Laryngeal Dystonia Clinical Trial
Official title:
Imaging Genetics of Laryngeal Dystonia
The contribution of genetic risk factors to the development of focal dystonias is evident. However, understanding of how variations in the causative gene expression lead to variations in brain abnormalities in different phenotypes of dystonia (e.g., familial, sporadic) remains limited. The research program of the investigators is set to determine the relationship between brain changes and genetic risk factors in laryngeal dystonia (or spasmodic dysphonia). The researchers use a novel approach of combined imaging genetics, next-generation DNA sequencing, and clinical-behavioral testing. The use of a cross-disciplinary approach as a tool for the discovery of the mediating neural mechanisms that bridge the gap from DNA sequence to the pathophysiology of dystonia holds a promise for the understanding of the mechanistic aspects of brain function affected by risk gene variants, which can be used reliably for the discovery of associated genes and neural integrity markers for this disorder. The expected outcome of this study may lead to better clinical management of this disorder, including its improved detection, accurate diagnosis, and assessment of the risk of developing dystonia in family members.
Status | Recruiting |
Enrollment | 410 |
Est. completion date | July 31, 2027 |
Est. primary completion date | July 31, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility | Inclusion criteria: 1. Males and females of diverse racial and ethnic background, with age across the lifespan; 2. Laryngeal Dystonia patients - phenotype: adductor or abductor - genotype: familial or sporadic 3. Voice Tremor patients - essential or - dystonic 4. Muscle tension dysphonia patients 5. Unaffected relatives of laryngeal dystonia patients with - familial laryngeal dystonia - early-onset laryngeal dystonia (onset at = 35 y.o.) - typical onset laryngeal dystonia (onset at = 40 y.o.) 6. Native English speakers. 7. Right-handedness. 8. Normal cognitive status. Exclusion criteria: 1. Subjects who are incapable of giving informed consent. 2. Pregnant or breastfeeding women until a time when they are no longer pregnant or breastfeeding. 3. Subjects with past or present medical history of (a) major neurological problems, such as stroke, movement disorders (other than LD and VT in the patient groups), brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence; (b) psychiatric problems, such as schizophrenia, bipolar depression, obsessive-compulsive disorder; (c) laryn¬geal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis. 4. Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles. 5. Subjects who receive medication(s) affecting the central nervous system. 6. Subjects with a history of major brain and/or laryngeal surgery. 7. Subjects who have tattoos, ferromagnetic objects in their bodies that cannot be removed for imaging study participation. |
Country | Name | City | State |
---|---|---|---|
United States | Massachusetts Eye and Ear Infirmary | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Kristina Simonyan | National Institute on Deafness and Other Communication Disorders (NIDCD) |
United States,
Battistella G, Fuertinger S, Fleysher L, Ozelius LJ, Simonyan K. Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia. Eur J Neurol. 2016 Oct;23(10):1517-27. doi: 10.1111/ene.13067. Epub 2016 Jun 27. — View Citation
Battistella G, Termsarasab P, Ramdhani RA, Fuertinger S, Simonyan K. Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks. Cereb Cortex. 2017 Feb 1;27(2):1203-1215. doi: 10.1093/cercor/bhv313. — View Citation
Bianchi S, Battistella G, Huddleston H, Scharf R, Fleysher L, Rumbach AF, Frucht SJ, Blitzer A, Ozelius LJ, Simonyan K. Phenotype- and genotype-specific structural alterations in spasmodic dysphonia. Mov Disord. 2017 Apr;32(4):560-568. doi: 10.1002/mds.26 — View Citation
Fuertinger S, Horwitz B, Simonyan K. The Functional Connectome of Speech Control. PLoS Biol. 2015 Jul 23;13(7):e1002209. doi: 10.1371/journal.pbio.1002209. eCollection 2015 Jul. — View Citation
Fuertinger S, Simonyan K. Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia. J Neurosci. 2017 Aug 2;37(31):7438-7449. doi: 10.1523/JNEUROSCI.0384-17.2017. Epub 2017 Jul 3. — View Citation
Putzel GG, Fuchs T, Battistella G, Rubien-Thomas E, Frucht SJ, Blitzer A, Ozelius LJ, Simonyan K. GNAL mutation in isolated laryngeal dystonia. Mov Disord. 2016 May;31(5):750-5. doi: 10.1002/mds.26502. Epub 2016 Feb 1. — View Citation
Rittiner JE, Caffall ZF, Hernandez-Martinez R, Sanderson SM, Pearson JL, Tsukayama KK, Liu AY, Xiao C, Tracy S, Shipman MK, Hickey P, Johnson J, Scott B, Stacy M, Saunders-Pullman R, Bressman S, Simonyan K, Sharma N, Ozelius LJ, Cirulli ET, Calakos N. Fun — View Citation
Simonyan K, Fuertinger S. Speech networks at rest and in action: interactions between functional brain networks controlling speech production. J Neurophysiol. 2015 Apr 1;113(7):2967-78. doi: 10.1152/jn.00964.2014. Epub 2015 Feb 11. — View Citation
Termsarasab P, Ramdhani RA, Battistella G, Rubien-Thomas E, Choy M, Farwell IM, Velickovic M, Blitzer A, Frucht SJ, Reilly RB, Hutchinson M, Ozelius LJ, Simonyan K. Neural correlates of abnormal sensory discrimination in laryngeal dystonia. Neuroimage Cli — View Citation
Vulinovic F, Schaake S, Domingo A, Kumar KR, Defazio G, Mir P, Simonyan K, Ozelius LJ, Bruggemann N, Chung SJ, Rakovic A, Lohmann K, Klein C. Screening study of TUBB4A in isolated dystonia. Parkinsonism Relat Disord. 2017 Aug;41:118-120. doi: 10.1016/j.pa — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Brain changes in laryngeal dystonia | Identify imaging biomarker of laryngeal dystonia | 5 years | |
Secondary | Genes responsible for laryngeal dystonia | Identify genetic mutations responsible for laryngeal dystonia | 5 years |
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