Trial of a non-invasive stimulation method to treat visual hallucinations in people with macular degeneration

Plain English summary of protocol

Background and study aims
Charles Bonnet Syndrome (CBS) occurs in patients who experience recurrent visual hallucinations (VH) secondary to visual impairment, such as macular degeneration, and in the absence of psychiatric illness. It is estimated that up to fifty percent of patients with macular degeneration experience visual hallucinations and up to one-third of those consider the experience to be distressing and disruptive to day-to-day life. Currently, there are no effective treatments for CBS. Drug treatments can include medications known as cholinesterase inhibitors, anticonvulsants and antipsychotics, which have been found to offer little benefit and often have severe side effects. Therefore, there is a distinct need to develop new and effective treatments. Earlier research has suggested that visual hallucinations experienced by people with eye disease are the result of increased activity (or excitability) in the visual cortex, the seeing part of the brain. It is believed that as the visual cortex is deprived of sensory information sent from the eyes due to visual impairment, this causes spontaneous and independent activity to occur in the visual system, resulting in the formation of visual hallucinations. Transcranial direct current stimulation (tDCS) is an established, non-invasive (i.e. applied from outside the body) and well-tolerated technique which can alter the activity or excitability levels of the brain using a weak electrical current. This change in the brain has also been found to be sustained, particularly when repeated tDCS is applied. tDCS involves the attachment of two electrode pads to the scalp which produce a negative pole (anode) which increases activity in the brain, and a positive pole (cathode) which diminishes activity. As CBS is understood to be the result of increased excitability of the visual cortex, the aim of this study is to test whether applying cathodal stimulation to this area will result in a reduction in this activity and reduce visual hallucinations, thus providing direct evidence that increased excitation or activity in the visual system is responsible for visual hallucinations in CBS.

Who can participate?
Patients aged over with 18 Charles Bonnet Syndrome

What does the study involve?
The study involves two phases. In the first phase, CBS patients who experience continuous or highly frequent visual hallucinations (multiple hallucinations each day) receive active cathodal tDCS over the visual cortex. Before stimulation, electroencephalography (EEG), a technique which measures brain activity, is used to indicate which areas of the visual cortex are demonstrating increased excitability and are the best target for cathodal stimulation. In order to determine the best stimulation settings needed to cause an effective reduction in visual hallucinations, the researchers alter the current strengths, electrode positions, and lengths of stimulation. Participants then provide immediate feedback as to whether stimulation has caused an alteration in their visual hallucinations. In Phase II, a second group of CBS patients are randomly allocated to receive a course of active tDCS (using the optimal settings found during phase I) and a course of placebo (dummy) tDCS over several days. Following a four week period, participants return and receive the opposite treatment (i.e. if they received placebo tDCS in their first week, they receive active tDCS in their second). Before stimulation, patients undergo assessments of their visual hallucination severity, which are then followed up immediately after treatment ends to see if stimulation has produced any benefits. In addition, further techniques are used to look at activity levels in the brain before and after stimulation and the effect of stimulation on vision. These include transcranial magnetic stimulation (TMS), a technique which activates the visual part of the brain using a special magnetic device against the back of the head, magnetic resonance imaging (MRI), which collects detailed images of the brain using a magnetic resonance scanner, and EEG to measure brain signals as in Phase I. Patients also have their eyesight assessed both before and after tDCS to determine whether stimulation has an effect on this. Each technique is performed on the patient’s first visit and then again following the end of the treatment for both the active and placebo weeks, to determine the effects of tDCS on the brain and to confirm whether visual hallucinations in CBS patients are the result of increased activity in the visual part of the brain.

What are the possible benefits and risks of participating?
This study is trying to find out whether treatment with direct current stimulation reduces visual hallucinations. This will help to develop better treatments. Thousands of people worldwide have undergone direct current stimulation without experiencing any major side effects. Some people experience a tingling sensation with the stimulation, and sometimes a temporary reddening of the skin on the head under the sites where pads are placed during direct current stimulation. Very occasionally, some people may experience a short-lasting headache which can be treated with over-the-counter painkillers. Rarely, some people report feeling sick, have problems sleeping or difficulties with their concentration, although these symptoms are usually short-lived. Sometimes people are also allergic to the electrode pads, but the researchers will check whether participants have had any problems with skin allergies before entering the study. Participants also undergo magnetic stimulation on two occasions, some rare cases have reported some discomfort during stimulation and, occasionally, headaches, but these are also easily treated with painkillers. In extremely rare cases magnetic stimulation has been reported to cause a seizure, but this only seems to have happened in people with a history of seizures. The researchers will check whether participants are at risk of having a seizure or epilepsy before entering the study. EEG is a very safe technique and very few people report any side effects. However, some people may experience temporary redness under electrode pads on the scalp or mild discomfort during electrode set-up. On rare occasions people may experience a headache from the EEG cap or, like with direct current stimulation, may have an allergic reaction to electrode pads or gel. Similarly, magnetic resonance imaging (MRI) is very safe, there is no radiation known to be associated with the scan and the scan is not painful. Some people may feel claustrophobic in the scanner or may experience some discomfort from lying still or flat for a long period of time. Participants are able to leave the scanner at any time they wish and the radiographer performing the scan will communicate with them throughout the scan to check that they are comfortable. Certain medications may exclude people from participating in this study, but this will be assessed before they take part. During participation, participants continue taking their normal medication and are not asked to make any changes.

Where is the study run from?
Newcastle University (UK)

When is the study starting and how long is it expected to run for?
April 2017 to June 2020

Who is funding the study?
1. Macular Society
2. Fight for Sight UK
3. Thomas Pocklington Trust
4. Randerson Foundation
5. NIHR Newcastle University BRC
6. Northumberland, Tyne and Wear NHS Foundation Trust

Who is the main contact?
1. Mrs Kirsty Olsen
2. Ms Kat Da-Silva Morgan

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centre

Sponsor information

Northumberland Tyne & Wear NHS Trust
Hospital/treatment centre

St Nicholas Hospital
Jubilee Road
Gosforth
Newcastle upon Tyne
NE3 3XT
England
United Kingdom

Website	www.ntw.nhs.uk
"ROR"	https://ror.org/01ajv0n48

Funders

Funder type

Charity

Results and Publications

Study outputs

Editorial Notes

26/01/2023: Publication reference added.
01/08/2022: The intention to publish date has been changed from 30/06/2022 to 30/01/2023.
06/07/2022: The study contact has been updated.
17/12/2021: The intention to publish date was changed from 31/12/2021 to 30/06/2022.
18/05/2021: The intention to publish date was changed from 31/05/2021 to 31/12/2021.
07/04/2020: The total final enrolment was added.
27/11/2019: The following changes were made:
1. The recruitment end date was changed from 30/11/2019 to 31/03/2020.
2. The overall trial end date was changed from 29/02/2020 to 30/06/2020.
3. The intention to publish date was changed from 28/02/2021 to 31/05/2021.
16/08/2019: The following changes were made:
1. The recruitment end date was changed from 31/07/2019 to 30/11/2019.
2. The overall trial end date was changed from 31/10/2019 to 29/02/2020.
3. The intention to publish date was changed from 31/10/2020 to 28/02/2021.