Training in Ataxia - Individuals With Degenerative Cerebellar Diseases

The Neural Effects of Balance Versus Aerobic Training in Individuals With Degenerative Cerebellar Diseases

Balance and aerobic training show promise as treatments for degenerative cerebellar diseases, but the neural effects of both training methods are unknown. The goal of this project is to evaluate how each training method impacts the brain, and particularly, the degenerating cerebellum. Various neuroimaging techniques will be used to accomplish this goal and test the hypothesis that balance training impacts brain structures outside the cerebellum whereas aerobic training causes more neuroplastic changes within the cerebellum.

Study Overview

• Status: Active, not recruiting
• Conditions: Cerebellar Ataxia
• Intervention / Treatment: Behavioral: Aerobic Training; Behavioral: Balance Training

Detailed Description

Degenerative cerebellar diseases 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. Balance and aerobic training show promise as treatments for degenerative cerebellar diseases, but the neural effects of both training methods have not been thoroughly investigated. It is crucial to understand how the training impacts the brain, and particularly the cerebellum, in order to determine if one training method is better at slowing disease progression than the other. The goal of this proposal is to compare the neural effects of balance versus aerobic training in individuals with degenerative cerebellar diseases. The investigator hypothesizes that aerobic training causes neuroplastic changes within the cerebellum whereas balance training causes improvements for people with cerebellar degeneration by impacting brain structures outside the cerebellum. If this hypothesis is true, aerobic training may have more influence on disease progression than balance training as it directly impacts the cerebellum.

To investigate the hypothesis, various neuroimaging techniques will be used. In AIM 1, the investigator will compare cerebellar volume before and after the participants perform either 6-months of balance or aerobic training. In AIM 2, the investigator will investigate whether neural changes have clinical significance by correlating cerebellar volume changes with clinical measures of ataxia. Finally, for AIM 3, the investigator will use diffusion tensor imaging and resting state fMRI scans to examine how both training methods impact cerebellar microstructure and functional cerebellar connections. The investigator hopes that a detailed understanding of how each training method impacts the cerebellum will lead to more targeted training regimens with the goal of slowing disease progression of these devastating diseases.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Training; Participants 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. Subjects will record duration of exercise, perceived exertion, average heart rate, maximum heart rate, and distance.	Behavioral: Aerobic Training; Aerobic training on stationary bike 5x a week for 30 minutes a day.
Active Comparator: Balance Training; A physical therapist will tailor a home balance training program for each participant based on pre- training capabilities. Subjects 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.	Behavioral: Balance Training; Balance training 5x a week for 30 minutes as instructed by a therapist. Standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Assessment and Rating of Ataxia (SARA) Score	This is to measure ataxia severity. The Scale for the Assessment and Rating of Ataxia (SARA) will be administered before and after training. SARA is an 8-item performance based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia) - with higher scores indicating ataxia. The scores are based on patient performance of gait, stance, sitting, speech disturbance, finger chase, nose-finger test, fast alternating hand movements and heel-shin slide.	Baseline, 6 months, 9 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average gait speed	This is to measure average time to complete 8-meter walk test. Participants will walk 8 meters as fast as possible three different times. Time will be measured in seconds per meter.	Baseline, 6 months, 9 months, 12 months
Dynamic Gait Index score	The dynamic gait index (DGI) will be performed to asses balance. A four-point ordinal scale, ranging from 0-3. "0" indicates the lowest level of function and "3" the highest level of function. Total Score = 24. Patients will be asked to walk 20 feet and conditions such as speed and head position will be varied as previously described. The examiner will then grade the subject's movement.	Baseline, 6 months, 9 months, 12 months
Prevalence of desired changes in Diffuse Tensor Imaging	Diffusion data will be preprocessed for motion and corrected for geometrical distortion using ExploreDTI. For each participant, the bmatrix will be reoriented to provide a more accurate estimate of diffusion tensor orientations. Diffusion tensor estimation will be performed using a non-linear least square fitting method. FA and Mean Diffusivity (MD) maps will be generated. Whole brain tractography will be performed using all brain voxels with FA ≤ 0.2 as seed region.	6 months
Prevalence of desired changes in Resting State fMRI scans	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.	6 months
Prevalence of Cerebellar Volume	To determine cerebellar volume, each T1 scan will be visually inspected to ensure inclusion of only minimal movement artifacts. All images will be processed in a blinded manner in order to maintain accuracy and consistency of volume calculation. Regional cerebellar volumes will be calculated using the SUIT toolbox of the SPM12 software.	Baseline, 6 months, 9 months, 12 months
Timed Up and Go	The Timed Up and Go will be performed to assess balance. Participants will be asked to stand from seated and then walk around a cone that is 3 meters away. Participants will then walk back to the chair and sit back down. Participants will be timed.	Baseline, 6 months, 9 months, 12 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Scott M Barbuto, MD, Assistant Professor of Rehabilitation and Regenerative Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: exercise; rehabilitation; training; ataxia; cerebellar ataxia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Ataxia; Cerebellar Ataxia; Cerebellar Diseases
• Other Study ID Numbers: AAAT8388

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No