Brief Title
Mechanism of Action of Transcranial Direct Current Stimulation in Neurofibromatosis Type 1
Official Title
Mechanism of Action of Transcranial Direct Current Stimulation in Neurofibromatosis Type 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.
Study Type
Interventional
Primary Outcome
Corsi Block task
Condition
Neurofibromatosis 1
Intervention
Transcranial direct current stimulation
Study Arms / Comparison Groups
Active trancranial direct current stimulation
Description: Active stimulation for 15 minutes
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
31
Start Date
February 22, 2019
Completion Date
February 19, 2020
Primary Completion Date
February 19, 2020
Eligibility Criteria
Inclusion Criteria:
1. Meets National Institute of Health NF1 diagnostic criteria
2. Children aged 11-17 years
3. Written informed consent/assent
Exclusion Criteria:
1. No history of intracranial pathology other than asymptomatic optic pathway glioma or
other asymptomatic and untreated NF1-associated white matter lesion
2. No history of epilepsy or any major mental illness
3. No MRI contraindications.
Gender
All
Ages
11 Years - 17 Years
Accepts Healthy Volunteers
No
Contacts
, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT04991428
Organization ID
18/NW/0762
Responsible Party
Principal Investigator
Study Sponsor
University of Manchester
Study Sponsor
, ,
Verification Date
July 2021