Identifying and Treating Arousal Related Deficits in Neglect and Dysphagia

Completed

Phase 2 Results

Trial Description

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.

Conditions

Interventions

  • Placebo Drug
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: placebo
    Description: Stroke subjects will receive a brief 3-day trial of placebo and repeat experimental measures.
    ARM 2: Kind: Experimental
    Label: stroke subjects
    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.
  • Modafinil Drug
    Other Names: Provigil
    Intervention Desc: 200 mg once daily with morning meal for three days administered only to stroke patients
    ARM 1: Kind: Experimental
    Label: modafinil
    Description: Stroke subjects will receive a brief 3-day trial of modafinil and repeat experimental measures.
    ARM 2: Kind: Experimental
    Label: stroke subjects
    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.
  • Follow up Other
    Intervention Desc: Follow up testing occurred at 3 months
    ARM 1: Kind: Experimental
    Label: normal subjects
    Description: Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
    ARM 2: Kind: Experimental
    Label: stroke subjects
    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.
  • Baseline Behavioral
    Other Names: baseline observation
    Intervention Desc: Observations made at baseline before any intervention
    ARM 1: Kind: Experimental
    Label: normal subjects
    Description: Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
    ARM 2: Kind: Experimental
    Label: stroke subjects
    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.
  • CPS Behavioral
    Other Names: cold pressor stimulation
    Intervention Desc: Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
    ARM 1: Kind: Experimental
    Label: normal subjects
    Description: Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
    ARM 2: Kind: Experimental
    Label: stroke subjects
    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.
  • Post CPS Behavioral
    Other Names: post cold pressor stimulation
    Intervention Desc: 20 minutes following the CPS condition.
    ARM 1: Kind: Experimental
    Label: normal subjects
    Description: Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
    ARM 2: Kind: Experimental
    Label: stroke subjects
    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.

Trial Design

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

Outcomes

Type Measure Time Frame Safety Issue
Primary Predicting response to modafinil among subjects with neglect 1 month No
Primary Predicting response to modafinil among subjects with dysphagia 1 month No
Primary P50 Percent Habituation Score baseline and after three days of intervention No
Secondary PVT Fastest 10 Percent of Reaction Times baseline and after three days of intervention No
Secondary Power Function Exponent for Oral Bolus Estimation baseline and after three days of intervention No
Secondary Time to Swallow Puree Food baseline and after three days of intervention No

Sponsors