Respiratory Training for Friedreich's Ataxia

Overseen By Julia Prascak, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must not be taking: Antibiotics, Corticosteroids, Neuromuscular agents

Disqualifiers: Allergy to lidocaine, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether respiratory strength training can help individuals with Friedreich's Ataxia, a rare genetic disorder affecting balance, coordination, and muscle strength. Participants will use a special breathing device at home up to five times a week for 12 weeks to determine if it improves their breathing and swallowing abilities. The trial seeks individuals with confirmed Friedreich's Ataxia who experience swallowing issues. As an unphased trial, this study provides a unique opportunity to contribute to understanding potential new therapies for managing symptoms of Friedreich's Ataxia.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have taken antibiotics, systemic corticosteroids, or neuromuscular blocking agents within 15 days before the baseline screening.

What prior data suggests that this respiratory strength training is safe for patients with Friedreich's Ataxia?

Research has shown that respiratory strength training is generally safe and well-tolerated by participants. This training includes exercises to strengthen the muscles used for breathing. Previous studies have not reported any major side effects from this type of training. Most participants manage the exercises well, with few safety concerns. Although specific safety data for respiratory training in Friedreich's Ataxia is lacking, it resembles other physical therapies safely used for various conditions. Overall, evidence suggests it is a safe option for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Respiratory Strength Training (RST) for Friedreich's Ataxia because it introduces a non-pharmacological approach to managing respiratory issues associated with the condition. Unlike standard treatments that often focus on symptom management or slowing disease progression through medications, RST empowers patients to actively strengthen their respiratory muscles using a specialized device at home. This novel method could improve breathing function and quality of life without the need for additional drugs, offering a new avenue of hope for patients with Friedreich's Ataxia.

What evidence suggests that respiratory strength training is effective for Friedreich's Ataxia?

Research has shown that breathing exercises might aid individuals with Friedreich's Ataxia by enhancing muscle function. In this condition, coordination issues and muscle weakness can complicate breathing. Some studies suggest that exercises such as breathing training can improve muscle performance. However, there is not yet sufficient evidence to strongly recommend this treatment specifically for breathing issues in Friedreich's Ataxia. Early results show promise in boosting overall muscle strength and endurance. Participants in this trial will use a respiratory strength training device at home, which will be tested for its effectiveness in enhancing muscle strength and endurance. ^{1 2 3 6 7}

Who Is on the Research Team?

Carmen Leon Astudillo, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for individuals who can perform pulmonary function tests, have genetically confirmed Friedreich's Ataxia, and show a certain level of swallowing difficulty. It's not specified who cannot join the trial.

Inclusion Criteria

My genetic test confirmed I have Friedreich's Ataxia.

My swallowing test score is 1 or higher.

I can do lung function tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive respiratory strength training using a device at home up to 5 times a week for 12 weeks

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Respiratory Strength Training

Trial Overview The study examines the effects of Respiratory Strength Training (RST) on patients with Friedreich's Ataxia over 12 weeks. Participants will undergo evaluations including swallowing assessments, lung function tests, muscle activity measurements, and surveys before and after training.

How Is the Trial Designed?

Group I: Respiratory Strength Training (RST) Experimental Treatment 1 Intervention

Participants will receive a respiratory strength training device to take home and use up to 5 times a week for 12 weeks.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study of 11 patients with Friedreich's Ataxia (F.A.), the respiratory centers showed a heightened sensitivity to hypercapnia (increased carbon dioxide) compared to matched controls, indicating that these centers are functioning adequately.

However, the patients' responses to hypoxia (low oxygen) were similar to those of the controls, suggesting that the respiratory issues in F.A. patients do not stem from impaired respiratory center function, which helps clarify the causes of cardio-respiratory insufficiency in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of respiration in Friedreich's ataxia. Begin, R., Lupien, L., Bureau, MA., et al.[2019]

Respiratory muscle training (RMT) showed a tendency to improve expiratory muscle strength, vital capacity, and residual volume in individuals with spinal cord injury, based on a review of six controlled trials.

However, due to insufficient data and variability in outcomes, no definitive conclusions could be drawn regarding RMT's effects on inspiratory muscle strength, endurance, quality of life, exercise performance, or respiratory complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory muscle training in persons with spinal cord injury: a systematic review. Van Houtte, S., Vanlandewijck, Y., Gosselink, R.[2022]

A systematic review of 15 trials, including 6 randomized controlled trials, found that respiratory muscle training can lead to significant improvements in pulmonary function in patients with multiple sclerosis (MS), particularly in those with lower disability scores.

Training protocols typically lasted between 10 weeks to 3 months, involving daily sessions that improved maximum inspiratory and expiratory pressures, suggesting that targeted respiratory training could be beneficial for MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training of respiratory muscles in patients with multiple sclerosis: a systematic review. Martín-Valero, R., Zamora-Pascual, N., Armenta-Peinado, JA.[2018]

In a study comparing 16 individuals with Friedreich ataxia (FRDA) to 10 able-bodied controls, both groups showed similar mitochondrial capacity in their forearm muscles, indicating that mitochondrial function may not be impaired in FRDA.

However, individuals with FRDA exhibited significantly lower muscle endurance (19.2% less at 6 Hz) and reported 34% lower feelings of physical energy, suggesting that while mitochondrial capacity is preserved, muscle endurance and energy levels are negatively affected by the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial capacity, muscle endurance, and low energy in friedreich ataxia. Bossie, HM., Willingham, TB., Schoick, RAV., et al.[2022]

Respiratory muscle strength training (RMST) significantly improved inspiratory muscle strength by 73-74% and expiratory muscle strength by 31-48% in two patients with late-onset Pompe disease over a period of 12-32 weeks.

These results indicate that RMST can effectively enhance respiratory muscle strength even in patients with severe respiratory weakness who are undergoing long-term enzyme replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased inspiratory and expiratory muscle strength following respiratory muscle strength training (RMST) in two patients with late-onset Pompe disease. Jones, HN., Moss, T., Edwards, L., et al.[2011]

Respiratory muscle training has shown effectiveness in improving respiratory muscle strength, swallowing function, and phonation in patients with Parkinson's disease, based on a review of three randomized controlled trials involving 111 participants.

While the training led to significant improvements in measures like maximal inspiratory and expiratory pressure, the overall evidence is limited due to the small number of studies available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should respiratory muscle training be part of the treatment of Parkinson's disease? A systematic review of randomized controlled trials. Rodríguez, MÁ., Crespo, I., Del Valle, M., et al.[2022]

Respiratory muscle endurance training (RMET) significantly improved respiratory muscle function in spinal cord injury (SCI) athletes, particularly increasing maximal expiratory strength and respiratory endurance.

While RMET reduced the perception of dyspnoea during exercise, it only slightly enhanced overall exercise performance, indicating that while it benefits respiratory function, the impact on physical performance is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory muscle training in athletes with spinal cord injury. Vergès, S., Flore, P., Nantermoz, G., et al.[2009]

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]

Respiratory muscle training (RMT) significantly improved cough function in patients with neurological disorders, enhancing both voluntary and involuntary cough flow, as shown in a meta-analysis of five studies involving 185 participants.

While RMT showed positive effects on cough function, it did not demonstrate statistically significant improvements in inspiratory and expiratory muscle strength, indicating that further research is needed to clarify its overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of respiratory muscle training on cough function in neurological disorders: A systematic review with meta-analysis. He, Y., Zhao, C., Liu, Y.[2021]

In a study involving 122 stroke patients, those who underwent respiratory muscle training (RMT) showed significantly greater improvements in pulmonary function and respiratory muscle strength compared to those receiving standard rehabilitation after just four weeks.

The RMT group also experienced a lower incidence of respiratory complications, such as pneumonia, indicating that RMT may be an effective intervention to enhance recovery and reduce risks in acute stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Respiratory Muscle Training Improves Pulmonary Function and Respiratory Muscle Strength in Acute Stroke Patients. Choi, HE., Jo, GY., Do, HK., et al.[2021]

The upper limb cardiopulmonary exercise test (CPET) revealed that patients with Friedreich ataxia (FRDA) had a significant 31% reduction in peak oxygen uptake compared to healthy controls, indicating impaired exercise capacity.

The CPET is a valuable and safe tool for assessing exercise tolerance in FRDA patients, correlating with disease severity and potentially serving as an effective endpoint in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of upper limb cardiopulmonary exercise test in Friedreich ataxia. Pane, C., Salzano, A., Trinchillo, A., et al.[2022]

In adults with Friedreich's ataxia (FRDA), there is a significantly prolonged decline in skeletal muscle oxidative metabolism after exercise, indicating decreased oxidative phosphorylation capacity compared to healthy adults (274 seconds vs. 138 seconds).

The study suggests that CrCEST MRI can serve as a valuable biomarker for assessing muscle-specific metabolic decline in FRDA, which may help track disease progression over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich's ataxia. Schur, GM., Dunn, J., Nguyen, S., et al.[2022]

Respiratory muscle training (RMT), including inspiratory muscle training (IMT) and expiratory muscle training (EMT), shows some evidence of improving respiratory function in patients with neurodegenerative disorders like Parkinson's disease and multiple sclerosis, based on a review of 10 studies.

However, the overall quality and quantity of the studies are insufficient to definitively conclude the effectiveness of RMT for these patients, as only six out of sixteen quality assessment criteria were met in the analyzed studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory muscle training for respiratory deficits in neurodegenerative disorders: a systematic review. Reyes, A., Ziman, M., Nosaka, K.[2018]

Respiratory muscle strength training (RMST) can be tailored to target specific muscle groups based on individual needs, such as improving inspiratory strength for those with neurogenic injuries or enhancing expiratory strength for voice users with laryngeal dysfunction.

Recent research on RMST has shown promising results in increasing expiratory muscle force in individuals with Parkinson's disease, addressing their challenges with breathing, swallowing, and cough production as the disease progresses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory strength training: concept and intervention outcomes. Sapienza, C., Troche, M., Pitts, T., et al.[2011]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06539598?cond=Friedreich's%20Ataxia&aggFilters=status:rec&rank=3

NCT06539598 | Respiratory Training in Friedreich's Ataxia This is a prospective interventional study of patients with Friedreich's Ataxia that receive respiratory strength training for a period of 12 weeks with two ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9497209/

Respiratory Function in Friedreich's Ataxia - PMC Our data support the prominent role of in-coordination and muscle weakness in modulating respiratory efficiency, with scoliosis weighting as a ...

3. frdaguidelines.org frdaguidelines.org/wp-content/uploads/2022/10/6.1-2.-Should-respiratory-strength-training-vs.-no-intervention-be-used-for-for-people-with-respiratory-we.pdf

Should respiratory strength training vs. no intervention be ... We cannot recommend either respiratory strength training or no respiratory strength training for people with Friedreich ataxia and respiratory weakness and ...

4. rarediseaseadvisor.com rarediseaseadvisor.com/news/trial-sets-out-to-evaluate-the-effect-of-respiratory-training-in-fa/

Trial Sets Out to Evaluate the Effect of Respiratory Training ... A clinical trial that is testing the effect of respiratory training in swallowing and respiratory function in patients with FA is now open.

5. mdpi.com mdpi.com/2813-0413/4/1/1

Muscle Endurance Training in a Person with Friedreich's ... Taken together, these studies suggest that exercise training can improve muscle function in people with FRDA. mVO2max was 5% greater after NMES training.

6. mdpi.com mdpi.com/2227-9067/9/9/1319

Respiratory Function in Friedreich's Ataxia Our study aims to make an objective analysis of the respiratory condition of both early and late stage FRDA patients, looking for correlations with the motor, ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603753/

Respiratory Muscle Strength Training - StatPearls - NCBI Respiratory muscle strength training (RMST) comprises exercises and techniques designed to enhance the strength and endurance of respiratory muscles.