Limb-Girdle Muscular Dystrophy Type 2I in Norway

Muscular Dystrophies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03930628
• Other study ID #: 2018/1968(REK)
• Status: Active, not recruiting
• Start date: January 6, 2020
• Est. completion date: June 2023

Study information

• Verified date: November 2022
• Source: University Hospital of North Norway
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 106
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Limb Girdle Muscular Dystrophy
• Limb Girdle Muscular Dystrophy, Type 2I
• Muscular Dystrophies

Locations

Country	Name	City	State
Norway	National Neuromuscular Centre, Norway	Tromsø

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital of North Norway	Norwegian Competence Center for Sleep Disorders, Norwegian Muscle Disease Association (FFM), Norwegian National Advisory Unit on Rare Disorders (NKSD), University of Tromso

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Rate of symptom progression	Document the variation in time from disease onset to loss of walking ability	Retrospective data collection at baseline
Primary	Prevalence of recognized cardiomyopathy	The percentage of females and males with recognized cardiomyopathy	Retrospective data collection at baseline
Primary	Prevalence of initiated ventilation support	The percentage of female and males that have initiated ventilation support.	Retrospective data collection at baseline
Primary	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
Primary	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
Primary	Echocardiography strain speckle-tracking	Measure cardiac function at baseline and changes from baseline at 2 years	Baseline and 2 years
Primary	Nocturnal arterial carbon dioxide (CO2)-level	Monitor transcutaneous CO2 during sleep at baseline.	Baseline
Primary	MRI	Muscle MRI lower limbs	At 2 years
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	Hand held dynamometry	Changes from baseline in muscular strength in the limbs at two years	Baseline and 2 years
Secondary	Manual Muscular Testing (MMT)	Changes from baseline in muscular strength in the limbs at two years	Baseline and 2 years
Secondary	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
Secondary	Plethysmography	Lung volumes at baseline, and changes from baseline at two years.	Baseline and 2 years
Secondary	Mean Inspiratory and Expiratory Pressure (MIP/MEP)	Static respiratory pressures at baseline, and changes from baseline at two years	Baseline and 2 years
Secondary	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
Secondary	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
Secondary	Nocturnal oxygen saturation	Monitor transcutaneous oxygen saturation during sleep.	Baseline and 2 years
Secondary	Cough Peak Flow	Cough Peak Flow at baseline and changes from baseline at 2 years	Baseline and 2 years
Secondary	Apnea-hypopnea index	Using polysomnography to calculate the number of obstructive and non-obstructive apnea and hypopnea events pr hour sleep.	Baseline
Secondary	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
Secondary	Thoracoabdominal breathing pattern during sleep	Using polysomnography to detect paradoxal breathing movements during sleep (abdomen moving in on inspiration when supine).	Baseline
Secondary	Echocardiography - conventional	Measure cardiac function at baseline and changes from baseline at 2 years	Baseline and 2 years
Secondary	Electrocardiography (ECG)	Assessment of cardiac electrical activity at baseline and changes from baseline at 2 years	Baseline and 2 years
Secondary	Pain (visual analogous scale, VAS)	Patient-reported pain on VAS at baseline and at 2 years	Baseline and 2 years
Secondary	Fatigue (Visual Analogous Scale, VAS)	Patient-reported fatigue on VAS tat baseline and at 2 years	Baseline and 2 years
Secondary	Fatigue Severity Scale (FSS)	Fatigue at baseline and at 2 years	Baseline and 2 years
Secondary	Epworth Sleepiness Scale (ESS)	Assessment of daytime sleepiness at baseline	Baseline
Secondary	Capillary blood gas	Capillary CO2 at baseline and at 2 years	Baseline and 2 years
Secondary	Serum Creatine Kinase (s-CK)	s-CK at baseline and at 2 years	Baseline
Secondary	Insomnia	Using Bergen Insomnia Scale to measure insomnia.	Baseline
Secondary	Sleep quality	Using Pittsburgh Sleep Quality index to measure sleep quality	Baseline
Secondary	Cognitive status	Montreal Cognitive Assessment	Baseline