Clinical trial NCT05544994: The Effect of Aerobic Exercise Training in Patients With Type III Spinal Muscular Atrophy
Official title: The Effect of Aerobic Exercise Training in Patients With Type III Spinal Muscular Atrophy"
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neuromuscular Diseases
Spinal Muscular Atrophy Type 3
Keywords: Spinal Muscular Atrophy Type 3
Aerobic Training
SMN protein level
Physiotherapy
Lead sponsor: Istanbul Medipol University Hospital
Sponsor class: OTHER
Collaborators: name: Istanbul University
First posted: 2022-09-19
Enrollment: 20
Sex: ALL
Minimum age (years): 10
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In the last 10-15 years, a better understanding of the pathophysiology and molecular genetics of SMA has led to the emergence of previously unavailable pharmacological and genetic treatments.One of these new treatments, Nusinersen, targets SMN2, which is a slightly different copy of SMN1, and increases SMN protein levels.

Preclinical studies have provided evidence that neuroprotection is strongly formed, with exercise significantly increasing motor neuron survival independent of SMN expression.

In a limited number of clinical studies prior to Nusinersen treatment, it was reported that aerobic exercise training improved maximum oxygen uptake (VO2 max) without causing muscle damage, but still caused fatigue.

The aim of this study is to determine the effect of aerobic exercise training on motor and respiratory functions, exercise capacity, fatigue and quality of life in SMA Type III patients who can walk and receive Nusinersen therapy. Twenty cases aged 10-50 years with genetically confirmed SMA diagnosis will be included in this study. The cases to be included in the study will be randomized into 2 groups as the training and control groups.

In addition to the routine physiotherapy program, medium-intensity Aerobic Exercise Training will be given to the study group for 12 weeks. Before and 12 weeks after the training, the cases will be evaluated with the Six Minute Walking Test, Submaximal Exercise Test, SMN protein level, function and strength assessments, (FVC) value, fatigue and quality of life scales.

In clinical trials, the supporting evidence for aerobic interventions in SMA is limited.

Additional studies on aerobic intervention parameters (frequency, intensity and duration) are needed.The results of this study will determine the feasibility of aerobic exercise training and provide important guidance for the clinical management of SMA patients.

Detailed description: Spinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord, leading to progressive muscle atrophy and weakness. Mutation or deletion of the survival motor neuron1 (SMN1) gene causes insufficient production of the SMN protein, which ensures motor neuron survival and maintenance in the spinal cord.

In the last 10-15 years, a better understanding of the pathophysiology and molecular genetics of SMA has led to the emergence of previously unavailable pharmacological and genetic treatments. One of these new treatments, Nusinersen targets SMN2, which is a slightly different copy of SMN1, increases SMN protein levels. Preclinical studies have provided evidence that exercise significantly increases motor neuron survival independent of SMN expression, and that neuroprotection is strongly formed. In a limited number of clinical studies prior to Nuinersen therapy, it was reported that aerobic exercise training improved maximum oxygen uptake (VO2 max) without causing muscle damage, but still caused fatigue and had no significant beneficial effect on physical functioning. This study aims to determine the effect of aerobic exercise training on motor and respiratory functions, exercise capacity, fatigue and quality of life in SMA Type III patients who can walk and receive Nusinersen treatment. Twenty patients between the ages of 10 and 50 with genetically confirmed SMA diagnosis will be included in this study. The patients will be randomly divided into 2 groups as the training and control groups. In addition to the routine physiotherapy program, the study group will be given a moderate-intensity Aerobic Exercise Training for 12 weeks. Before and after 12 weeks of training, subjects will be evaluated with the Six-Minute Walk Test, ,Submaximal Exercise Test, SMN protein level and function and strength assessments, (FVC) value, fatigue and quality of life scales.

In clinical trials, the supporting evidence for aerobic interventions in SMA is limited. It has been reported that SMA patients cannot tolerate excessive exercise intensity and that recovery may be prevented due to excessive fatigue. Additional studies on aerobic intervention parameters (frequency, intensity and duration) are needed. The results of this study will determine the feasibility of aerobic exercise training and will have an impact on clinical practice by providing important guidance to the clinical management of SMA patients.

Eligibility criteria: Inclusion Criteria:

* Have been diagnosed of SMA Type 3 confirmed by genetic analysis,
* Between the ages of 10-50,
* Being able to walk 25 m without assistive device

Exclusion criteria:

* Using research drugs for SMA treatment other than Nusinersen treatment,
* Having a serious systemic disease that may prevent exercise,
* Have had a lower extremity injury and/or surgery in the last 6 months,
* To be applying a regular aerobic training program in the last 6 months

Primary outcomes:
measure: Functional Capacity
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Submaximal Exercise Test
timeFrame: Baseline and 12 weeks
measure: Pulmonary Function
timeFrame: Baseline and 12 weeks
measure: Motor Function
timeFrame: Baseline and 12 weeks
measure: Motor Performance
timeFrame: Baseline and 12 weeks
measure: Balance and Mobility
timeFrame: Baseline and 12 weeks
measure: Muscle strength
timeFrame: Baseline and 12 weeks
measure: Quality of Life in patients with neuromuscular disease
timeFrame: Baseline and at 12 weeks
measure: Fatigue
timeFrame: Baseline and 12 weeks
measure: Functional Lower Extremity Strength,
timeFrame: Baseline and 12 weeks
measure: Evaluation of SMN protein levels in blood biochemistry
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istanbul Faculty of Medicine, Department of Neurological Sciences
state: Fatih
Study officials:
affiliation: Istanbul University, Istanbul Faculty of Medicine,Department of Neurological Sciences
name: Sezan Mergen KILIÇ, MSc PT
role: PRINCIPAL_INVESTIGATOR
affiliation: Medipol University, Health Sciences Faculty, Physiotherapy and Rehabilitation
name: Fatma Karantay Mutluay,, Professor
role: STUDY_DIRECTOR
affiliation: Istanbul University, Istanbul Faculty of Medicine,Department of Neurological Sciences
name: Fatma Yeşim Parman, Professor
role: STUDY_DIRECTOR
References: