Limb-Girdle Muscular Dystrophy Type 2I in Norway

Study Overview
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Brief Summary
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Key goals are to establish the natural history of limb-girdle muscular dystrophy type 2I (LGMD 2I) and identify feasible and sensitive tools and biomarkers to measure disease affection and progression, determine the Norwegian LGMD 2I prevalence, carrier frequency and genotypes, and to assess health-related quality of life in the Norwegian LGMD 2I population. Main aims are to facilitate future clinical trials and contribute to good clinical practice with suitable methodology and to complete health and social care in order to optimize the function and quality of daily living of the patient group.

Detailed Description
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A single-center study with Norwegian nationwide enrollment. Data is based on questionnaires, patient journals, clinical examination, a set of functional tests and biomarkers, and patient reported outcomes. Clinical/ paraclinical tests are repeated after 2-years in order to measure disease progression. Both skeletal muscle, heart and respiratory function will be examined. At baseline there will also be performed a sleep study in order to find if they are prone to sleep-disordered breathing.

Official Title
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Limb-Girdle Muscular Dystrophy Type 2I in Norway - a Cohort Study

Conditions
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Limb Girdle Muscular Dystrophy, Type 2I, Limb Girdle Muscular Dystrophy, Muscular Dystrophies, Limb Girdle Muscular Dystrophy R9 FKRP-related

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetical confirmed limb-girdle muscular dystrophy type 2I in Norway Live in Norway Written consent Exclusion Criteria: Children < 16 years are excluded from the assessment of quality of life and from the clinical/paraclinical part, but may contribute with information through questionnaires and patient journal. The study of prevalence and genotypes is anonymous and consent independent and will include everyone that is genetically LGMD 2I-confirmed in Norway.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echo intensity of muscles | Change in echo intensity at a defined cross-sectional level in muscles in limbs, musculus rectus abdominis and paraspinal muscles from baseline at 2 years. Echo intensity is measured as grayscale pixels ranging from 0 (black) to 255 (white) through histogram analysis by an ultrasound software program. It calculates the mean value from the superficial 1/3 of a manually selected region of interest in three consecutive images from same location. Increase in echo intensity indicates increase in pathology. | Baseline and 2 years | 
| Muscle thickness | Using ultrasound to measure changes in muscle thickness at a defined cross-sectional level in muscles in limbs, musculus rectus abdominis and paraspinal muscles from baseline at 2 years. | Baseline and 2 years | 
| Age at important disease stages | Document the variation in age of onset, age of loss of walking ability, age of established cardiac failure and age of established respiratory failure. | Retrospective data collection at baseline | 
| Rate of symptom progression | Document the variation in time from disease onset to loss of walking ability | Retrospective data collection at baseline | 
| Prevalence of recognized cardiomyopathy | The percentage of females and males with recognized cardiomyopathy | Retrospective data collection at baseline | 
| Prevalence of initiated ventilation support | The percentage of female and males that have initiated ventilation support. | Retrospective data collection at baseline | 
| Motor task performance | Using the standardised scoring instrument Motor Function Measure for neuromuscular diseases (MFM) to measure the ability to perform 32 different motor tasks. The individual item score ranges from 0 (cannot initiate the task) to 3 (performs fully and normally). The items are divided into 3 domains: 1) Standing and transfers (13 tasks), 2) Axial and proximal motor function (12 tasks), 3) Distal motor function (7 tasks). The 3 domains give rise to 3 subscores. Both subscores and total score (0-96 points) will be measured. Baseline and changes from baseline at two years. | Baseline and 2 years | 
| Disease-specific health-related quality of life (HRQOL) | Using the Individualized Neuromuscular Quality of Life (INQOL)-questionnaire to measure the burden of disease. It consists of 45 items. Each item is graded by a 7-point Likert scale (0-6/1-7).The 45 items make up 3 dimensions/domains: muscular symptoms, effects on life-domains (activities, independence, emotions, body image, social relationships) and effects of treatment. The 3 domains are together subdivided into 11 subdimensions, each with its own subscale. In addition there is a QOL-score which is a composite score from the Life-domain. The scores range from 0-100 and are determined by the item responses and a weighting algorithm. The higher the scores, the more negative impact. Both subscales and QOL-score will be determined - at baseline and changes from baseline at 6 months, 1 year and 2 years. | Baseline, at 6 months, 1 year | 
| Echocardiography strain speckle-tracking | Measure cardiac function at baseline and changes from baseline at 2 years | Baseline and 2 years | 
| Nocturnal arterial carbon dioxide (CO2)-level | Monitor transcutaneous CO2 during sleep at baseline. | Baseline | 
| MRI | Muscle MRI lower limbs | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Test (6MWT) | Walk distance in 6 minutes, Borgs scale for dyspnoea and fatigue pre and post test, and for self-reported exertion. Changes from baseline in 6MWT at 2 years | Baseline (2 tests with 1 day interval) and two years (2 tests with 1 day interval) | 
| 4-step stair climb test | Changes from baseline in time to ascend and to descend a 4-steps stair at two years | Baseline and 2 years | 
| Level of motor independence: Vignos Grade | Using Vignos grade to score level of motor independence. The score ranges from 1 (walk and climb without assistance) to 10 (confined to bed). | Baseline and 2 years | 
| Upper limb movement ability: Brooks Grade | Using Brooks Grade to score the ability to raise arms above the head, ranging from 1 (normal: full abduction until the hands touch above the head) to 6 (cannot raise hands to mouth and has no useful function of hands). Baseline and changes from baseline at two years. | Baseline and 2 years | 
| Hand held dynamometry | Changes from baseline in muscular strength in the limbs at two years | Baseline and 2 years | 
| Manual Muscular Testing (MMT) | Changes from baseline in muscular strength in the limbs at two years | Baseline and 2 years | 
| General health-related quality of life | Using the Norwegian translation of general HRQOL-instrument Short Form Health Survey (SF-36). It is a questionnaire with 36 questions (items) investigating 8 domains/dimensions (physical function, physical role limitations, emotional role limitations, social functioning, bodily pain, general health perceptions, vitality, mental health). The 8 domain scores will be determined. The scores range from 0-100 and are based on item-responses and weighting algorithm. High score stands for good health. Measure at baseline and changes from baseline at 6 months, 1 year and 2 years. | Baseline, 6 months, 1 year | 
| Plethysmography | Lung volumes at baseline, and changes from baseline at two years. | Baseline and 2 years | 
| Mean Inspiratory and Expiratory Pressure (MIP/MEP) | Static respiratory pressures at baseline, and changes from baseline at two years | Baseline and 2 years | 
| Forced Vital Capacity (FVC) | Dynamic spirometry while sitting, and supine when normal sitting. Baseline and changes from baseline at 2 years | Baseline and 2 years | 
| Diaphragm thickness ratio | Using ultrasound to measure thickness of diaphragm at maximum inspiration and at end-expiration. Ratio < 1,2 indicates reduced diaphragm movement. Bott left and right side will be measured. | Baseline and 2 years | 
| Nocturnal oxygen saturation | Monitor transcutaneous oxygen saturation during sleep. | Baseline and 2 years | 
| Cough Peak Flow | Cough Peak Flow at baseline and changes from baseline at 2 years | Baseline and 2 years | 
| Apnea-hypopnea index | Using polysomnography to calculate the number of obstructive and non-obstructive apnea and hypopnea events pr hour sleep. | Baseline | 
| Respiratory disturbance index | Using polysomnography to calculate the number of respiratory events in terms of apneas, hypopneas and respiratory effort-related arousals pr hour sleep. | Baseline | 
| Thoracoabdominal breathing pattern during sleep | Using polysomnography to detect paradoxal breathing movements during sleep (abdomen moving in on inspiration when supine). | Baseline | 
| Echocardiography - conventional | Measure cardiac function at baseline and changes from baseline at 2 years | Baseline and 2 years | 
| Electrocardiography (ECG) | Assessment of cardiac electrical activity at baseline and changes from baseline at 2 years | Baseline and 2 years | 
| Pain (visual analogous scale, VAS) | Patient-reported pain on VAS at baseline and at 2 years | Baseline and 2 years | 
| Fatigue (Visual Analogous Scale, VAS) | Patient-reported fatigue on VAS tat baseline and at 2 years | Baseline and 2 years | 
| Fatigue Severity Scale (FSS) | Fatigue at baseline and at 2 years | Baseline and 2 years | 
| Epworth Sleepiness Scale (ESS) | Assessment of daytime sleepiness at baseline | Baseline | 
| Capillary blood gas | Capillary CO2 at baseline and at 2 years | Baseline and 2 years | 
| Serum Creatine Kinase (s-CK) | s-CK at baseline and at 2 years | Baseline | 
| Insomnia | Using Bergen Insomnia Scale to measure insomnia. | Baseline | 
| Sleep quality | Using Pittsburgh Sleep Quality index to measure sleep quality | Baseline | 
| Cognitive status | Montreal Cognitive Assessment | Baseline |