Limb-Girdle Muscular Dystrophy Type 2I in Norway

• ClinicalTrials.gov Identifier: NCT03930628
• Recruitment Status: Active, not recruiting
• First Posted: April 29, 2019
• Last Update Posted: November 7, 2022
• 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
• Information provided by (Responsible Party): University Hospital of North Norway

Study Description

Brief 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.

Condition or disease
Limb Girdle Muscular Dystrophy, Type 2I; Limb Girdle Muscular Dystrophy; Muscular Dystrophies; 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 Design

• Study Type: Observational
• Estimated Enrollment: 106 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Limb-Girdle Muscular Dystrophy Type 2I in Norway - a Cohort Study
• Actual Study Start Date: January 6, 2020
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2023

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Echo intensity of muscles [ Time Frame: Baseline and 2 years ]
   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.
2. Muscle thickness [ Time Frame: Baseline and 2 years ]
   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.
3. Age at important disease stages [ Time Frame: Retrospective data collection at baseline ]
   Document the variation in age of onset, age of loss of walking ability, age of established cardiac failure and age of established respiratory failure.
4. Rate of symptom progression [ Time Frame: Retrospective data collection at baseline ]
   Document the variation in time from disease onset to loss of walking ability
5. Prevalence of recognized cardiomyopathy [ Time Frame: Retrospective data collection at baseline ]
   The percentage of females and males with recognized cardiomyopathy
6. Prevalence of initiated ventilation support [ Time Frame: Retrospective data collection at baseline ]
   The percentage of female and males that have initiated ventilation support.
7. Motor task performance [ Time Frame: Baseline and 2 years ]
   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.
8. Disease-specific health-related quality of life (HRQOL) [ Time Frame: Baseline, at 6 months, 1 year ]
   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.
9. Echocardiography strain speckle-tracking [ Time Frame: Baseline and 2 years ]
   Measure cardiac function at baseline and changes from baseline at 2 years
10. Nocturnal arterial carbon dioxide (CO2)-level [ Time Frame: Baseline ]
    Monitor transcutaneous CO2 during sleep at baseline.
11. MRI [ Time Frame: At 2 years ]
    Muscle MRI lower limbs

Secondary Outcome Measures :

1. 6 Minute Walk Test (6MWT) [ Time Frame: Baseline (2 tests with 1 day interval) and two years (2 tests with 1 day interval) ]
   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
2. 4-step stair climb test [ Time Frame: Baseline and 2 years ]
   Changes from baseline in time to ascend and to descend a 4-steps stair at two years
3. Level of motor independence: "Vignos Grade" [ Time Frame: Baseline and 2 years ]
   Using "Vignos grade" to score level of motor independence. The score ranges from 1 (walk and climb without assistance) to 10 (confined to bed).
4. Upper limb movement ability: "Brooks Grade" [ Time Frame: Baseline and 2 years ]
   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.
5. Hand held dynamometry [ Time Frame: Baseline and 2 years ]
   Changes from baseline in muscular strength in the limbs at two years
6. Manual Muscular Testing (MMT) [ Time Frame: Baseline and 2 years ]
   Changes from baseline in muscular strength in the limbs at two years
7. General health-related quality of life [ Time Frame: Baseline, 6 months, 1 year ]
   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.
8. Plethysmography [ Time Frame: Baseline and 2 years ]
   Lung volumes at baseline, and changes from baseline at two years.
9. Mean Inspiratory and Expiratory Pressure (MIP/MEP) [ Time Frame: Baseline and 2 years ]
   Static respiratory pressures at baseline, and changes from baseline at two years
10. Forced Vital Capacity (FVC) [ Time Frame: Baseline and 2 years ]
    Dynamic spirometry while sitting, and supine when normal sitting. Baseline and changes from baseline at 2 years
11. Diaphragm thickness ratio [ Time Frame: Baseline and 2 years ]
    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.
12. Nocturnal oxygen saturation [ Time Frame: Baseline and 2 years ]
    Monitor transcutaneous oxygen saturation during sleep.
13. Cough Peak Flow [ Time Frame: Baseline and 2 years ]
    Cough Peak Flow at baseline and changes from baseline at 2 years
14. Apnea-hypopnea index [ Time Frame: Baseline ]
    Using polysomnography to calculate the number of obstructive and non-obstructive apnea and hypopnea events pr hour sleep.
15. Respiratory disturbance index [ Time Frame: Baseline ]
    Using polysomnography to calculate the number of respiratory events in terms of apneas, hypopneas and respiratory effort-related arousals pr hour sleep.
16. Thoracoabdominal breathing pattern during sleep [ Time Frame: Baseline ]
    Using polysomnography to detect paradoxal breathing movements during sleep (abdomen moving in on inspiration when supine).
17. Echocardiography - conventional [ Time Frame: Baseline and 2 years ]
    Measure cardiac function at baseline and changes from baseline at 2 years
18. Electrocardiography (ECG) [ Time Frame: Baseline and 2 years ]
    Assessment of cardiac electrical activity at baseline and changes from baseline at 2 years
19. Pain (visual analogous scale, VAS) [ Time Frame: Baseline and 2 years ]
    Patient-reported pain on VAS at baseline and at 2 years
20. Fatigue (Visual Analogous Scale, VAS) [ Time Frame: Baseline and 2 years ]
    Patient-reported fatigue on VAS tat baseline and at 2 years
21. Fatigue Severity Scale (FSS) [ Time Frame: Baseline and 2 years ]
    Fatigue at baseline and at 2 years
22. Epworth Sleepiness Scale (ESS) [ Time Frame: Baseline ]
    Assessment of daytime sleepiness at baseline
23. Capillary blood gas [ Time Frame: Baseline and 2 years ]
    Capillary CO2 at baseline and at 2 years
24. Serum Creatine Kinase (s-CK) [ Time Frame: Baseline ]
    s-CK at baseline and at 2 years
25. Insomnia [ Time Frame: Baseline ]
    Using Bergen Insomnia Scale to measure insomnia.
26. Sleep quality [ Time Frame: Baseline ]
    Using Pittsburgh Sleep Quality index to measure sleep quality
27. Cognitive status [ Time Frame: Baseline ]
    Montreal Cognitive Assessment

Biospecimen Retention:   Samples Without DNA

Serum

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

Locations

Norway

National Neuromuscular Centre, Norway

Tromsø, Norway, 9038

Sponsors and Collaborators

University Hospital of North Norway

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

More Information

• Responsible Party: University Hospital of North Norway
• ClinicalTrials.gov Identifier: NCT03930628
• Other Study ID Numbers: 2018/1968(REK)
• First Posted: April 29, 2019
• Last Update Posted: November 7, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn