Dystonia Genotype-Phenotype Correlation

Dystonia Clinical Trial

Official title:

Dystonia Genotype-Phenotype Correlation: A Study to Identify Additional Genetic Associations That Contribute to Specific Dystonic Phenotypes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03428009
• Other study ID #: STU 122017-069
• Status: Recruiting
• Start date: March 1, 2018
• Est. completion date: September 2027

Study information

• Verified date: May 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Jessica Clark
• Phone: 972.655.4847
• Email: jessica.clark[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to (1) investigate the effect of known dystonia-causing mutations on brain structure and function, to (2) identify structural brain changes that differ between clinical phenotypes of dystonia, and to (3) collect DNA, detailed family history, and clinical phenotypes from patients with idiopathic dystonia with the goal of identifying new dystonia-related genes. Investigators will be recruiting both healthy control subjects and subjects with any form of dystonia. For this study there will be a maximum of two study visit involving a clinical assessment, collection of medical and family history, task training session, an MRI using the learned tasks, and finally a blood draw for genetic analysis. In total, these visits will take 3-5 hours. If the dystonia subjects receive botulinum toxin injections for treatment, the participants and their matched controls will be asked to come for a second visit.

Description:

1. Identify a cohort of individuals with known dystonia-related gene mutations, and individuals with idiopathic but presumed-genetic dystonia. Some of these individuals may receive botulinum toxin injections to treat their dystonia per standard of care; in these patients, investigators will image before and after injections to assess for imaging correlates of treatment response.

2. Analyze DNA samples from both the dystonia and healthy individual cohorts to detect the presence of mutations and/or polymorphisms in genes associated with dystonia

3. Collect systematic clinical information, including Tsui Torticollis, Burke-Fahn-Marsden, Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Voice Disability Index, Unified Myoclonus Rating Scale, Beck Depression Inventory, Beck Anxiety Inventory and Spielberg Trait Anxiety scales. Scales will be tailored to the type of dystonia, as determined by the clinician referring into the study (i.e., torticollis scales will only be performed on patients with cervical dystonia).

4. Use functional MRI (fMRI), diffusion tensor imaging (DTI), and structural MRI to a) analyze brain activity and structure pre- and post-botulinum toxin injections, b) determine how different stages of movement (execution, preparation, sequencing) influence dystonia and the underlying neural mechanisms, c) identify structural abnormalities shared between clinical sub-types of dystonia. As new MR imaging methods are introduced that may improve the investigators ability to identify or distinguish these abnormalities, the investigator will incorporate these novel sequences into the imaging protocol.

5. Correlate brain activity and structural data with ratings of dystonia severity, location of dystonia, genetic status, and response to treatment (medications and/or botulinum toxin injections).

6. Correlate polymorphism data with dystonia severity, response to botulinum toxin, depression/anxiety severity, and brain activity/structure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: September 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 11 Years and older

Eligibility

General Exclusion (both Dystonia and Control groups):

• Metal in any part of the body (including metal injury to the eye) OR carrying a medical device incompatible with MRI (e.g., metal implants such as surgical clips or pacemakers) OR positive screening per UTSW MRI screening form

• Claustrophobia

• Non-fluent English

• Weight incompatible with MRI safety

• History of head trauma with neurological sequelae, including multiple concussions and/or history of stroke

• Pregnancy

• Serious medical illness or history of serious medical illness, including cancer that was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1 + status

• Subjects with Hepatitis C (by Hepatitis C+ titer)

• Subjects with insulin dependent diabetes mellitus (IDDM)

• Severe respiratory compromise

• In the opinion of the investigator, not able to safely participate in this study

Inclusion Criteria:

• Dystonia group

Previous diagnosis of dystonia which include but is not limited to:

• cervical dystonia (50 subjects)

• blepharospasm (25 subjects)

• limb dystonia (50 subjects)

• spasmodic dysphonia (25 subjects)

• segmental dystonia

• multi-focal dystonia

• Any childhood-onset dystonia (25 subjects) Age > 11 years

• Control group:

No prior dystonia diagnosis (175 subjects) Age > 11 years

Exclusion Criteria:

• Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis - depression and/or anxiety accepted Current use of non-dystonia neuroactive medications
• SSRI/medication for depression and/or anxiety accepted Current use of cervical brace designed for dystonia treatment Prior structural brain injury

Control group:

History of or current neurological or psychiatric diagnosis - depression and/or anxiety accepted, but must not be in active phase Current use of any neuroactive medication, SSRI/medication for depression and/or anxiety accepted

Related Conditions & MeSH terms

• Dystonia
• Dystonia 10
• Dystonia 11
• Dystonia 12
• Dystonia 19
• Dystonia 20
• Dystonia 5
• Dystonia 6
• Dystonia 8
• Dystonia 9
• Dystonia Disorder
• Dystonia Lenticularis
• Dystonia of Head
• Dystonia, Diurnal
• Dystonia, Familial
• Dystonia, Focal
• Dystonia, Paroxysmal
• Dystonia, Primary
• Dystonia, Secondary
• Dystonia; Idiopathic
• Dystonia; Orofacial
• Dystonias, Sporadic
• Dystonic Disorders

Intervention

Other:
• Magnetic Resonance Imaging
Study interventions are minimal risk.

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Structural or functional imaging of dystonia and control groups	Identify structural or functional imaging measures that distinguish (a) dystonia patients from matched controls, (b) between clinically-defined forms of dystonia	3-5 hours at each study visit
Primary	Genetic Analysis of dystonia and control groups	Identify polymorphisms in genes known to cause dystonia that affect the structural or functional imaging measures in dystonia patients and to identify new genes associated with dystonia.	30 min