Primary Objective:1) To determine the efficacy of personalized progressive resistance training (PRT) on muscle strength of elbow flexors in children and adolescents with Spinal Muscular Atrophy and Congenital Myopathy compared to usual care…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective 1 (primary outcome measure):
The change in maximal isometric strength of the elbow flexors (Newton) after 14
weeks progressive resistance training
Secondary outcome
Objective 2 (progressive resistance training + DMT versus usual care + DMT for
SMA, progressive resistance training versus usual care for CM):
The change in maximal isometric strength of the elbow flexors (Newton) after 14
weeks progressive resistance training
Objective 3 (muscle profile):
At baseline functional, electrophysiological, morphological and metabolic
parameters will be assessed on the basis of which an individual muscle profile
is composed:
Function (Isokinetic Dynamometry)
• Isometric muscle strength (Newton, Newton/cm2) of the elbow flexors and elbow
extensors
• Muscle power (watts) defined as average power during 5 isokinetic
contractions of the elbow flexors and extensors
• Muscle endurance (seconds) measured with the dynamic IMPACT ergometer
Electrophysiological (High Density surface EMG)
• HD-EMG: root mean sqsuare (RMS) normalized to muscle activity during maximal
isometric contraction, power spectrum analysis (e.g. median frequency (MF)),
muscle fiber conduction velocity (MFCV), motor unit characteristics derived
after decomposition (e.g. recruitment patterns, motor unit size, conduction
velocity, etc.) 29-33. In addition, time until failure during the 60% of the
maximal torque test will be measured.
Metabolic (Magnetic Resonance Spectroscopy)
• high-energy phosphate metabolites including ATP, PCr, Pi, and myofiber pH
measured during (A) rest, (B) exercise, and (C) post-exercise.
Morphological (Magnetic Resonance Imaging)
• Muscle MRI: muscle fat fraction, muscle volume, contractile cross-sectional
area (cCSA), muscle inflammation, and tissue architecture.
Objective 4 (clinical relevance)
• Goal Attainment Scaling (GAS) (score) on 1-3 personal goals
• Revised Upper Limb Score (total score)
• PROMIS global 02(R1)
• PROMIS fatigue SF (total score)
• PROMIS Upper Extremity SF (total score)
• Pittsburg Sleep Quality Index (total score)
Background summary
Progressive resistance (muscle strength- and muscle power-) training (PRST) is
increasingly recommended in health care standards to combat disease progression
in muscle disease. However, due to the lack of evidence on the efficacy of PRT,
these recommendations remain vague and are therefore not easily translated into
specific treatment of various muscle diseases.
Study objective
Primary Objective:
1) To determine the efficacy of personalized progressive resistance training
(PRT) on muscle strength of elbow flexors in children and adolescents with
Spinal Muscular Atrophy and Congenital Myopathy compared to usual care
Secondary Objective(s):
2) To determine the efficacy of personalized PRT on muscle strength of elbow
flexors in children and adolescents combined with DMT compared to DMT alone as
usual care, in patients with SMA.
To determine the efficacy of personalized PRT on muscle strength of elbow
flexors in children and adolescents with CM compared to usual care.
3) To determine the efficacy of personalized PRT on muscle strength of elbow
flexors in children and adolescents with a *red muscle* compared to a *white
muscle* profile.
4) To determine the clinical relevant effect of personalized PRT on muscle
strength of elbow flexors in children and adolescents with Spinal Muscular
Atrophy and Congenital Myopathy compared to usual care.
Study design
Multicenter randomized controlled double-blinded trial.
Intervention
14-week, 3 times weekly supervised progressive resistance training. The
training program will be personalized with respect to training load and
exercises, guided by individual treatment goals.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit, and group relatedness:
The training group (controlled period: week 3-16) and the control group
(follow-up period: week 17-31) will both receive a progressive resistance
training program of arm and shoulder muscles (30-45 minutes, 3 times a week,14
weeks) during this study. To reduce the burden of traveling, training sessions
will be performed at home or at their local physical therapy practice. All
training sessions will be physically supervised and closely monitored,
affording further tailoring of the training program when needed. Participants
will visit UMCU three times, AMC or UMCU one time (with a second visit optional
to reduce total burden), and will be visited once at home over a time period of
31 weeks. The three mandatory UMCU hospital visits (Spieren voor Spieren
Inspanningslab) for functional and electrophysiological muscular evaluation
will take 2-3 hours (note: standard care for these patients is one or two
annual sessions of 2-3 hrs for multidisciplinary examination featuring similar
assessmments of motor function, muscle strength and questionnaires). The
mandatory single visit to AMC Hospital or UMCU hospital (Department of
Radiology and Nuclear Medicine) for Magnetic Resonance metabolic and
morphological muscular assessment will take 90 min. Patients will be screened
for contra-indications before undergoing MR examination. A optional second
visit after 14 weeks will inform on any muscular metabolic and morphological
treatment response. All functional (strength), electrophysiological (EMG),
morphological (MRI and metabolic (MRS) measurements are feasible and have
negligible risks. They have been frequently used and are well tolerated in
usual care and (ongoing) research performed in our Center with METC approval
(METC-nr: 14-230/NL48715.041.14, 14-536/NL38048.041.14, 09-307). The risk of
strength training is negligible. Spinal Musclar Atrophy and Congenital
Myopathy have no increased risk of exercise-induced muscle damage and recent
studies report no adverse events. Patients will be closely monitored and
training intensity will be adapted when necessary. The criteria of the
Nederlandse Vereniging voor Kindergeneeskunde (Dutch Association of
Paediatrics) concerning research involving children will be strictly applied.
Subjects may experience direct benefits from participating in this study in the
form of a clinical relevant improvement in muscle function. Clinicians will
gain more insight into the effects and working mechanism of personalized PRST,
the importance of combinatory treatement and which individual muscle profiles
may benefit most from PRST. This will help them to optimize and personalize
training programs exercise for their patients and provide patients with a new
treatment option to improve daily life activities, leisure activities, and
sports participation. *
Lundlaan 6
Utrecht 3594CX
NL
Lundlaan 6
Utrecht 3594CX
NL
Listed location countries
Age
Inclusion criteria
• Genetically confirmed diagnosis of SMA5q or CM27
• Age 10 to 30 years old.
• Ability to execute a biceps-curl with at least 1 kg
Exclusion criteria
• Insufficient understanding of the Dutch language.
• Inability to meet study visits
• Experimental treatment that may alter muscle function (eg myostatin
inhibitors)
• Considering adjusting the dose of medication during the study that might
affect the motor unit function (e.g. pyridostigmine, salbutamol)
• Risk factors for exercise testing registered by a Dutch version of the
preparticipation Questionnaire (American College of Sports Medicine and
American Heart Association). Possible risk factors will be discussed with a
medical exercise physiologist and neurologist before a subject can be
included.
• Medical disorders i.e. comorbidities or being under examination, that
prohibit progressive resistance training or could influence the intervention
outcome.
• Surgery affecting training ability < 3-6 months prior to the start of the
program, depending on the type of surgical intervention (e.g. scoliosis
correction).
• Pregnancy or current wish to become pregnant.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85860.041.24 |