Limb-Girdle Muscular Dystrophy Type 2I in Norway

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Muscular Dystrophies; Limb Girdle Muscular Dystrophy; Limb Girdle Muscular Dystrophy, Type 2I; Limb Girdle Muscular Dystrophy R9 FKRP-related

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 106

Contacts and Locations

Study Locations

• Norway
  • Tromsø, Norway, 9038
    • National Neuromuscular Centre, Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The population of limb-girdle muscular dystrophy type 2I genetically confirmed in Norway and who live in Norway.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Collaborators: University of Tromso; Norwegian Muscle Disease Association (FFM); Norwegian National Advisory Unit on Rare Disorders (NKSD); Norwegian Competence Center for Sleep Disorders
• Investigators: Principal Investigator: Kjell Arne Arntzen, ph.d, University Hospital of North Norway

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
• Other Study ID Numbers: 2018/1968(REK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No