Feasibility of Neuromodulation With Connectivity-Guided iTBS for Cognitive Impairment in MS

Summary

Cognitive difficulties can affect many people who live with multiple sclerosis (MS). These difficulties, such as within thinking, memory, and problem solving, can have an impact on important aspects of an individual's life, including their daily activities, work, and how they manage their condition. Previous studies have suggested that cognitive difficulties affect approximately 40-70% of people living with MS, yet there are currently no treatments to target these problems. Recent research has directed towards a non-invasive intervention which stimulates a part of the brain (called the dorsolateral prefrontal cortex, or DLPFC for short) which is reported to participate in cognitive processes, such as memory, thinking, and attention. This intervention, called "intermittent theta burst stimulation" (iTBS), involves placing a magnetic device to the skull to activate the DLPFC underneath. This technique has been used successfully in the treatment of depression and is widely considered safe and painless. Previous studies have also shown that iTBS intervention can lead to improvements in cognitive processes.

Before the investigators can progress to a large trial to explore its clinical effectiveness for reducing cognitive problems for people with MS, some aspects regarding its feasibility need to be clarified, for example whether it is an acceptable and tolerable intervention for people living with MS. A single-centre, mixed methods feasibility randomised controlled trial will be conducted to compare four groups (10 participants each) of iTBS administration. At baseline, End of Intervention (EOI), and 8-week follow up, the investigators will complete outcome measures to evaluate cognition, mood and fatigue. Participants will also undergo MRI scans at baseline and EOI. Following participation, participants will be interviews and the investigators will organise a post-participation workshop to explore their experiences of the trial, including the tolerability of the protocol and acceptability of the visit schedule, and any differences in cognition.

Conditions

• Multiple Sclerosis
• Cognitive Impairment

Interventions

OTHER

Intermittent theta burst stimulation (iTBS)

The localisation of the left dorsolateral prefrontal cortex (DLPFC) target will be identified using effective connectivity of the left caudate to identify the maximally-connected locus in the left DLFPC. Following this the iTBS will be administered to the target coordinates identified using the neuronavigation software available with the system. Connectivity-guided iTBS is then administered using a 70mm Double Air Film Coil (Magstim, Whitland, Dyfed, UK), connected to a Magstim Super Rapid-2 Plus-1 stimulator. The administration comprises bursts of 3 pulses at 50Hz with a power of 80% motor threshold at a burst frequency of 5 Hz (i.e., every 200ms) for 2 seconds, repeated every 10 seconds for a total of 190 seconds (600 pulses). Blocks are repeated a total of 3 times, with 5-minute rest intervals between blocks. During left DLPFC stimulation, the TBS coil is held by a support tangentially to the skull, with the axis of the coil angled approximately 90 degrees from the midsagittal axis.

OTHER

Sham Intermittent theta burst stimulation (iTBS)

The sham iTBS administration is performed under the same conditions and with an identical protocol and equipment to the full administration, except that it uses a commercially available sham iTBS coil designed for use in double-blind trials. This sham coil looks like the real coil and connects to the iTBS unit but delivers only a very weak and shallow stimulation thus simulating the sounds made by the real iTBS coil.

Sponsors & Collaborators

• University of Nottingham

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

69 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-01

Primary Completion

2023-08-31

Completion

2023-12-31

Countries

• United Kingdom

Study Locations