Optimal Non-invasive Brain Stimulation for Peripheral Vision

The Hong Kong Polytechnic University

Status: Enrolling

Conditions: Glaucoma

Treatments: Device: transcranial electrical stimulation (tES)

Study type: Interventional

Funder types: Other

Identifiers

NCT04846140

R5047-19

Details and patient eligibility

About

Glaucoma is a complex disease that can result in progressive vision loss. There are no treatments that restore vision lost to glaucoma. However, recent studies have shown that vision can be improved by non-invasive brain (NIBS) stimulation and visual training. In this study, we aim to compare and find out the optimal non-invasive brain stimulation model (transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS)) for improving peripheral vision in glaucoma patients. The proposed treatment is the application of transcranial electrical stimulation (tES) onto the participant's head, with brain stimulation aimed at the Primary Visual Cortex toward the occipital pole. The investigators hypothesize that the tES will enable higher performance in the reading task and secondary measures due to an increase in the cortical excitability of the stimulated brain cells, and tRNS will generate the greatest acute improvement in peripheral vision than either a-tDCS, tACS, or sham stimulation.

Full description

This study uses a within-subjects, double-blind, placebo-controlled design and will be carried out in Hong Kong (The Hong Kong Polytechnic University).

Participants who will be recruited are 40 glaucoma patients aged 18 to 80, diagnosed with primary open-angle or normal-tension glaucoma with relative scotoma in both eyes. All participants will take part in 4 stimulation sessions (completion of active a-tDCS, tACS, tRNS, and sham stimulation in random order) with at least 48-hour separation between visits to wash out active stimulation effects.

The primary outcome is high-resolution perimetry that will be used to measure the visual field of participants. The secondary outcome is multifocal visual evoked potential (mfVEP) that will be used to measure the electrophysiological changes in the visual cortex.

The study consists of 5 visits:

Visit 1: Eligibility assessment (refer to the inclusion and exclusion criteria).

Visits 2 - 5: Stimulation sessions (completion of active a-tDCS, tACS, tRNS, and sham stimulation in random order) with at least 48-hours separation between visits to wash out active stimulation effects. An established protocol will be used. Briefly, active a-tDCS (2 mA), tACS (2 mA), tRNS (2 mA) or sham a-tDCS will be delivered for 20 minutes. The anodal electrode will be placed at Oz (visual cortex) while the cathodal electrode will be placed on the left cheek to facilitate stimulation of cells corresponding to the para-central retina that are located within the calcarine sulcus. Active stimulation will involve the delivery of 2 mA current continuously, while the fade-in-short-stimulation-fade-out approach will be used for the sham condition, in which the stimulation will be ramped down after 30 seconds of stimulation. Both the participant and experimenter will be masked to the stimulation type.

The average detection accuracy, response time, and functional connectivity will be analyzed using a within-subjects ANOVA with factors of Stimulation type (a-tDCS vs. tACS vs. tRNS vs. sham) and Time (pre and post-stimulation). Significant interactions will be investigated using post-hoc Bonferroni-adjusted paired sample t-tests. A significant interaction between Stimulation type and Time for the primary outcome followed by a significant post-hoc comparison with a p-value <0.05 favoring tRNS would be consistent with our hypothesis.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age range from 18 to 80 years;
2. Diagnosis of primary open angle or normal tension glaucoma with relative scotoma in both eyes;
3. A relative scotoma defined as a Humphrey Field Analyser (HFA) threshold perimetry loss (mean deviation of ≤-6dB) within the central 30° of the visual field for at least one eye;
4. Best-corrected distance visual acuity of 6/12 or better (equivalent to 0.3 logMAR acuity or better to confirm that participant's central vision is preserved);
5. Stable vision and visual field loss for at least 3 months;
6. With a cognitive functional score of 22 or above in the Montreal Cognitive Assessment - Hong Kong version (HK-MoCA) (to confirm participant's intact cognitive function).

Exclusion criteria

1. Ocular diseases other than glaucoma (e.g. age-related macular degeneration, diabetic retinopathy, moderate to severe cataract) or severe hearing impairment (to ensure that participant can hear the instructions clearly during assessments and training);
2. Severe medical problems (e.g. stroke, Parkinson's disease) or self-reported neurological (e.g. brain surgery, brain tumor, peripheral neuropathy), or cognitive disorders (e.g. diagnosed dementia or cognitive impairment);
3. Self-reported vestibular or cerebellar dysfunction, history of vertigo;
4. Using any medications for any neurological conditions or psychiatric drugs (e.g. sedative, hypnotic) that might interfere with motor control;
5. Contraindications for non-invasive brain stimulation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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40 participants in 4 patient groups

tDCS group

Experimental group

Description:

This group is defined as the participants who will receive tDCS at the first session. Participants in this group will receive 4 stimulation types (active a-tDCS, tACS, tRNS, and sham) in random order with at least a 48-hour separation between visits.

Treatment:

Device: transcranial electrical stimulation (tES)

tACS group

Experimental group

Description:

This group is defined as the participants who will receive tACS at the first session. Participants in this group will receive 4 stimulation types (active a-tDCS, tACS, tRNS, and sham) in random order with at least a 48-hour separation between visits.

Treatment:

Device: transcranial electrical stimulation (tES)

tRNS group

Experimental group

Description:

This group is defined as the participants who will receive tRNS at the first session. Participants in this group will receive 4 stimulation types (active a-tDCS, tACS, tRNS, and sham) in random order with at least a 48-hour separation between visits.

Treatment:

Device: transcranial electrical stimulation (tES)

sham group

Experimental group

Description:

This group is defined as the participants who will receive sham stimulation at the first session. Participants in this group will receive 4 stimulation types (active a-tDCS, tACS, tRNS, and sham) in random order with at least a 48-hour separation between visits.

Treatment:

Device: transcranial electrical stimulation (tES)