Dystonia Genotype-Phenotype Correlation

NCT ID: NCT03428009

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2027-09-30

Brief 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.

Detailed 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.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Dystonia group

Both groups will have blood drawn, undergo clinical assessments, the collection of medical and family history, and an Magnetic Resonance Imaging. This is an observational study and there is no intervention.

Magnetic Resonance Imaging

Intervention Type: OTHER

Study interventions are minimal risk.

Control Group

Both groups will have blood drawn, undergo clinical assessments, the collection of medical and family history, and an Magnetic Resonance Imaging. This is an observational study and there is no intervention.

Magnetic Resonance Imaging

Intervention Type: OTHER

Study interventions are minimal risk.

Interventions

Magnetic Resonance Imaging

Study interventions are minimal risk.

Intervention Type: OTHER

Other Intervention Names

Blood Draw for Genetic testing; Clinical Assessments

Eligibility Criteria

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

• 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

• 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

• Minimum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jeff Waugh, MD, PhD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Alyssa Boudreau

Role: CONTACT

alyssa.boudreau@utsouthwestern.edu

214-456-2106

Jeff Waugh, MD, PhD

Role: CONTACT

Jeff.Waugh@UTSouthwestern.edu

214-867-6906

Facility Contacts

Alyssa Boudreau

Role: primary

alyssa.boudreau@utsouthwestern.edu

214-456-2106

Jeff Waugh, MD/PhD

Role: backup

jeff.waugh@utsouthwestern.edu

Other Identifiers

STU 122017-069

Identifier Type: -

Identifier Source: org_study_id