Biomarkers and Validation of Selected Outcome Measures (CMTNSmod)

Charcot-Marie-Tooth Disease, Type IA Clinical Trial

Official title:

Biomarkers and Validation of Selected Outcome Measures (CMTNSmod)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03386266
• Other study ID #: 05171
• Status: Completed
• Start date: August 11, 2017
• Est. completion date: September 30, 2019

Study information

• Verified date: November 2020
• Source: University Medical Center Goettingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

CMT is a rare disease for which novel treatments are being developed. Evaluation of intervention efficacy is hampered by slow progression and lack of sensitive outcome measures. Primary goal of the project is to identify and validate RNA and protein derived biomarkers in blood of CMT patients for selected outcome measures over 2 years. The investigators expect to develop more responsive outcome measures and circulating biomarkers to improve assessment of intervention efficacy in forthcoming therapeutic trials.

Description:

Novel treatments are being developed for CMT. Intervention efficacy evaluation is hampered by slow disease progression and lack of sensitive outcome measures. The investigators have previously shown that biomarkers from skin identified in a CMT1A rat model can be translated to CMT1A patients. Primary goal is to identify circulating biomarkers correlating with disease severity and progression. 210 young, adolescent and adult patients affected by genetically confirmed CMT1A, will be evaluated with different clinical outcome measures, assessing impairment, disability and quality of life: Patients will be re-evaluated at 12 (n=147) and 24 months (n=103) with the same measures to assess disease progression. A number of candidate markers correlating with disease severity have been identified in blood samples from the rat model of CMT1A. At 0-12-24 months a blood sample will be drawn from affected CMT1A patients. The investigators will purify total mRNA from blood samples, and validate the 10 strongest regulated markers identified in the rat model via qRTPCR in blood of CMT1A patients. Protein biomarkers will also be analysed. Marker expression at baseline and at follow up will be correlated with clinical severity and progression. In this translational project (rat/human) the investogators expect to develop more responsive outcome measures and circulating biomarkers to improve assessment of intervention efficacy in forthcoming therapeutic trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 65 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of CMT1A
• Genetic confirmation of PMP22 duplication (for adults patients)
• Children aged 3-11, adolescents aged 12-17 and adults aged 18-65 years
• Signed informed patient consent

Exclusion Criteria:

• Other causes of neurological and psychiatric disorders
• Severe internistic disease
• Patient known or suspected to be alcohol / drug abuser
• Pregnancy, breast feeding period
• Permanent Vitamin C intake
• Participation an interventional clinical study up to 4 weeks prior to inclusion

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
Germany	University Medical Center Goettingen	Goettigen	Lower Saxony

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Goettingen	Ludwig-Maximilians - University of Munich, University Hospital Muenster

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Fledrich R, Mannil M, Leha A, Ehbrecht C, Solari A, Pelayo-Negro AL, Berciano J, Schlotter-Weigel B, Schnizer TJ, Prukop T, Garcia-Angarita N, Czesnik D, Haberlová J, Mazanec R, Paulus W, Beissbarth T, Walter MC, Triaal C, Hogrel JY, Dubourg O, Schenone A — View Citation

Fledrich R, Schlotter-Weigel B, Schnizer TJ, Wichert SP, Stassart RM, Meyer zu Hörste G, Klink A, Weiss BG, Haag U, Walter MC, Rautenstrauss B, Paulus W, Rossner MJ, Sereda MW. A rat model of Charcot-Marie-Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients. Brain. 2012 Jan;135(Pt 1):72-87. doi: 10.1093/brain/awr322. Epub 2011 Dec 20. — View Citation

Mannil M, Solari A, Leha A, Pelayo-Negro AL, Berciano J, Schlotter-Weigel B, Walter MC, Rautenstrauss B, Schnizer TJ, Schenone A, Seeman P, Kadian C, Schreiber O, Angarita NG, Fabrizi GM, Gemignani F, Padua L, Santoro L, Quattrone A, Vita G, Calabrese D; CMT-TRIAAL/CMT-TRAUK Group, Young P, Laurà M, Haberlová J, Mazanec R, Paulus W, Beissbarth T, Shy ME, Reilly MM, Pareyson D, Sereda MW. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients. Neuromuscul Disord. 2014 Nov;24(11):1003-17. doi: 10.1016/j.nmd.2014.06.431. Epub 2014 Jun 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mRNA Expression Levels in blood samples from CMT1A patients	Validation of key candidate genes (GSST2, FN3KRP, CTSA, SPRR1A) fro former studies	3 years
Primary	mRNA Expression Levels in Skin biopsies from CMT1A patients	Validation of key candidate genes (GSST2, FN3KRP, CTSA, SPRR1A) fro former studies	3 years