Dystonia Genotype-Phenotype Correlation

June 21, 2023 updated by: Jeff Waugh, MD, PhD, University of Texas Southwestern Medical Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Investigators will recruit both healthy participants and individuals diagnosed with dystonia of any form for this study. Each Dystonia subject will be matched 1:1 with an unrelated control subject based on: 1) age, +/- 3 years (adults), +/- 1 year (16-18y), +/- 6 months (11-15y); 2) handedness, as determined by the Edinburgh Handedness Inventory, 3) gender, and 4) self-identified racial or ethnic background.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Other: Magnetic Resonance Imaging
Study interventions are minimal risk.
Other Names:
  • Blood Draw for Genetic testing
  • Clinical Assessments
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.
Other: Magnetic Resonance Imaging
Study interventions are minimal risk.
Other Names:
  • Blood Draw for Genetic testing
  • Clinical Assessments

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Structural or functional imaging of dystonia and control groups
Time Frame: 3-5 hours at each study visit
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
Genetic Analysis of dystonia and control groups
Time Frame: 30 min
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2018

Primary Completion (Estimated)

February 21, 2024

Study Completion (Estimated)

February 21, 2024

Study Registration Dates

First Submitted

February 2, 2018

First Submitted That Met QC Criteria

February 2, 2018

First Posted (Actual)

February 9, 2018

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 21, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 122017-069

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data and/or sample collection was specifically for research and subjects indicated that their data could be shared with other scientists. Investigators will only send coded data and/or samples with no identifying information. In addition, all whole blood for DNA samples collected for this protocol will be sent for DNA sequencing and genetic analysis at Massachusetts General Hospital in Dr. Nutan Sharma's lab. In addition at Massachusetts General Tissue Culture Core in the Dystonia Partners Research Biobank investigators will contribute the subject's deidentified DNA sample from this protocol for use in future genetic research regarding dystonia.

IPD Sharing Time Frame

DNA samples will be stored indefinitely

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dystonia

Clinical Trials on Magnetic Resonance Imaging

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe