Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06630650
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-06
Brief Title:
A Prospective Natural History and Outcome Measure Validation Study of Congenital Myasthenic Syndromes
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Single Center Prospective Natural History and Outcome Measure Validation Study of Congenital Myasthenic Syndromes
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Congenital myasthenic syndromes CMSs are a group of inherited disorders that affect how the nerves communicate with muscles These can cause many problems that affect how people can move and use their bodies
Objective
This is a natural history study to learn more about how CMSs affect the body and cause changes over time
Eligibility
People aged 6 months or older with a CMS The study will focus on DOK7- and COLQ-related CMSs as well as other forms
Design
Participants will have up to 7 visits in 5 years At each visit participants will undergo many tests including
Physical exam with blood and urine tests
Tests of their heart and lung function
Exams of the eyes lungs muscles and nerves These will be done with different specialists
Exams of the arms and hands and of body use and movements These will also be done with specialists
Photos and videos may be taken
Muscle ultrasound Participants will lie still as a wand is rubbed over their skin
Magnetic resonance imaging MRI scans Participants will lie still on a bed that slides partway into a large tube A parent or other person may remain in the room too The scan will take 60 minutes
Electromyography EMG Participants will lie still or may be asked to move around A machine will measure the electrical activity in their muscles
An activity monitor may be placed on the participant s wrist ankle or hip for up to 2 weeks The monitor is about the size of a wristwatch
A sample of skin may be removed
Congenital myasthenic syndromes CMSs are a group of inherited disorders that affect how the nerves communicate with muscles These can cause many problems that affect how people can move and use their bodies
Objective
This is a natural history study to learn more about how CMSs affect the body and cause changes over time
Eligibility
People aged 6 months or older with a CMS The study will focus on DOK7- and COLQ-related CMSs as well as other forms
Design
Participants will have up to 7 visits in 5 years At each visit participants will undergo many tests including
Physical exam with blood and urine tests
Tests of their heart and lung function
Exams of the eyes lungs muscles and nerves These will be done with different specialists
Exams of the arms and hands and of body use and movements These will also be done with specialists
Photos and videos may be taken
Muscle ultrasound Participants will lie still as a wand is rubbed over their skin
Magnetic resonance imaging MRI scans Participants will lie still on a bed that slides partway into a large tube A parent or other person may remain in the room too The scan will take 60 minutes
Electromyography EMG Participants will lie still or may be asked to move around A machine will measure the electrical activity in their muscles
An activity monitor may be placed on the participant s wrist ankle or hip for up to 2 weeks The monitor is about the size of a wristwatch
A sample of skin may be removed
Detailed Description:
Study Description
This natural history and outcome measure validation study aims to longitudinally characterize the clinical manifestations of all congenital myasthenic syndromes CMS with a focus on DOK7 and COLQ-related CMS Both are ultra-rare inherited disorders of the neuromuscular junction This study will also assess the validity and test-retest reliability of outcome measures to support clinical trial readiness in these populations
Primary Objective
Characterize baseline clinical manifestations and CMS disease course over one year
Co-Primary Objective
Assess the validity and test-retest reliability of outcome measures in CMS
Secondary Objectives
Characterize the extended disease course of CMS Years 2 through 5
Exploratory Objectives
Biomarker identification accelerometer validation and MCID estimation
Primary Endpoints
Change from baseline to Year 1 in the following as age-appropriate and tolerated-performed in all participants unless age ranges specified
Physical strength
MRC scale all as tolerateddevelopmentally appropriate
Quantitative muscle assessment of shoulder abductors elbow flexorsextensors hip flexors and knee extensorsflexors QMA 7y
Myotools grip and pinch strength 6y
Physical performance
Six-minute walk test distance 6y
Repeated 1 minute sit to stand 2y
Performance of Upper Limb PUL 2y
Time of outstretched arm 2y
Disease severity
--Quantitative Myasthenia Gravis QMG Score 12y
Motor function 2y
Hammersmith infant neurological scale score 2y
Sitting balance score 2y
Motor function 2y
Motor function measure score MFM20 2-6y MFM32 7y
Time to ascend four stairs descend four stairs supine to stand 5y
Development
--Developmental motor scale quotients 5y
Pulmonary function 5y
Forced vital capacity FVC
Slow vital capacity SVC
Forced vital capacity at 1 second FEV1
Maximum inspiratory and expiratory pressures MIPMEP
End-tidal CO2 ETCO2
Quality of life
Myasthenia Quality of Life PM-QOL15 18y MG-QOL15 18
PROMIS-57 Profile 18y
PROMIS Ped-25 Profile 8-17y
PROMIS Parent Proxy CAT 5-7y
NeuroQoL fatigue and upper and lower limb function domains 8y
MG-ADL 18y
Serious adverse and disease-related events
Narrative clinician description
Causality assessment related or unrelated to the research or disease
Event severity CTCAE v5
Event MedDRA system organ class and preferred term
Co-Primary Endpoints
Test-retest reliability in physical strength physical performance motor function and quality of life primary endpoints
Secondary Endpoints
Change over time in primary endpoints Years 2 through 5
Exploratory Endpoints
Physical performance
Timed up and go TUG test x3 2y
Wearable sensor metrics during physical performance tests
Biomechanics
Stride length cadence velocity captured in clinic by wearable device
Stride velocity 95th centile
Free-living physical activity
Endpoints collected over 2-week data capture period will include
Number of sit-to-stand transitions
Step count
Average cadence per walking episode
Number of falls
Activity counts light moderate vigorous moderate to vigorous
Upper limb movements
Proposal to use in infantstoddlers use of one devicechest strap
Ophthalmology
Marginal reflex distance Ptosis
Binocular horizontal visual field test
Pupillometry
Goldmann Perimetry Degrees lateral rectus superior rectus inferior oblique medial rectus superior oblique inferior rectus
Quality of life
CMS-ST- InfantYoung Child 6 months - 3 years of age
CMS-ST ChildAdult 4 years - 18 years
Biomarkers
Peripheral biomarkers
Optional skin punch biopsy fibroblast culture
Imaging
Muscle MRI lower extremities T1 and Dixon
Muscle ultrasound echogenicity
Nerve function
--EMGNCS sfEMG and RNS
Measurement of AE burden
Adverse Event Unit AEU
This natural history and outcome measure validation study aims to longitudinally characterize the clinical manifestations of all congenital myasthenic syndromes CMS with a focus on DOK7 and COLQ-related CMS Both are ultra-rare inherited disorders of the neuromuscular junction This study will also assess the validity and test-retest reliability of outcome measures to support clinical trial readiness in these populations
Primary Objective
Characterize baseline clinical manifestations and CMS disease course over one year
Co-Primary Objective
Assess the validity and test-retest reliability of outcome measures in CMS
Secondary Objectives
Characterize the extended disease course of CMS Years 2 through 5
Exploratory Objectives
Biomarker identification accelerometer validation and MCID estimation
Primary Endpoints
Change from baseline to Year 1 in the following as age-appropriate and tolerated-performed in all participants unless age ranges specified
Physical strength
MRC scale all as tolerateddevelopmentally appropriate
Quantitative muscle assessment of shoulder abductors elbow flexorsextensors hip flexors and knee extensorsflexors QMA 7y
Myotools grip and pinch strength 6y
Physical performance
Six-minute walk test distance 6y
Repeated 1 minute sit to stand 2y
Performance of Upper Limb PUL 2y
Time of outstretched arm 2y
Disease severity
--Quantitative Myasthenia Gravis QMG Score 12y
Motor function 2y
Hammersmith infant neurological scale score 2y
Sitting balance score 2y
Motor function 2y
Motor function measure score MFM20 2-6y MFM32 7y
Time to ascend four stairs descend four stairs supine to stand 5y
Development
--Developmental motor scale quotients 5y
Pulmonary function 5y
Forced vital capacity FVC
Slow vital capacity SVC
Forced vital capacity at 1 second FEV1
Maximum inspiratory and expiratory pressures MIPMEP
End-tidal CO2 ETCO2
Quality of life
Myasthenia Quality of Life PM-QOL15 18y MG-QOL15 18
PROMIS-57 Profile 18y
PROMIS Ped-25 Profile 8-17y
PROMIS Parent Proxy CAT 5-7y
NeuroQoL fatigue and upper and lower limb function domains 8y
MG-ADL 18y
Serious adverse and disease-related events
Narrative clinician description
Causality assessment related or unrelated to the research or disease
Event severity CTCAE v5
Event MedDRA system organ class and preferred term
Co-Primary Endpoints
Test-retest reliability in physical strength physical performance motor function and quality of life primary endpoints
Secondary Endpoints
Change over time in primary endpoints Years 2 through 5
Exploratory Endpoints
Physical performance
Timed up and go TUG test x3 2y
Wearable sensor metrics during physical performance tests
Biomechanics
Stride length cadence velocity captured in clinic by wearable device
Stride velocity 95th centile
Free-living physical activity
Endpoints collected over 2-week data capture period will include
Number of sit-to-stand transitions
Step count
Average cadence per walking episode
Number of falls
Activity counts light moderate vigorous moderate to vigorous
Upper limb movements
Proposal to use in infantstoddlers use of one devicechest strap
Ophthalmology
Marginal reflex distance Ptosis
Binocular horizontal visual field test
Pupillometry
Goldmann Perimetry Degrees lateral rectus superior rectus inferior oblique medial rectus superior oblique inferior rectus
Quality of life
CMS-ST- InfantYoung Child 6 months - 3 years of age
CMS-ST ChildAdult 4 years - 18 years
Biomarkers
Peripheral biomarkers
Optional skin punch biopsy fibroblast culture
Imaging
Muscle MRI lower extremities T1 and Dixon
Muscle ultrasound echogenicity
Nerve function
--EMGNCS sfEMG and RNS
Measurement of AE burden
Adverse Event Unit AEU
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None