Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease

Charcot-Marie-Tooth Disease Clinical Trial

— IRICDE  

Official title:

Influence of Irisin on Muscle Quality in a Cohort of Charcot-Marie-Tooth Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04786522
• Other study ID #: Iri-mCMT
• Status: Completed
• Start date: November 2, 2019
• Est. completion date: December 30, 2020

Study information

• Verified date: March 2021
• Source: University of Bari
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 30, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Charcot-Marie-Tooth Disease
• Hereditary Sensory and Motor Neuropathy
• Nerve Compression Syndromes
• Tooth Diseases

Intervention

Diagnostic Test:
• Bioimpedenziometry, Handgrip strenght evaluation
The measurement of body composition was performed using Bioimpedance (BIA 101, Akern srl, Pontassieve (FI), Italy). The handgrip dynamometer (Jamar, Sammons Preston, Bolingbrook, IL, USA) was used to determine the isometric force of the forearm.
• Evaluation on blood specimens
Serum samples were assayed for calcium, phosphorus, magnesium, iron, lactate dehydrogenase (Ldh), creatine phosphokinase (Cpk), creatine kinase myocardial band (Ckmmb), myoglobin, thyroid stimulating hormone (TSH), 25(OH)-Vitamin D, osteocalcin, bone alkaline phosphatase (b-ALP), C-terminal telopeptide of type I collagen (CTX-I), haptoglobin, sclerostin, myostatin, and Irisin. Irisin serum concentrations were detected using a competitive ELISA kit (AdipoGen, Liestal, Switzerland)

Locations

Country	Name	City	State
Italy	Policlinic Hospital	Bari

Sponsors (1)

Lead Sponsor	Collaborator
University of Bari

Country where clinical trial is conducted

Italy, 

References & Publications (16)

Budziareck MB, Pureza Duarte RR, Barbosa-Silva MC. Reference values and determinants for handgrip strength in healthy subjects. Clin Nutr. 2008 Jun;27(3):357-62. doi: 10.1016/j.clnu.2008.03.008. Epub 2008 May 2. — View Citation

Chang JS, Kim TH, Nguyen TT, Park KS, Kim N, Kong ID. Circulating irisin levels as a predictive biomarker for sarcopenia: A cross-sectional community-based study. Geriatr Gerontol Int. 2017 Nov;17(11):2266-2273. doi: 10.1111/ggi.13030. Epub 2017 Apr 10. — View Citation

Colaianni G, Errede M, Sanesi L, Notarnicola A, Celi M, Zerlotin R, Storlino G, Pignataro P, Oranger A, Pesce V, Tarantino U, Moretti B, Grano M. Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Mar — View Citation

Colaianni G, Faienza MF, Sanesi L, Brunetti G, Pignataro P, Lippo L, Bortolotti S, Storlino G, Piacente L, D'Amato G, Colucci S, Grano M. Irisin serum levels are positively correlated with bone mineral status in a population of healthy children. Pediatr R — View Citation

Colaianni G, Notarnicola A, Sanesi L, Brunetti G, Lippo L, Celi M, Moretti L, Pesce V, Vicenti G, Moretti B, Colucci S, Grano M. Irisin levels correlate with bone mineral density in soccer players. J Biol Regul Homeost Agents. 2017 Oct-Dec,;31(4 suppl 1): — View Citation

Colaianni G, Storlino G, Sanesi L, Colucci S, Grano M. Myokines and Osteokines in the Pathogenesis of Muscle and Bone Diseases. Curr Osteoporos Rep. 2020 Aug;18(4):401-407. doi: 10.1007/s11914-020-00600-8. Review. — View Citation

Corrado B, Ciardi G, Bargigli C. Rehabilitation Management of the Charcot-Marie-Tooth Syndrome: A Systematic Review of the Literature. Medicine (Baltimore). 2016 Apr;95(17):e3278. doi: 10.1097/MD.0000000000003278. Review. — View Citation

Faienza MF, Brunetti G, Sanesi L, Colaianni G, Celi M, Piacente L, D'Amato G, Schipani E, Colucci S, Grano M. High irisin levels are associated with better glycemic control and bone health in children with Type 1 diabetes. Diabetes Res Clin Pract. 2018 Ju — View Citation

Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, Nieman DC, Swain DP; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespi — View Citation

Grandis M, Shy ME. Current Therapy for Charcot-Marie-Tooth Disease. Curr Treat Options Neurol. 2005 Jan;7(1):23-31. — View Citation

Guyton GP, Mann RA. The pathogenesis and surgical management of foot deformity in Charcot-Marie-Tooth disease. Foot Ankle Clin. 2000 Jun;5(2):317-26. Review. — View Citation

Kim HJ, So B, Choi M, Kang D, Song W. Resistance exercise training increases the expression of irisin concomitant with improvement of muscle function in aging mice and humans. Exp Gerontol. 2015 Oct;70:11-7. doi: 10.1016/j.exger.2015.07.006. Epub 2015 Jul — View Citation

Ma J, Chen K. The role of Irisin in multiorgan protection. Mol Biol Rep. 2021 Jan;48(1):763-772. doi: 10.1007/s11033-020-06067-1. Epub 2021 Jan 3. Review. — View Citation

Maak S, Norheim F, Drevon CA, Erickson HP. Progress and challenges in the biology of FNDC5 and irisin. Endocr Rev. 2021 Jan 25. pii: bnab003. doi: 10.1210/endrev/bnab003. [Epub ahead of print] — View Citation

Mann DC, Hsu JD. Triple arthrodesis in the treatment of fixed cavovarus deformity in adolescent patients with Charcot-Marie-Tooth disease. Foot Ankle. 1992 Jan;13(1):1-6. — View Citation

Palermo A, Sanesi L, Colaianni G, Tabacco G, Naciu AM, Cesareo R, Pedone C, Lelli D, Brunetti G, Mori G, Colucci S, Manfrini S, Napoli N, Grano M. A Novel Interplay Between Irisin and PTH: From Basic Studies to Clinical Evidence in Hyperparathyroidism. J — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Irisin level assessment	Irisin levels in the blood at enrollment	At enrollment
Primary	muscle mass assessment	Muscle mass determined by bioelectrical impedance analysis	At enrollment
Primary	muscle strenght assessment	Muscle strenght by handgrip dynamometer	At enrollment
Primary	muscle quality assessment	Muscle quality determined by bioelectrical impedance analysis	At enrollment
Primary	Correlation between irisin levels and muscle mass, muscle strenght, and muscle quality	Correlation determined by Pearson's correlation for linear regression analysis	Immediately after enrollment