Impact of Exercise on Eyeblink Conditioning in Spinocerebellar Ataxias

Spinocerebellar Ataxias Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06177626
• Other study ID #: AAAV0188 (Aim 3)
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: September 1, 2026

Study information

• Verified date: December 2023
• Source: Columbia University
• Contact: Scott Barbuto, MD, PhD
• Phone: 212-305-3535
• Email: sb3779[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this project is to evaluate how aerobic training impacts eyeblink conditioning as a proxy for cerebellar dependent motor learning. The newly developed smartphone application, iBlink, will be used to test participants at home in an effort to improve recruitment and increase the sample size of the study. The investigators hypothesize that aerobic training, but not balance training, will improve eyeblink conditioning in participants with spinocerebellar ataxias. The current study focuses on Aim 3 of this project.

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, 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 training. However, it is unclear whether aerobic training induces neuroplastic changes within the damaged cerebellum to enhance motor learning, or if improvements are primarily due to increased leg strength and endurance which help compensate for balance deficits.

In order to investigate the impact of aerobic training on cerebellar-dependent motor learning, the research team proposes using eyeblink conditioning. In this paradigm, an unconditioned stimulus, such as a flash of light, is used to elicit a reflexive blink. When a neutral conditioned stimulus, such as a tone is paired repeatedly with the flash of light, individuals learn to blink their eyes in response to the tone (conditioned response). The magnitude of learning is gauged by the percentage of trials that result in a conditioned response or the mean change in conditioned response amplitude. Unfortunately, eyeblink conditioning is not often utilized in clinical studies due to the high cost, extensive programing and data management skills needed to interpret data, and the need for multiple in-person visits to ascertain the magnitude of learning.

In an effort to overcome these barriers, the research team's collaborators recently developed iBlink, 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 iBlink 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 iBlink application to study the impact of exercise on eyeblink conditioning as a proxy for motor learning in spinocerebellar ataxias.

Aim 1) To determine if individuals with spinocerebellar ataxias have deficits in eyeblink conditioning using iBlink. Prior studies indicate that individuals with spinocerebellar ataxia 3, 6, and Fredrich's ataxia have impaired eyeblink conditioning, but it is unclear whether this is true for other ataxia types. Thus, the investigators will recruit individuals with a variety of spinocerebellar ataxia types and compare eyeblink conditioning to age and sex-matched healthy controls (baseline condition). The investigators hypothesize that all participants with spinocerebellar ataxia will have impaired eyeblink conditioning compared to healthy controls, but participants with spinocerebellar ataxia types that cause oculomotor deficits will have more impairment than individuals with other ataxia types.

Aim 2) Impact of acute aerobic exercise on eyeblink conditioning in spinocerebellar ataxias. Acute aerobic exercise enhances the conditioned response rate in healthy individuals, and this enhancement is larger in physically active individuals when compared to sedentary people. For this study, participants with spinocerebellar ataxia will be classified as sedentary or physically active using the Global Physical Activity Questionnaire. Next, participants will be asked to perform 30-minutes of acute aerobic training at moderate intensity (~75% max heart rate) for 5 consecutive days. Immediately after each training, participants will use iBlink and results will be compared to baseline condition (Aim 1). The investigators hypothesize that all participants with ataxia will have improvement in eyeblink conditioning (increased mean change in conditioned response amplitude) after acute aerobic training, but those who are more physically active will have more enhancement with exercise.

Aim 3) Impact of long-term aerobic exercise on eyeblink conditioning in spinocerebellar ataxias. Participants will be randomized to either home balance or aerobic training for 6-months. Participants will undergo eyeblink conditioning using iBlink at baseline, 3-, 6-, and 9-months. Ataxia symptoms will also be determined using the remote video Scale for the Assessment and Rating of Ataxia (SARAhome) at each assessment. 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 SARA scores will correlate with improvements in eyeblink conditioning, supporting that the aerobic training is inducing neuroplastic changes within the cerebellum.

Clinical Significance: Aerobic training demonstrates promise as a treatment for spinocerebellar ataxias, but the mechanism of improvement is unclear. This study addresses if aerobic training can enhance motor learning in individuals with cerebellar degeneration. It will also help validate the use of the iBlink application as an easy, inexpensive, and remote way to test eyeblink conditioning. Thus, eyeblink conditioning can be more readily used to monitor spinocerebellar ataxias or be used as an outcome measure in future clinical studies.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: September 1, 2026
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Diagnosed with spinocerebellar ataxia

• Cerebellar atrophy on MRI

• Prevalence of ataxia on clinical exam

• Ability to safely ride a stationary exercise bike

Exclusion Criteria:

• Other neurologic conditions

• Heart disease

• Cognitive impairment

• Medical instability

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Intervention

Behavioral:
• Aerobic Training
Aerobic training on stationary bike 5x a week for 30 minutes a day
• Balance Training
Training 5x a week for 30 minutes. Standard of care.

Locations

Country	Name	City	State
United States	Columbia University/New York Presbyterian	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	0, 3, 6, and 9 months
Secondary	SARAhome Score	Scale for the Assessment and Rating of Ataxia Home (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 as a result of training.	0, 3, 6, and 9 months
Secondary	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.	0, 3, 6, and 9 months