MRI and Muscle Involvement in Patients With Mutations in GMPPB

Limb girdle muscular dystrophies (LGMD) are a very heterogeneous group of muscle disorders characterized by muscle weakness and atrophy of the proximal muscles of the shoulder and pelvic girdles. LGMD is classified based on its inheritance pattern and genetic cause into more than 31 different types.

A new type - type 2T has been found. The genetic cause of type 2T is mutations in Guanosine Diphosphate (GDP)-mannose pyrophosphorylase B (GMPPB). Mutations in GMPPB can also cause Congenital muscular dystrophies (CMD). Only 41 patients with mutations in GMPPB has been reported.

In this study, the investigators examine five new cases with the LGMD phenotype. The primary aim is to examine the muscle involvement using MRI.

Study Overview

• Status: Completed
• Conditions: Limb-girdle Muscular Dystrophy

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen Neuromuscular Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Persons diagnosed with mutations in GMPPB in Denmark and France are invited to the study.

Description

Inclusion Criteria:

• Persons with genetically verified mutations in GMPPB

Exclusion Criteria:

• All contraindications for undergoing an MRI scan

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with LGMD 2T; Four patients over 18 years old with genetically verified LGMD 2T.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI scan for qualitative analysis of muscle involvement	The MRI protocol include T1-weighted brain and whole body examination. Four cross-sectional slices at shoulder, lumbar back, thigh and calf are chosen for qualitative analysis using the grading scale developed by Mercuri et al. (2007).	One MRI scan per subject (exam lasts approximately 60 min.)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle biopsy for biochemical investigation	Muscle biopsies from the tibialis anterior muscle and the deltoid muscle will be analyzed for glycosylated α-dystroglycan, merosin and GMPPB. (Concentration determined by standard biochemical analysis).	One muscle biopsy per subject (last approximately 15 min.)
10 meter walk test	Measurement of the time it takes to walk 10 meters.	Exam last approximately 5 min.
Neurological examination and test of muscle strength	Muscle strength (in arms and legs) will be examined based on the Medical Research Council (MRC) scale.	Exam last approximately 15 min.
Questionnaires	Data will be collected using Minimal mental examination (MMSE) and Fatigue Severity Scale (FSS).	Data will be collected once for patients with LGMD 2T (exam last approximately 45 min.)
Heart examination	Echocardiography and Electrocardiogram (ECG).	Exam last approximately 45 min
Forced Vital Capacity (FVC)	FVC is measured as the best of three attempts using a hand-held spirometer.	Exam last approximately 15 min
Electromyography (EMG)	EMG is used for measuring nerve conducting velocity and neuromuscular activity.	Exam last approximately 30 min

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Sofie T Østergaard, Bsc., Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: December 1, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimate): December 18, 2015

Study Record Updates

• Last Update Posted (Estimate): April 6, 2016
• Last Update Submitted That Met QC Criteria: April 5, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: MRI; LGMD; GMPPB
• 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: STO-GMPPB