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Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Primary Purpose

Spatial Neglect, Dysphagia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Modafinil
Placebo
Baseline
CPS
Post CPS
Follow up
Sponsored by
University of Arkansas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spatial Neglect focused on measuring Spatial Neglect, Dysphagia, Arousal, Modafinil, Stroke

Eligibility Criteria

19 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Conway Regional Rehabilitation Hospital
  • University of Arkansas for Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

normal subjects

stroke subjects

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
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).
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).

Full Information

First Posted
March 9, 2010
Last Updated
October 17, 2016
Sponsor
University of Arkansas
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT01085903
Brief Title
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

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spatial Neglect, Dysphagia
Keywords
Spatial Neglect, Dysphagia, Arousal, Modafinil, Stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
normal subjects
Arm Type
Active Comparator
Arm Description
Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
Arm Title
stroke subjects
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Modafinil
Other Intervention Name(s)
Provigil
Intervention Description
200 mg once daily with morning meal for three days administered only to stroke patients
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
inert
Intervention Description
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
Behavioral
Intervention Name(s)
Baseline
Other Intervention Name(s)
baseline observation
Intervention Description
Observations made at baseline before any intervention
Intervention Type
Behavioral
Intervention Name(s)
CPS
Other Intervention Name(s)
cold pressor stimulation
Intervention Description
Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
Intervention Type
Behavioral
Intervention Name(s)
Post CPS
Other Intervention Name(s)
post cold pressor stimulation
Intervention Description
20 minutes following the CPS condition.
Intervention Type
Behavioral
Intervention Name(s)
Follow up
Other Intervention Name(s)
three month follow up
Intervention Description
Follow up testing occurred at 3 months
Primary Outcome Measure Information:
Title
P50 Percent Habituation Score
Description
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).
Time Frame
baseline and after three days of intervention
Secondary Outcome Measure Information:
Title
PVT Fastest 10 Percent of Reaction Times
Description
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).
Time Frame
baseline and after three days of intervention
Title
Power Function Exponent for Oral Bolus Estimation
Description
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 Frame
baseline and after three days of intervention
Title
Time to Swallow Puree Food
Description
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).
Time Frame
baseline and after three days of intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark S Mennemeier, PhD
Organizational Affiliation
University of Arkansas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gary McCullough, PhD
Organizational Affiliation
University of Central Arkansas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Conway Regional Rehabilitation Hospital
City
Conway
State/Province
Arkansas
ZIP/Postal Code
72035
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States

12. IPD Sharing Statement

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Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

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