Clinical trial NCT04786522: Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
Official title: Influence of Irisin on Muscle Quality in a Cohort of Charcot-Marie-Tooth Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Charcot-Marie-Tooth Disease
Keywords: bioimpedance analysis
handgrip strength
body composition
Lead sponsor: University of Bari
Sponsor class: OTHER
First posted: 2021-03-08
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with Charcot-Marie-Tooth disease who have given informed consent

Brief summary: Irisin is an exercise-mimetic myokine secreted by skeletal muscle. Compelling evidence in animal models and humans showed that Irisin prevents onset of musculoskeletal atrophy and its low serum levels are predictive of sarcopenia. The investigators evaluated the levels of irisin in patients affected by an hereditary motor and sensory neuropathy, namely Charcot-Marie-Tooth disease (CMT), in order to investigate possible key determinants of their muscle quality and possibly prevent the progressive distal weakness and muscle atrophy.

Detailed description: Currently, there are no effective treatment approaches for CMT other than treating symptoms with medications such as nonsteroidal anti-inflammatory drugs that provide relief of lower back or leg pain. Except for the most severe cases in which orthopedic surgery is recommended to correct pes cavus and/or spine deformities, rehabilitative management of patients with CMT has shown that physical activity can provide a moderate increase in muscle strength and musculoskeletal function, improving activities of daily living. Benefits of exercise on the musculoskeletal system are widely recognized as primary non-pharmacologic intervention for several diseases. The positive outcome of physical activity is achieved not only by the mechanical load applied on the musculoskeletal system, but also via biochemical signals, the myokines, secreted during contraction that act locally or systemically on several body districts. Among these, Irisin is a hormone-peptide synthesized from skeletal muscle performing key actions on the whole-body metabolism. In humans, the investigators have documented with several studies an existing positive association between circulating levels of Irisin and bone mineral density. Very recently, in muscle biopsies of older adult subjects, the investigators also observed that the expression of the Irisin precursor, the fibronectin type III domain-containing protein 5 (FNDC5), was positively associated with Irisin serum levels and osteocalcin mRNA expression in bone biopsies, indicating a strong correlation between healthy muscle and bone tissues. In humans, low levels of circulating Irisin have been found to be predictive of muscle weakness and atrophy, and Irisin has been identified as a sensitive molecular biomarker for sarcopenia in postmenopausal women. In addition, women older than 65 years undergoing a 12-week exercise program showed an increase in circulating Irisin and an improvement in isokinetic leg strength and grip strength compared with control women. Moreover, there was a positive correlation between Irisin levels with grip strength and leg strength in the exercise group, suggesting a causal relationship between improved muscle strength and increased Irisin concentration. Although numerous reports recommend increasing muscle strength in CMT patients to prevent progressive distal weakness and muscle atrophy, few studies have investigated the possible key determinants of muscle quality in these patients. Therefore, the aim of this study was to evaluate circulating Irisin levels in a population of 20 CMT patients as well the association of Irisin with biochemical parameters and muscle quality. In addition, the investigators compared these data with unpublished data previously obtained in healthy subjects.

Eligibility criteria: Inclusion Criteria:

* Definitive diagnosis of Charcot-Marie-Tooth disease

Exclusion Criteria:

* osteoporosis
* intestinal malabsorption
* chronic inflammatory diseases
* chronic renal failure
* severe heart failure
* neoplastic diseases

Primary outcomes:
measure: Irisin level assessment
timeFrame: At enrollment
measure: muscle mass assessment
timeFrame: At enrollment
measure: muscle strenght assessment
timeFrame: At enrollment
measure: muscle quality assessment
timeFrame: At enrollment
measure: Correlation between irisin levels and muscle mass, muscle strenght, and muscle quality
timeFrame: Immediately after enrollment
Secondary outcomes:
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Policlinic Hospital
Study officials:
affiliation: University of Bari
name: Michele Barone, prof.
role: PRINCIPAL_INVESTIGATOR
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