AzTrials
AzTrials

Spinocerebellar AtaxiasNCT06177626

Use of a New Smartphone Application to Determine Changes in Eyeblink Conditioning From Home Training in Individuals With Spinocerebellar Ataxia

A study testing Aerobic Training and Balance Training in people with Spinocerebellar Ataxias, run by Columbia University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Spinocerebellar Ataxias
What is being tested?
Aerobic Training and Balance Training
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2026to Oct 2027
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Diagnosed with spinocerebellar ataxia
  • Cerebellar atrophy on MRI
  • Prevalence of ataxia on clinical exam (SARA >2)
  • Ability to safely ride a stationary exercise bike (SARA sitting sub-score <3)

Who cannot join

  • Parkinson's Disease
  • Traumatic Brain Injury
  • Stroke
  • Alzheimer's Disease
  • Heart disease
  • Dementia
  • Medical instability
  • Inability to walk without assistance (SARA gait sub-score >6).

About this study

Official title: Use of a New Smartphone Application, iBlink, to Determine Changes in Eyeblink Conditioning From Home Training in Individuals With Spinocerebellar Ataxias

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, this study proposes using eyeblink conditioning, a form of motor learning that is dependent on the cerebellum. This study 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. The investigators 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, investigators 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. The investigators will then use these preliminary results to devise a larger study to further validate eyeblink conditioning as a biomarker for ataxia disease progression. Aim 2 will determine the impact of training on eyeblink conditioning. The investigators expect that aerobic training, but not balance training, will enhance eyeblink conditioning in spinocerebellar ataxia. Finally, Aim 3 will explore the use of eyeblink conditioning as a biomarker of neuroplasticity.

Read the 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 treatments. The research team has shown that high intensity aerobic training, defined as 30-minute training sessions, 5 times 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 training. 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 deficits.

The investigators hypothesize that aerobic training causes improvements for people with spinocerebellar ataxias by inducing neuroplastic changes within the cerebellum whereas balance training does not. The 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 cerebellum. 2) Although not verified in humans, aerobic exercise rescues motor coordination deficits in ataxic mice and improvements correlate with restored cerebellar BDNF levels. 3) TrkB, the BDNF receptor, was vital for improved motor function and reduced Purkinje cell degeneration seen in ataxic rats that performed endurance exercise. Thus, this study proposes that aerobic training increases cerebellar BDNF levels which enhances responsivity to neurotransmitters and downregulates GABA-inhibition. This response, in turn, leads to a fertile environment in the cerebellum with one consequence being improved motor learning.

In order to investigate the impact of aerobic training on cerebellar dependent motor learning, this study will use 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, the study 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, the 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. Preliminary work with BlinkLab indicates that individuals with ataxia have deficits in eyeblink conditioning compared to healthy controls. The study will recruit 40 individuals with spinocerebellar ataxia and compare changes in ataxia symptoms to changes in eyeblink conditioning over 6-months. The investigators 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. The investigators hypothesize that individuals in the aerobic group will have improved eyeblink conditioning compared to the balance training group. Furthermore, the investigators 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. Investigators will then use the cerebellum as the region of interest to analyze how training impacts functional cerebellar connections. Investigators 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.

Being tested
Aerobic Training, Balance Training
Keywords
Ataxia, Eyeblink Conditioning, Exercise
Medical subject headings
Spinocerebellar Ataxias, Ataxia, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aerobic TrainingBehavioural

    Aerobic training on stationary bike 5x a week for 30 minutes a day

  • Balance TrainingBehavioural

    Training 5x a week for 30 minutes. Standard of care.

Study groups in NCT06177626
Study groupRoleWhat they receive
Balance TrainingActive comparatorA physical therapist will tailor a home balance training program for each participant based on pre- training capabilities. Participants will be asked to perform exercises five times a week for thirty-minute sessions. Both dynamic and static exercises will be performed in sitting and standing positions. Exercises will start with stabilizing in a challenging static position and progress to dynamic arm and leg movements in the same or modified position. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be required to log their exercise effort in terms of frequency and level of balance challenge.
Receives: Behavioral: Balance Training
Aerobic TrainingExperimentalParticipants will be given a stationary exercise bike for home use. They will be instructed to use the exercise bike five times a week for thirty-minute sessions. The exercise intensity prescription will be based on the subject's VO2max determined on pre-test day. The exercise program will start at 60% of intensity per session, and then will be increased by steps of 5% intensity every 2 sessions until participants reach 30 minutes of training at 80% intensity. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be instructed to log each training session. Participants will record duration of exercise, perceived exertion, average heart rate, maximum heart rate, and distance.
Receives: Behavioral: Aerobic Training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Conditioned Response (CR) Amplitude

    Individual eyelid traces will be normalized by dividing each trace by the maximum signal amplitude of the relevant session. Thus, eyes closed will correspond to a value of 1, and eyes open to a value of 0. A mean baseline Conditioned Response (CR) amplitude will be determined for each participant using the pre-block Conditioned Stimulus (CS) only trials. CR amplitude will then be determined as the maximum signal amplitude value at 430ms, for paired and CS only trials, minus the baseline CR amplitude.

    Measured: 0, 3, and 4 months

Secondary outcomes (7)
  1. Scale for the Assessment and Rating of Ataxia (SARA)

    SARA is a validated clinical measure of ataxia severity. Scores range from 0 to 40 with higher scores indicating more ataxia symptoms. Each SARA test will be recorded and the order scrambled to blind researchers to time of testing. This test has a sensitivity of 0.99 and specificity of 0.96. Interrater reliability, test-retest reliability, and internal consistency was also determined to be high. SARAhome is a validated home measurement of ataxia symptoms with the participants recording 5 tasks (gait, stance, speech, nose-finger test, and fast alternating hand movements) with a smartphone. Scores range from 0 to 28 with higher scores indicating more ataxia symptoms. SARAhome and the conventional SARA were shown to be highly correlated, and this measurement was deemed reliable for home monitoring of ataxia symptoms. Scores will be used to correlate with changes in eyeblink conditioning in Aim 1.

    Measured: 0, 3, and 4 months

  2. PROM of Ataxia Score

    The Patient Reported Outcome Measure (PROM) of Ataxia is a 70-item survey that is scored by participants on a 0-4 Likert scale. It asks participants to rate motor domains of gait, lower and upper extremity control, manual dexterity, visual motor control, dysphagia, bowel and bladder function, sleep, fatigue, vertigo, libido, neuropathy, ability to do household chores, driving, self-care, mood, anxiety, motivation, and social interactions. Scores will be used to correlate with changes in eyeblink conditioning as a result of training. Scores range from 0-280 with a higher score indicating a worse outcome.

    Measured: 0, 3, and 4 months

  3. Quantitative Muscle Testing (QMT)

    QMT has been shown to have excellent intra-rater and inter-rater reliability for the measurement of leg strength. Knee extensor and flexor strength will be determined by measuring maximal voluntary isometric contraction using QMT (Aeverl Medical, Gainesville, GA). This system consists of an adjustable strap, attaching the legs to interface force transducers. Subjects will be tested on an adjustable examination table that anchors the transducer. The generated force is transmitted to an electronic strain-gauge tensiometer and is then recorded and amplified by the data computer-assisted analog to digital acquisition system.

    Measured: 0, 3, and 4 months

  4. 6-minute Walk Test (6MWT)

    The 6MWT is a validated measure of endurance. Individuals will be instructed to walk as far as they can on a 30-meter walkway. It was deemed to have excellent reliability.

    Measured: 0, 3, and 4 months

  5. Balance Measures

    To monitor balance, the Timed Up and Go (TUG) test will be performed according to standard protocols. Participants will also perform the Dynamic Gait Index (DGI) using the established protocol. Scores on the DGI range from 0 to 24 with lower scores indicating more severe problems with balance and increased risk of falling. Although not determined on individuals with spinocerebellar ataxia, a minimal clinically important difference of 1.9 points was determined for community-dwelling older adults.

    Measured: 0, 3, and 4 months

  6. Maximal Oxygen Consumption (VO2Max)

    Results from CPET at initial testing will be used to develop training programs for those randomized to the aerobic group. It will also be used as a secondary outcome for Aim 2. Maximal oxygen consumption (VO2max) will be determined by a breath-by-breath measurement of VO2 with a Vmax Encore Metabolic System, while participants perform a progressive ramped exercise test using an electronic-braked lower body cycle ergometer (CareFusion Corp, San Diego, CA).

    Measured: 0, 3, and 4 months

  7. Maximal Oxygen Consumption (VO2Max)

    Resting State Functional MRI: This measure will be a primary outcome for Aim 3. The anatomical and functional data will be pre-processed and analyzed using Statistical Parametric Mapping (SPM12) and the CONN toolbox Version 14p. Functional data will be pre-processed using a slice scan time correction, realignment (motion correction), registration to structural images and spatial normalization to Montreal Neurological Institute (MNI) standardized space, smoothing with a Gaussian filter of 5.0 mm spatial full width at half maximum value. A conventional band-pass filter over a low-frequency window of interest (0.008-0.09) will also be applied to the resting-state time series. After these preprocessing steps, we will extract signal to noise from the white matter and cerebrospinal fluid by principal component analysis without affecting intrinsic functional connectivity.

    Measured: 0 and 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2023
  2. Study startJan 2026 (estimated)
  3. Primary completionJul 2027 (estimated)
  4. Study completionOct 2027 (estimated)

Why it stopped: Lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Single blinded randomized controlled trial
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06177626
Sponsor's protocol ID
AAAV2412 (Aim 2 and 3)
Status last verified
May 2026
First submitted
11 Dec 2023
Last updated
7 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Aerobic Training and Balance Training in people with Spinocerebellar Ataxias, run by Columbia University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Conditioned Response (CR) Amplitude (time frame: 0, 3, and 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in