Mechanism of Action of Transcranial Direct Current Stimulation in Neurofibromatosis Type 1

NCT04991428 | Completed

• 1 other identifier: 18/NW/0762
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Intellectual impairment, particularly working memory deficits are a significant cause of morbidity in children with Neurofibromatosis type (NF1) with long-term implications on academic and occupational functioning. Whilst significant discoveries have been made in Nf1 animal models in trying to find treatments for these conditions, human translational studies have not been successful. This mechanistic experimental study will investigate the neural mechanisms underlying working memory deficits in NF1. In particular, we will investigate how individual differences in inhibitory neurotransmitter GABA relate to performance on working memory tests. Further, we will investigate the use of a novel, experimental intervention called transcranial Direct Current Stimulation (tDCS);known to modulate GABA. Using a randomized, crossover design in a cohort of 30 adolescents aged 11-17 years, we will apply real or sham tDCS to the dorsolateral prefrontal cortex (DLPFC). State-of-art real time imaging techniques such as Magnetic Resonance Spectroscopy (MRS) and task based functional MRI (fMRI) will be used to investigate the effect of tDCS on GABA concentration, changes in functional plasticity and working memory. We expect that results from this study will help elucidate the neural mechanisms underlying working memory deficits in people with NF1 and show biologic activity for a novel, low-cost intervention that can be used for cognitive remediation in NF1. This kind of focused mechanism trial method is a highly promising approach to understanding the complex neural system pathology in a multifactorial neurodevelopmental condition like NF1.

Conditions

Neurofibromatosis 1

Outcome Measures

Primary Outcomes (1)

• Corsi Block task

  memory span task

  immediately after the intervention

Study Arms (2)

Active trancranial direct current stimulation

EXPERIMENTAL

Active stimulation for 15 minutes

Other: Transcranial direct current stimulation

Sham stimulation

SHAM COMPARATOR

Similar set-up but no actual stimulation

Other: Transcranial direct current stimulation

Interventions

Transcranial direct current stimulation OTHER

tDCS is a form of non-invasive brain stimulation. tDCS is an established research tool for non-invasive modulation of neuroplasticity. It uses low-intensity DC currents to modulate spontaneous neuronal network activity by altering the resting membrane potential. Anodal tDCS has been shown to increase cortical excitability, reduce regional levels of GABA enhance LTP and synaptic plasticity.

Active trancranial direct current stimulation; Sham stimulation

Eligibility Criteria

• Age: 11 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Meets National Institute of Health NF1 diagnostic criteria
• Children aged 11-17 years
• Written informed consent/assent

You may not qualify if:

• No history of intracranial pathology other than asymptomatic optic pathway glioma or other asymptomatic and untreated NF1-associated white matter lesion
• No history of epilepsy or any major mental illness
• No MRI contraindications.

Sponsors & Collaborators

• University of Manchester: lead

Study Sites (1)

University of Manchester

Manchester, Greater Manchester, M13 9QQ, United Kingdom

Location

MeSH Terms

Conditions

Neurofibromatosis 1

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Senior Lecturer

Model Details: Single-blind cross over experimental trial

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 5, 2021
• Study Start: February 22, 2019
• Primary Completion: February 19, 2020
• Study Completion: February 19, 2020
• Last Updated: August 5, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be made available upon request.

Locations

GB (1)