Combined Optokinetic Stimulation and Cueing-based Reading Therapy to Treat Hemispatial Neglect Following Stroke

Study Overview
=================
Brief Summary
-----------------
Spatial neglect represents a common and severe cognitive disorder following unilateral (mostly right hemisphere) stroke. Patients are unaware of objects, persons and even own body parts in the (usually left) hemispace opposite to their brain lesion. While there is spontaneous remission in some patients, neglect symptoms persist in many stroke survivors which is associated with a poor functional outcome. Although different therapeutic approaches (including cognitive interventions, non-invasive brain stimulation and drugs) have been investigated in the last decades, an established therapy is still missing. Hence, there is a clear need for an effective and feasible intervention that can be applied in rehabilitation centers. This study is dedicated to assess the effect of a cognitive treatment consisting of combined optokinetic stimulation (OKS) and cueing-based reading therapy (READ) on hemispatial neglect and the neglect-related functional disability in right-hemisphere stroke patients. It will be a mono-centric, randomized, controlled, clinical trial. Using a crossover design with two arms, patients will either receive the intervention therapy (OKS-READ) first and subsequently the control treatment (neuropsychological training not targeting visuospatial attention) or they will start in the control arm and then switch to the intervention. Each treatment phase consists of 15 therapy sessions lasting 30 to 45 minutes. The outcome will be assessed at different time points, including established neuropsychological tests for spatial neglect and a clinical score of neglect-related functional disability.

Detailed Description
-----------------
see above

Official Title
-----------------
Randomized Controlled Trial of Combined Optokinetic Stimulation and Cueing-based Reading Therapy to Treat Hemispatial Neglect Following Stroke (OKS-READ Study)

Conditions
-----------------
Spatial Neglect

Intervention / Treatment
-----------------
* Behavioral: Optokinetic stimulation and cueing-based reading therapy (OKS-READ)
* Behavioral: General neuropsychological treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: a first-time stroke in the right hemisphere (confirmed by cranial CT or MRI) within the last six months, a left-sided hemispatial neglect (as detected in at least one subtest of the neuropsychological test battery at screening), the ability to read and understand German language and the ability to give informed consent. Exclusion Criteria: dementia other structural brain lesions besides the unilateral stroke (e.g. multiple or bilateral stroke lesions, hydrocephalus, inflammatory lesions, etc.) low vision (corrected <0.7) due to ophthalmological diseases

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study will be a mono-centric, randomized, controlled, clinical trial. Using a crossover design with two arms, patients will either receive the intervention therapy first and then the control treatment or they will start in the control arm and then switch to the intervention.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention-Control (IC)<br>In the Intervention-Control (IC) arm, patients will first receive the intervention (OKS-READ) containing 15 individual therapy sessions within a maximum time period of 28 days. Afterwards they will receive the control therapy (again 15 sessions within max. 28 days). | Behavioral: Optokinetic stimulation and cueing-based reading therapy (OKS-READ)<br>* Each intervention session starts with an optokinetic stimulation (OKS) of at least 15 minutes duration. A pattern of squares, dots, triangles and stars will coherently and continuously move to the left on a computer screen in front of the patients. Patients are instructed to choose one stimulus and follow it with the eyes until it has reached the left side of the screen, then jump to the right edge of the screen and start again. The second part of each intervention session is the cueing-based reading therapy (READ), which will also last at least 15 minutes. The task of the patient is to read out loud words or a text presented on a paper in front of them. We will use exogenous (e.g., the therapist highlights words when they were omitted) and endogenous cues (verbal instructions which require intrinsic action by the patient) to facilitate attentional shifts to the left. The intensity of cueing will be matched to the actual severity of neglect (adaptive therapy).<br>Behavioral: General neuropsychological treatment<br>* As a control treatment the patients will receive neuropsychological treatment without targeting visuospatial attention. Examples for components implemented are supporting conversations, diagnostic assessments (e.g. memory diagnostics) and training of memory and executive functions.<br>|
| Active Comparator: Control-Intervention (CI)<br>In the Control-Intervention (CI) arm, patients will first receive the control therapy (15 sessions within max. 28 days), followed by the intervention phase (15 therapy sessions OKS-READ within a maximum time period of 28 days). | Behavioral: Optokinetic stimulation and cueing-based reading therapy (OKS-READ)<br>* Each intervention session starts with an optokinetic stimulation (OKS) of at least 15 minutes duration. A pattern of squares, dots, triangles and stars will coherently and continuously move to the left on a computer screen in front of the patients. Patients are instructed to choose one stimulus and follow it with the eyes until it has reached the left side of the screen, then jump to the right edge of the screen and start again. The second part of each intervention session is the cueing-based reading therapy (READ), which will also last at least 15 minutes. The task of the patient is to read out loud words or a text presented on a paper in front of them. We will use exogenous (e.g., the therapist highlights words when they were omitted) and endogenous cues (verbal instructions which require intrinsic action by the patient) to facilitate attentional shifts to the left. The intensity of cueing will be matched to the actual severity of neglect (adaptive therapy).<br>Behavioral: General neuropsychological treatment<br>* As a control treatment the patients will receive neuropsychological treatment without targeting visuospatial attention. Examples for components implemented are supporting conversations, diagnostic assessments (e.g. memory diagnostics) and training of memory and executive functions.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neglect symptom severity (neuropsychological test performance) | Composite score of different established computerized tests assessing spatial neglect (minimum 0%, maximum 100%, higher score means better outcome) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 
| Neglect-related functional disability | Clinical score of neglect-related functional disability (Catherine Bergego Scale, CBS; minimum 0, maximum 30, higher score means worse outcome) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neglect dyslexia | Performance in the Menu reading task of the Behavioural Inattention Test battery (minimum 0 correct words (worst outcome), maximum 24 correct words (best outcome) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 
| Attention bias during a visuo-motor cancellation task | Bias of the Center of Cancellation (CoC) during the Bells test (values between -1 (strongest leftward bias), 0 (no bias) and +1 (strongest rightward bias) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 
| Oculomotor bias during visual exploration | Bias of the Center of Fixation (CoF) during free viewing of naturalistic photographs as measured with an infrared remote eye tracker (values between -1 (strongest leftward bias), 0 (no bias) and +1 (strongest rightward bias) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 
| Anosognosia | Difference between investigator-assessed CBS score and the patient's self-assessed CBS score | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 
| Non-neglect specific functional outcome (Barthel) | Barthel Index (min. 0, max. 100, higher score means better outcome) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) | 
| Functional Independence (FIM) | Functional Independence Measure (18 items scale with scores between 0 and 7 points; higher scores mean better outcome) | Intra-individual difference of the outcome's change during 3 weeks Intervention versus 3 weeks Control phase, i.e. (T3 on Day 21 - T2 on Day 1) - (T5 on Day 42 - T4 on Day 22) |