Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)

Study Overview
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Brief Summary
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Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is one of the most common inherited neurological disorders. The study will evaluate the efficacy and safety of an innovative rehabilitation protocol constituted by exercises at the treadmill and by a stretching and proprioceptive approach. A total of 92 patients will be enrolled in the study and treated in a controlled, randomized, single blind, way. To recruit a high number of patients with CMT1A the study will be multicentric and will comprehend four of the most active clinical centers in the field of CMT, in Italy. People with CMT1A are very motivated in entering rehabilitation protocols because to date there is no effective therapy for this disease. Therefore, the investigators expect a high compliance by the patients. With the present project the investigators plan to clarify several unanswered questions: 1) the efficacy and safety of treadmill over a more conventional protocol; 2) the duration and frequency of any rehabilitation treatment; 3) the most sensitive outcome measures to evaluate the efficacy of rehabilitation approach in patients with CMT.

Detailed Description
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A multicentre, prospective, randomised, controlled, single blind study to evaluate the impact of aerobic exercise, based on a tightly controlled program at the treadmill, on the rehabilitation therapy of CMT 1A neuropathy. Comparing aerobic training at the treadmill combined with respiratory physiotherapy, stretching and proprioceptive exercises (TreSPE- treated group) with a more conventional treatment only composed by respiratory physiotherapy, stretching and proprioceptive exercises (SPE- control group) will provide information on the impact of Treadmill in CMT1A. 92 patients (23 per centre) will be enrolled and randomly assigned to TreSPE (n = 46) or to SPE (n = 46). Both groups will be treated for three months and followed up for six months. No serious side effects are expected with TreSPE, as also suggested by our preliminary results. For safety reasons blood pressure (BP), heart rate (HR) and an electrocardiogram will be recorded during the rehabilitation treatment when the treating physician considers it necessary. The patients will be allowed, if needed, to hold at the parallel bars of the treadmill during exercise. According to the American Thoracic Society (ATS) guidelines the cardiopulmonary exercise test will be interrupted if BP raises at 240/120 and/or HR to 220-patients age.

Official Title
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A Multicenter Study to Evaluate the Effects on Charcot-Marie-Tooth Neuropathy Type 1A of a Composite Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program.

Conditions
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Charcot-Marie-Tooth Disease, Charcot-Marie-Tooth Disease Type 1A

Intervention / Treatment
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* Other: TreSPE
* Other: SPE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of CMT1A Genetic confirmation (17p112 chromosome duplication) Age 18 - 70 years old Ability to accomplish the primary outcome measure (10 meter walking test) without support, with or without ankle foot orthoses (AFO) Ability to walk on a treadmill on a horizontal plane for 20 minutes at a speed of 1.5 km/h with or without support at the bars Score at the Mobility Scale between 2 and 11 Signed written informed consent to participate Exclusion Criteria: Diagnosis of Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) or any other type of CMT Other associated causes of neuropathy Vestibular affections, psychiatric, cardiovascular and lung disorders or severe arthropathic changes in the lower limbs Non ambulating patients or patients always requiring even monolateral support to walk Other neurological disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TreSPE<br>Treatment with treadmill, proprioceptive and stretching exercises | Other: TreSPE<br>* treadmill: 5'warm up, 20'aerobic exercise (gradually incremented to 30', from session to session, if possible), 5'warm down, controlling hearth rate, blood pressure and SaO2. Respiratory Physiotherapy: positive Expiratory Pressure (PEP) bottle for 10' (in various postures), and postural training, for the other 10'. Stretching for 20', of the triceps surae, tibialis posterior, extensor and flexors digitorum longus and brevis, both at the bed and in a static position. Proprioceptive and postural kinesitherapy according to the Perfetti method. Balance Exercising consists of exercises carried on by basculating bars with improving difficulties in the instruments utilized and in the tasks with therapist supervision and near a handbar preventing falls.<br>* Other names: SPE;|
| Active Comparator: SPE<br>Proprioceptive and stretching exercises | Other: TreSPE<br>* treadmill: 5'warm up, 20'aerobic exercise (gradually incremented to 30', from session to session, if possible), 5'warm down, controlling hearth rate, blood pressure and SaO2. Respiratory Physiotherapy: positive Expiratory Pressure (PEP) bottle for 10' (in various postures), and postural training, for the other 10'. Stretching for 20', of the triceps surae, tibialis posterior, extensor and flexors digitorum longus and brevis, both at the bed and in a static position. Proprioceptive and postural kinesitherapy according to the Perfetti method. Balance Exercising consists of exercises carried on by basculating bars with improving difficulties in the instruments utilized and in the tasks with therapist supervision and near a handbar preventing falls.<br>* Other names: SPE;Other: SPE<br>* Respiratory Physiotherapy for 20', consisting of Positive Expiratory Pressure (PEP) bottle for 10' (in various postures), and postural training according to the Mèzières technique, for the other 10'. Stretching for 20', of the triceps surae, tibialis posterior, extensor and flexors longus and brevis, both at the bed and in a static position. Proprioceptive and postural kinesitherapy according to the neurocognitive method. Balance Exercising consists of exercises carried on by moving bars with improving difficulties in the instruments utilized and in the tasks with therapist supervision and near a handlebar preventing falls.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking ability of patients will be evaluated as the time needed to walk for 10 meters at normal speed for the patients | The walking ability of patients will be evaluated through the 10 meters timed walk test which will be performed at baseline (T1 or day-1), at the end of the three months of treatment (T2 or day90) and at the end of the three months of follow up (T3 or day180). | Baseline: 1 day before the rehabilitative protocol starts (T1) | 
| Walking ability of patients will be evaluated after finishing the treatment as the time needed to walk for 10 meters at normal speed for the patients | The walking ability of patients will be evaluated through the 10 meters timed walk test which will be performed at baseline (T1 or day-1), at the end of the three months of treatment (T2 or day90) and at the end of the three months of follow up (T3 or day180). | at the end of treatment: day 90 (T2) | 
| Walking ability of patients will be evaluated after finishing the treatment as the time needed to walk for 10 meters at normal speed for the patients | The walking ability of patients will be evaluated through the 10 meters timed walk test which will be performed at baseline (T1 or day-1), at the end of the three months of treatment (T2 or day90) and at the end of the three months of follow up (T3 or day180). | at the end of follow up: day 180 (T3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Balance will be evaluated through the Berg Scale | The Berg scale is a tool to evaluate balance and ranges from 0 to 36 points being 36 normal | Baseline: 1 day before the rehabilitative protocol starts | 
| Balance will be evaluated through the Berg Scale | The Berg scale is a tool to evaluate balance and ranges from 0 to 36 points being 36 normal | at the end of treatment: day 90 (T2) | 
| balance will be evaluted through the Berg scale | The Berg scale is a tool to evaluate balance and ranges from 0 to 36 points being 36 normal | at the end of follow up: day 180 (T3) | 
| Quality of life will be evaluated through the SF - 36 questionnaire | The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. | Baseline: 1 day before the rehabilitative protocol starts (T1) | 
| Quality of life will be evaluated through the SF - 36 questionnaire | The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. | at the end of treatment: day 90 (T2) | 
| Quality of life will be evaluated through the SF - 36 questionnaire | The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. | at the end of follow up: day 180 (T3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Charcot-Marie-Tooth disease,, CMT1A,, rehabilitation,, treadmill,, stretching,, proprioception,, Randomised Controlled Trial.