Spatial Inattention Grasping Therapy (SIGHT) for rehabilitation of spatial neglect post-stroke: a randomised-controlled multicentre efficacy trial with embedded mechanistic study of determinants of therapy response

Research question: Is SIGHT more efficacious than usual care in reducing spatial neglect in stroke, and what determines therapy response?

Background: The James Lind Alliance and NHS England have prioritised research into effective stroke therapies for cognition. This efficacy trial is directed at spatial neglect or inattention, one of the most disabling and ‘hidden’ cognitive syndromes post-stroke, broadly defined as an inability to attend to the side most affected by the stroke with varying sub-types.

SIGHT is a simple therapy with established proof-of-concept that involves balancing rods with the less affected hand. Due to neglect the rods tilt in the first attempts, but feeling and seeing the rod tilt improves performance which in turn increases attention. Our hypothesis is that SIGHT improves neglect via involvement of a key brain region for grasping, the intraparietal sulcus (IPS).

Aims: (1) determine whether SIGHT, in addition to treatment as usual (TAU), produces greater reduction in neglect than TAU alone; (2) determine whether benefits from SIGHT are still evident 12-weeks post-intervention; (3) determine if therapy response is modified by baseline grasping ability, lesion location, IPS structure and function, stroke severity, visual and/or cognitive deficits.

Methods: multi-centre, assessor-blind, efficacy RCT in ideal controlled conditions. Participants will undergo baseline (T0) measures and then be randomised to one of two groups. Stratification factors are age, neglect severity and IPS preservation.

The intervention phase consists of 7 sessions over a 10-day period. Both groups will receive usual care (TAU). The experimental group will also receive SIGHT 30min/day.

Efficacy measures will be repeated after the intervention phase (T1, primary timepoint) and 12 weeks thereafter (T2). Mechanistic measures will be taken at T0 only. Participants will be adults with neglect 1-week to 60 days post-stroke, able to follow a one-step command and sit for 30min, and not discharged home within next 7 days.

The primary outcome is neglect. Secondary outcomes include neglect sub-types and daily life impact. The sample size of 206 (103 per group, inc. 20% attrition) will allow detection of a significant between-group difference of the primary outcome measure at T1 assuming power of 90% at 5% significance.

For the mechanistic study, a sample of 40 per group (inc. 20% attrition) will provide 90% power to detect a correlation between IPS structure and function and treatment response. Participants will be analysed in their allocated group regardless of compliance (intention-to-treat). A linear multi-level model will be estimated from the data.

The fixed effect will be the baseline values and stratification factors and random effect will be participant.

Timeline: 6 months for trial start-up, 22 months for recruitment, 4 months for T1 and T2 measures, 6 months for statistical analysis, closedown, and dissemination. Total of 38 months.

Impact and dissemination: findings will be pulled into the Cochrane review, later into clinical guidelines and inform a Phase III effectiveness pragmatic trial. The mechanistic study adds significantly to our understanding of neglect recovery and of the profiles of patients that benefit most from rehabilitation. We will register the trial prior to recruitment, publish protocol, efficacy, and mechanistic results, and disseminate the work via trial website, the Stroke Association, scientific and public events.