Exercise for Spinocerebellar Ataxias

Overseen By Scott Barbuto, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Parkinson's, Stroke, Alzheimer's, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for Spinocerebellar Ataxias?

Research shows that aerobic training can significantly improve symptoms of ataxia, as seen in a study where participants with cerebellar ataxia experienced better outcomes compared to those who only did balance training. Additionally, physical rehabilitation, including aerobic exercise, has been shown to improve balance, gait, and daily activities in patients with spinocerebellar ataxia. ^{1 2 3 4 5}

Is exercise safe for people with spinocerebellar ataxias?

Research shows that aerobic and balance training for people with cerebellar ataxia, including spinocerebellar ataxias, is generally safe. In a study, participants experienced no serious adverse events, and minor issues like falls or back pain did not interrupt training. ^{1 3 6 7 8}

How does the exercise treatment for spinocerebellar ataxias differ from other treatments?

This exercise treatment is unique because it focuses on home aerobic training, which has shown significant improvement in ataxia symptoms compared to balance training. Unlike other treatments, it emphasizes aerobic exercises that can be done at home, making it more accessible and potentially more effective in improving symptoms of spinocerebellar ataxias. ^{1 2 3 4 9}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals with Spinocerebellar Ataxias and related conditions who can perform physical exercises. The study aims to understand if exercise can improve certain brain-related learning processes.

Inclusion Criteria

I can safely use a stationary exercise bike.

I have been diagnosed with spinocerebellar ataxia.

Cerebellar atrophy on MRI

Exclusion Criteria

Medical instability

I have a neurological condition.

I have a heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including eyeblink conditioning using BlinkLab and other secondary outcome measures

1 week

1 visit (in-person)

Treatment

Participants are randomized to either home balance or aerobic training for 3 months, with weekly check-ins

12 weeks

Weekly virtual check-ins

Post-Treatment Assessment

Participants undergo post-treatment assessments including eyeblink conditioning and secondary outcome measures

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in eyeblink conditioning and ataxia symptoms

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Aerobic Training
• Balance Training

Trial Overview The study tests whether aerobic training, compared to balance training, enhances a type of learning linked to the cerebellum in the brain. Participants will use an app called iBlink at home to measure outcomes.

Participant Groups

Group I: Aerobic Training Experimental Treatment 1 Intervention

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. Participants will record duration of exercise, perceived exertion, average heart rate, maximum heart rate, and distance.

Group II: Balance Training Active Control 1 Intervention

A 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.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Findings from Research

Rehabilitation interventions for spinocerebellar ataxia showed significant improvements in balance and gait, with statistical significance for posture (P<.008) and gait (P<.02).

The interventions also led to notable reductions in speech disorders (P=.02), depressive symptoms (P<.0001), and accidental falls (P<.005), indicating a broader impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of physical rehabilitation in patients with hereditary spinocerebellar ataxia. A systematic review]. Marchal-Muñoz, A., García-Aranda, M., Marchal-Muñoz, M., et al.[2021]

A 38-year-old man with Friedreich ataxia showed significant improvements in aerobic capacity after a medically supervised endurance training program, with a 27% increase in peak VO2 and a 21% increase in peak ventilation.

The training led to a 50-watt increase in maximum workload and a total exercise time increase of five minutes, along with a weight loss of 4.75 kg, indicating that aerobic conditioning can be beneficial for patients with FA who are able to engage in cycling exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endurance exercise training in Friedreich ataxia. Fillyaw, MJ., Ades, PA.[2006]

The article provides evidence-based exercise guidelines for individuals with multiple sclerosis, stroke, and Parkinson disease, emphasizing the importance of both aerobic and resistance training.

For multiple sclerosis, the recommended regimen is 2-3 days per week of aerobic training (10-30 minutes at moderate intensity) and 2-3 days of resistance training (1-3 sets of 8-15 repetitions). Stroke guidelines suggest 3-5 days of aerobic training (20-40 minutes) and similar resistance training, while Parkinson disease guidelines recommend 3-5 days of aerobic training (20-60 minutes) and resistance training (1-3 sets of 8-12 repetitions).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Training Guidelines for Multiple Sclerosis, Stroke, and Parkinson Disease: Rapid Review and Synthesis. Kim, Y., Lai, B., Mehta, T., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Home Aerobic Training for Cerebellar Degenerative Diseases: a Randomized Controlled Trial. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

[Effect of physical rehabilitation in patients with hereditary spinocerebellar ataxia. A systematic review]. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of Physical Rehabilitation in Patients with Spinocerebellar Ataxia Type 7. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Partial Body Weight-Supported Treadmill Training in Spinocerebellar Ataxia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Challenge of neurorehabilitation for cerebellar degenerative diseases. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A randomized controlled pilot trial of game-based training in individuals with spinocerebellar ataxia type 3. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Endurance exercise training in Friedreich ataxia. [2006]

8. United States pubmed.ncbi.nlm.nih.gov

Exercise Training Guidelines for Multiple Sclerosis, Stroke, and Parkinson Disease: Rapid Review and Synthesis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Update on intensive motor training in spinocerebellar ataxia: time to move a step forward? [2021]