline

Intervention Type BEHAVIORAL

Observations made at baseline before any intervention

CPS

Intervention Type BEHAVIORAL

Submerging each participant's foot into ice water (36-44 F) for 50 seconds.

Post CPS

Intervention Type BEHAVIORAL

20 minutes following the CPS condition.

Follow up

Intervention Type BEHAVIORAL

Follow up testing occurred at 3 months

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.

Group Type ACTIVE_COMPARATOR

Modafinil

Intervention Type DRUG

200 mg once daily with morning meal for three days administered only to stroke patients

Placebo

Intervention Type DRUG

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

Baseline

Intervention Type BEHAVIORAL

Observations made at baseline before any intervention

CPS

Intervention Type BEHAVIORAL

Submerging each participant's foot into ice water (36-44 F) for 50 seconds.

Post CPS

Intervention Type BEHAVIORAL

20 minutes following the CPS condition.

Follow up

Intervention Type BEHAVIORAL

Follow up testing occurred at 3 months

Interventions

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Modafinil

200 mg once daily with morning meal for three days administered only to stroke patients

Intervention Type 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

Intervention Type DRUG

Baseline

Observations made at baseline before any intervention

Intervention Type BEHAVIORAL

CPS

Submerging each participant's foot into ice water (36-44 F) for 50 seconds.

Intervention Type BEHAVIORAL

Post CPS

20 minutes following the CPS condition.

Intervention Type BEHAVIORAL

Follow up

Follow up testing occurred at 3 months

Intervention Type BEHAVIORAL

Other Intervention Names

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Provigil inert baseline observation cold pressor stimulation post cold pressor stimulation three month follow up

Eligibility Criteria

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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
* 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
Minimum Eligible Age

19 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Arkansas

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark S Mennemeier, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Gary McCullough, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Central Arkansas

Locations

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Conway Regional Rehabilitation Hospital

Conway, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Countries

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United States

Other Identifiers

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R21HD055677

Identifier Type: NIH

Identifier Source: secondary_id

View Link

110644

Identifier Type: -

Identifier Source: org_study_id

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