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: Unknown

8 Participants Needed

Trial Summary

What is the purpose of this trial?

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 research visits at the beginning and at the end of the study period. Visits include swallowing evaluation with fiberoptic endoscopic evaluation of swallowing, pulmonary function testing, surface electromyography and patient surveys.

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 data supports the idea that Respiratory Training for Friedreich's Ataxia is an effective treatment?

The available research shows that Respiratory Training, also known as Respiratory Muscle Training, can improve the strength of breathing muscles in people with neurological disorders. For example, in patients with late-onset Pompe disease, a similar condition, this training increased the strength of muscles used for breathing by up to 74%. Although the research does not specifically mention Friedreich's Ataxia, these findings suggest that similar improvements might be possible for people with this condition. However, the effectiveness of this treatment for Friedreich's Ataxia specifically is not clearly established in the available research. ^{1 2 3 4 5}

What safety data exists for respiratory muscle training?

The available research on respiratory muscle training (RMT) primarily focuses on its effectiveness rather than safety. Studies have shown improvements in respiratory muscle strength and pulmonary function in various conditions, such as spinal cord injury and neurological disorders. However, specific safety data is limited, and the effects on inspiratory muscle strength, respiratory muscle endurance, quality of life, exercise performance, and respiratory complications remain inconclusive. No significant adverse effects have been reported in the studies reviewed, but comprehensive safety evaluations are lacking. ^{1 6 7 8 9}

Is Respiratory Strength Training a promising treatment for Friedreich's Ataxia?

Yes, Respiratory Strength Training is promising for Friedreich's Ataxia because it can help improve breathing and heart function, which are often affected by the disease. This type of training can enhance the body's ability to use oxygen and increase endurance, potentially leading to better overall health and quality of life for patients. ^{10 11 12 13 14}

Research Team

Carmen Leon Astudillo, MD

Principal Investigator

University of Florida

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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 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]

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 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]

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]

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 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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of respiratory muscle training on cough function in neurological disorders: A systematic review with meta-analysis. [2021]

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

Respiratory muscle training for respiratory deficits in neurodegenerative disorders: a systematic review. [2018]

3. United States 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. [2011]

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

Respiratory strength training: concept and intervention outcomes. [2011]

5. England 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. [2022]

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

Respiratory muscle training in persons with spinal cord injury: a systematic review. [2022]

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

Comprehensive Respiratory Muscle Training Improves Pulmonary Function and Respiratory Muscle Strength in Acute Stroke Patients. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Respiratory muscle training in athletes with spinal cord injury. [2009]

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

Training of respiratory muscles in patients with multiple sclerosis: a systematic review. [2018]

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

Endurance exercise training in Friedreich ataxia. [2006]

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

Mitochondrial capacity, muscle endurance, and low energy in friedreich ataxia. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Regulation of respiration in Friedreich's ataxia. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Safety and feasibility of upper limb cardiopulmonary exercise test in Friedreich ataxia. [2022]

14. Germany pubmed.ncbi.nlm.nih.gov

In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich's ataxia. [2022]