Ignite Creation Date:
2024-05-06 @ 7:53 PM
Last Modification Date:
2024-10-26 @ 3:16 PM
Study NCT ID:
NCT06177626
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-12-20
First Post:
2023-12-11
Brief Title:
Use of a New Smartphone Application to Determine Changes in Eyeblink Conditioning from Home Training in Individuals with Spinocerebellar Ataxia
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
Use of a New Smartphone Application IBlink to Determine Changes in Eyeblink Conditioning from Home Training in Individuals with Spinocerebellar Ataxias
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Spinocerebellar ataxias are a group of disorders that cause severe disability and can be fatal There are currently no known disease-modifying treatments available for use and there is a critical need to find treatments that slow disease progression and allow affected individuals to live more functional lives Aerobic training show promise as a treatment for these diseases but it is unclear if training induces neuroplastic changes within the damaged cerebellum to enhance motor learning or if improvements are primarily caused by changes in leg strength fatigue and endurance It is crucial to understand how the training impacts the brain and particularly the cerebellum in order to determine the most effective training regimen
To examine the impact of aerobic exercise on the brain we propose using eyeblink conditioning a form of motor learning that is dependent on the cerebellum We will utilize BlinkLab a newly developed smartphone application that overcomes the typical barriers of testing eyeblink conditioning by allowing in-home assessments without the need for expensive equipment We hypothesize that 1 individuals with spinocerebellar ataxia will have impaired eyeblink conditioning and 2 aerobic exercise but not balance training will improve eyeblink conditioning in this population If these hypotheses are found to be true it would further support that aerobic exercise is able to enhance motor learning in individuals with cerebellar damage
In AIM 1 we will test eyeblink conditioning in individuals with ataxias and follow them over time to see if eyeblink conditioning might be a biomarker for cerebellar ataxia disease progression We will then use these preliminary results to devise a larger study to further validate eyeblink conditioning as a biomarker for ataxia disease progression In AIM 2 we will determine the impact of training on eyeblink conditioning We expect that aerobic training but not balance training will enhance eyeblink conditioning in spinocerebellar ataxia Finally in AIM 3 we will explore the use of eyeblink conditioning as a biomarker of neuroplasticity
To examine the impact of aerobic exercise on the brain we propose using eyeblink conditioning a form of motor learning that is dependent on the cerebellum We will utilize BlinkLab a newly developed smartphone application that overcomes the typical barriers of testing eyeblink conditioning by allowing in-home assessments without the need for expensive equipment We hypothesize that 1 individuals with spinocerebellar ataxia will have impaired eyeblink conditioning and 2 aerobic exercise but not balance training will improve eyeblink conditioning in this population If these hypotheses are found to be true it would further support that aerobic exercise is able to enhance motor learning in individuals with cerebellar damage
In AIM 1 we will test eyeblink conditioning in individuals with ataxias and follow them over time to see if eyeblink conditioning might be a biomarker for cerebellar ataxia disease progression We will then use these preliminary results to devise a larger study to further validate eyeblink conditioning as a biomarker for ataxia disease progression In AIM 2 we will determine the impact of training on eyeblink conditioning We expect that aerobic training but not balance training will enhance eyeblink conditioning in spinocerebellar ataxia Finally in AIM 3 we will explore the use of eyeblink conditioning as a biomarker of neuroplasticity
Detailed Description:
Spinocerebellar ataxias are a group of disorders that cause severe disability due to progressive incoordination With no FDA approved medications there is a critical need to find effective treatments12 Our research team has shown that high intensity aerobic training defined as 30-minute training sessions 5x per week at above 80 maximum heart rate is a potential treatment causing clinically significant improvements in ataxia symptoms at 6-months compared to home balance training3-5 However it is unclear whether aerobic training induces neuroplastic changes within the damaged cerebellum or if improvements are primarily due to increased leg strength and endurance which help compensate for ataxia and balance deficits6 We hypothesize that aerobic training causes improvements for people with spinocerebellar ataxias by inducing neuroplastic changes within the cerebellum whereas balance training does not Our hypothesis is supported by 1 Research that balance training in individuals with spinocerebellar ataxia causes increased grey matter volume in the premotor cortex but no statistically significant changes in the cerebellum7 2 Although not verified in humans aerobic exercise rescues motor coordination deficits in ataxic mice and improvements correlate with restored cerebellar BDNF levels8 3 TrkB the BDNF receptor was vital for improved motor function and reduced Purkinje cell degeneration seen in ataxic rats that performed endurance exercise9 Thus we propose that aerobic training increases cerebellar BDNF levels which enhances responsivity to neurotransmitters and downregulates GABA-inhibition10-14 This response in turn leads to a fertile environment in the cerebellum with one consequence being improved motor learning1516 In order to investigate the impact of aerobic training on cerebellar dependent motor learning we propose using eyeblink conditioning In this task individuals learn to blink in response to a conditioned stimulus that is paired with an unconditioned stimulus Unfortunately eyeblink conditioning is costly requires multiple in-person visits to measure learning and produces data that necessitates extensive programing and data management skills to interpret To overcome these barriers our collaborators recently developed BlinkLab an application for the smartphone that can test eyeblink conditioning remotely This application is low cost straight-forward for participants to use at home and produces easily interpretable data Moreover our research team has shown that BlinkLab can be used to determine changes in eyeblink conditioning due to aerobic training in healthy individuals Thus the goal of this pilot study will be to use the BlinkLab application to study the impact of exercise on eyeblink conditioning serving as a proxy for neuroplastic changes within the cerebellum
Aim 1 To determine if eyeblink conditioning is a useful biomarker for spinocerebellar ataxias Our preliminary work with BlinkLab indicates that individuals with ataxia have deficits in eyeblink conditioning compared to healthy controls We will recruit 40 individuals with spinocerebellar ataxia and compare changes in ataxia symptoms to changes in eyeblink conditioning over 6-months We hypothesize that eyeblink conditioning will worsen as disease progresses
Aim 2 Impact of aerobic exercise on eyeblink conditioning in spinocerebellar ataxias Thirty individuals with spinocerebellar ataxias will be randomized to either home balance or aerobic training for 3-months Participants will undergo eyeblink conditioning using BlinkLab at baseline 3- and 4-months Secondary outcome measures will include ataxia severity leg strength endurance fitness balance and abilities to do activities of daily living We hypothesize that individuals in the aerobic group will have improved eyeblink conditioning compared to the balance training group Furthermore we expect that improvements in ataxia symptoms will correlate with improvements in eyeblink conditioning
Exploratory Aim 3 Correlation of eyeblink conditioning changes induced by aerobic training with functional connectivity changes in the cerebellum Resting state fMRI scans will be taken before and after individuals with spinocerebellar ataxia participate in the 3-month training programs in Aim 2 We will then use the cerebellum as our region of interest to analyze how training impacts functional cerebellar connections17-22 We will explore the relationship between eyeblink conditioning and functional cerebellar changes caused by training to assess the use of eyeblink conditioning as a biomarker of neuroplasticity
Aim 1 To determine if eyeblink conditioning is a useful biomarker for spinocerebellar ataxias Our preliminary work with BlinkLab indicates that individuals with ataxia have deficits in eyeblink conditioning compared to healthy controls We will recruit 40 individuals with spinocerebellar ataxia and compare changes in ataxia symptoms to changes in eyeblink conditioning over 6-months We hypothesize that eyeblink conditioning will worsen as disease progresses
Aim 2 Impact of aerobic exercise on eyeblink conditioning in spinocerebellar ataxias Thirty individuals with spinocerebellar ataxias will be randomized to either home balance or aerobic training for 3-months Participants will undergo eyeblink conditioning using BlinkLab at baseline 3- and 4-months Secondary outcome measures will include ataxia severity leg strength endurance fitness balance and abilities to do activities of daily living We hypothesize that individuals in the aerobic group will have improved eyeblink conditioning compared to the balance training group Furthermore we expect that improvements in ataxia symptoms will correlate with improvements in eyeblink conditioning
Exploratory Aim 3 Correlation of eyeblink conditioning changes induced by aerobic training with functional connectivity changes in the cerebellum Resting state fMRI scans will be taken before and after individuals with spinocerebellar ataxia participate in the 3-month training programs in Aim 2 We will then use the cerebellum as our region of interest to analyze how training impacts functional cerebellar connections17-22 We will explore the relationship between eyeblink conditioning and functional cerebellar changes caused by training to assess the use of eyeblink conditioning as a biomarker of neuroplasticity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None