Palsy Supranuclear, Supranuclear Palsy, Progressive
Conditions
Keywords
repetitive transcranial magnetic stimulation
Brief summary
The objective of this proposal is to investigate the effect of non-invasive repetitive cerebellar transcranial magnetic stimulation (rTMS) on motor control in progressive supranuclear (PSP). The central hypothesis is that augmenting cerebellar inhibition via cerebellar rTMS will decrease postural instability in patients with PSP. We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS.
Interventions
DEVICERepetitive transcranial magnetic stimulation (rTMS)
Aim 1: To determine the clinical effects of rTMS targeting the cerebellum on postural instability in PSP. The hypothesis to be tested is that TMS augmentation of cerebellar inhibition will improve cerebellum-dependent balance symptoms of PSP for a period of time sufficient to improve rehabilitation outcomes. The investigators will measure a battery of objective posturography metrics and other measures of motor control, including sway and center of pressure changes to backward tilt and forward translation. Aim 2: We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS. The hypothesis to be tested is that premotor and motor cortical activity will decrease after cerebellar rTMS compared to sham TMS, reflecting improved cerebellar inhibition of the motor cortex after the intervention.
Sponsors
National Center of Neuromodulation for Rehabilitation
Collins Medical Trust
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Department of Health and Human Services
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Advancing Translational Sciences (NCATS)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
The subjects will be blinded to the order of intervention, but the PI will not be blinded in order to perform the TMS intervention. The outcome evaluators will be blinded to the intervention, however.
Intervention model description
The investigators will use a single-blind crossover design with a 4 week TMS washout period. The subjects will serve as their own controls, thus limiting confounding variables such as medication or cognitive effect.
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* probable or possible PSP by the revised MDS PSP Criteria (Hoglinger 2017) * age 40-85 at time of screening * ability to understand and cooperate with simple instructions in English * ability to read at 6th grade reading level in English * ability to stand unassisted for at least 30 seconds and to be able walk independently with a walker * ability to refrain from new physical and speech therapy programs for the duration of the study * ability to remain on stable doses of any cholinergic, dopaminergic, serotonergic sedative or NMDA receptor antagonists for the duration of the study * females of child-bearing age must perform a urine pregnancy test and be on reliable birth control during the course of the study
Exclusion criteria
* other significant neurological or vestibular disorders * presence of electrically, magnetically or mechanically activated implants or history of injurious metal exposure in eyes, head, or body
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| objective posturography | assessed on 4 days during the 8 week study period | The primary endpoint is center of pressure shifts with tilt and with translation, and body sway in quiet stance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| fNIRS | assessed on 4 days during the 8 week study period | functional near infrared spectroscopy of premotor and motor areas during balance testing |
| speech analysis | assessed on 4 days during the 8 week study period | speech sample assessment conducted by investigator |
Countries
United States
Contacts
Primary ContactGraham Harker
Outcome results
None listed