Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

This study is currently recruiting participants.
Verified November 2013 by University of Arkansas
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01085903
First received: March 9, 2010
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Neglect
Dysphagia
Drug: Modafinil
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Predicting response to modafinil among subjects with neglect [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    We will measure electrophysiological and behavioral indicators of arousal, magnitude estimation in stroke stubjects with and without neglect behavior and in normal control subjects at baseline, immediately following and 20 minutes after cold pressor stimulation. We will then determine in stroke subjects if a response to cold pressor stimulation predicts a response to modafinil (Provigil) and whether either manipulation predicts longer-term improvement (100+/-10 days).

  • Predicting response to modafinil among subjects with dysphagia [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    We will measure arousal, magnitude estimation for pharyngeal stimulation and swallowing before and after cold pressor stimulation in groups of stroke subjects with and without dysphagia and neglect and in normal control subjects. We will then determine in stroke subjects if a response to cold pressor stimulation predicts a response to modafinil (Provigil) and whether either manipualtion predicts longer-term improvement (100 +/-10 days).


Estimated Enrollment: 124
Study Start Date: March 2010
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: modafinil
Stroke subjects will receive a brief 3-day trial of modafinil and repeat experimental measures.
Drug: Modafinil
200 mg once daily with morning meal for three days
Placebo Comparator: placebo
Stroke subjects will receive a brief 3-day trial of placebo and repeat experimental measures.
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.

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, 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.

  Eligibility

Ages Eligible for Study:   19 Years to 85 Years
Genders Eligible for Study:   Both
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01085903

Contacts
Contact: Mark S Mennemeier, PhD (501) 526-7773 msmennemeier@uams.edu

Locations
United States, Arkansas
Conway Regional Rehabilitation Hospital Recruiting
Conway, Arkansas, United States, 72035
Contact: Gary McCullough, PhD    501-428-1234    gmccullough@uca.edu   
Principal Investigator: Gary McCullough, PhD         
Sub-Investigator: Keith Schluterman, MD         
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Mark S Mennemeier, PhD    501-526-7773    msmennemeier@uams.edu   
Principal Investigator: Mark S Mennemeier, PhD         
Sub-Investigator: Thomas Kiser, MD         
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Mark S Mennemeier, PhD University of Arkansas
Principal Investigator: Gary McCullough, PhD University of Central Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01085903     History of Changes
Other Study ID Numbers: 110644, R21HD055677
Study First Received: March 9, 2010
Last Updated: November 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arkansas:
Neglect
Dysphagia
Arousal
Modafinil
Stroke

Additional relevant MeSH terms:
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Pharyngeal Diseases
Otorhinolaryngologic Diseases
Modafinil
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on April 20, 2014