Desminopathy G71.8
Conditions
Interventions
Group 1: Patients with the disease desminopathy:
Day 1: blood collection, insulin sensitivity, questionnaires, MRI.
Day 2: body composition, anatomical landmarks, 4m max walk test and grip strength, v
Sponsors
DLR Institut für Luft- und Raumfahrtmedizin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Group A: genetically diagnosed with desminopathy Group B: matched by sex, age and height to a participant of group A Both groups: Signed informed consent
Exclusion criteria
Exclusion criteria: Group A: - any cardiac condition that preclude participation in the study Group B: - diagnosed with any musculoskeletal disorder likely to interfere with endpoints of the study, e.g. with a genetic exclusion of a desmin gene mutation. Both groups: - Contra-indications against biopsy (e.g. impaired hemostasis, keloidosis, history of adverse reactions to local anesthesia or to surgical procedures) - Contra-indications against magnetic resonance imaging (e.g. claustrophobia, ferromagnetic or electronic implants)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endpoints: Metabolic in vivo analyses - PCr (31P-magnetic resonance spectroscopy, (31P MRS)) depletion in fatigue test - PCr-recovery after fatigue test - Insulin sensitivity (via euglycemic hyperinsulinemic clamp) - Physiological cross section of the knee extensor muscles - Knee extensor muscle tissue stress during maximal voluntary contraction - Lipid content of the liver and muscle (1H-MRS) - Abdominal fat (6-point Dixon magnetic resonance imaging (6-point Dixon MRI)) Mechanical in vivo analyses - Muscle strength and power (MARES) - Neuro-muscular stiffness (MARES) - Muscle architecture and shear wave velocity (ultrasound) - Muscle stress during maximal voluntary contraction (computed from dynamometry and physiological muscle cross-section) From muscle biopsy - “complete” myopathological analysis (light microscopy + electron microscopy) - Mitochondrial function (Polarography) - Mitochondrial content (citrate synthase activity, mtDNA copy number) - Oxidative stress (mitochondrial and plasma oxidation-reduction potential) - Endomysium content - Proteomics - Intramyocellular neutral fat content - RNAseq From blood sample - routine laboratory blood parameters (glucose, insulin, lactate, pyruvate, free-fatty acids, total cholesterol, LDL-C, HDL-C, creatinine, AST, ALT, gammaGT, hsCRP, thyroxin, TSH, HbA1c, albumin, electrolytes, glucagon, CK, LDH, troponin, BNP, - Carnitine and acylcarnitine profiles (mass spec analysis via dried blood sample cards) - markers of biological age: “DNAge” based on CpG DNA methylation pattern of 6 selected genes - blood circulating myo-microRNAs. - blood gas analysis Exploratory Analysis: - substrate utilization (via indirect calorimetry) and lactate/pyruvate ratio before and during euglycemic hyperinsulinemic clamp - Vertical jump performance - Body composition (BIA, BodPod) - Skeletal muscle volume and composition (MRI) - Cardio-MRI and 1H-MRS - lactate/pyruvate ratio - 4m walking test & grep strength for assessment of sarcop | — |
Countries
Germany
Contacts
Public ContactJörn Rittweger
Institut für Luft- und Raumfahrtmedizin
Outcome results
None listed