Neuroimaging of Dystonia (NID)

Neuroimaging of Dystonia: The Bachmann-Strauss Dystonia and Parkinson Disease Center of Excellence at the University of Florida

The main purpose of this study is to investigate primary cervical dystonia as compared to healthy control subjects and DYT 1 dystonia as compared to healthy control subjects by examining cognitive measures, physical measures, and structural and functional magnetic resonance imaging (MRI).

The secondary aim of this study is to investigate a specific drug therapy for primary cervical dystonia to develop a functional MRI (fMRI) research paradigm. The drug, trihexyphenidyl, is FDA approved to treat Parkinson's Disease and is commonly prescribed by physicians as a treatment for symptoms of primary cervical dystonia.

Study Overview

• Status: Completed
• Conditions: Primary Cervical Dystonia; DYT 1 Dystonia
• Intervention / Treatment: Drug: Primary Cervical Dystonia (Trihexyphenidyl); Other: DYT 1 Dystonia (Healthy Control); Other: Controls Primary Cervical Dystonia (Trihexyphenidyl); Other: DYT 1 Dystonia

Detailed Description

To participate in this study, you will be asked to come to the University of Florida for one testing day. For your convenience, arrangements will be made by the study coordinator.

If you have a movement disorder, you will be tested in an "off" medication condition. We do not expect concerns or unwanted consequences arising from discontinuing medications for this duration.

We will review the informed consent and you will have the opportunity to ask questions before signing the informed consent. During the experiment, you may be asked to complete the following: (1) questionnaires about quality of life and depression; (2) tests to measure your strength and motor function; (3) tests to measure your cognition; (4) functional and structural MRI scan of your brain while performing a precision gripping task; (5) intravenous blood draw; (6) urine pregnancy test (if applicable); (7) trial of anticholinergic therapy drug trihexyphenidyl (if applicable - cervical dystonia only).

Participants with DYT 1 dystonia and healthy controls are not eligible to receive the trial drug. All women of childbearing potential will be given a urine pregnancy test. The questionnaire about depression will not be given to subjects under the age of 18.

If you have any metal in your eye or eyes, the researchers may require additional screening to ensure that it is safe for you to enter the MRI environment. If additional screening is determined to be necessary, you will be referred to Radiology at Shands UF for an orbitofrontal x-ray.

Blood will be collected for all subjects, including healthy control subjects. The blood may be analyzed, at the University of Florida, to assess potential biomarkers for cervical dystonia and DYT 1 dystonia. Biomarker testing is another way to say genetic testing.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32607
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Qualifying candidates with a diagnosis of DYT 1 dystonia will be identified and invited to participate utilizing an IRB approved database and neurologists review.

Description

Inclusion Criteria:

• Diagnosis of primary cervical dystonia and between the ages of 18-70, OR
• Diagnosis of DYT 1 dystonia and between the ages of 7-50, OR
• Healthy control and between the ages of 7-70

Exclusion Criteria:

• Neurological impairment from: seizure disorders, stroke, hypertension, heart disease, diabetes, traumatic brain injury (TBI), drug abuse, nerve disorders, dementia, Parkinson's Disease, dementia
• Not a candidate for magnetic resonance imaging (MRI)
• Deep brain stimulation (DBS) surgery
• Any implanted electrical device
• Pregnant or planning pregnancy
• Breastfeeding
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary Cervical Dystonia (Trihexyphenidyl); These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; and 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed. After the above baseline testing these subjects will receive a dose of trihexyphenidyl 2 mg an hour prior to the second functional fMRI scan. The subjects will be done with the study after the second MRI scan has been completed.	Drug: Primary Cervical Dystonia (Trihexyphenidyl); After the baseline testing these subjects will receive a dose of trihexyphenidyl 2 mg an hour prior to the second functional magnetic resonance imaging (fMRI) scan. This is to test the change in cerebral blood flow based on blood-oxygen-level dependent (BOLD) contrast during a precision gripping task after administration of trihexyphenidyl compared to change in BOLD contrast during a precision gripping task. The subjects will be done with the study after the second MRI scan has been completed.; Other Names: Artane; Apo-Trihex; Parkin; Pacitane; Benzhexol; Trihex; Trihexphenidyl
DYT 1 Dystonia (Healthy Control); These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; and 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed.	Other: DYT 1 Dystonia (Healthy Control); These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; and 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed.
Primary Cervical Dystonia (Healthy Control); These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; and 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed.	Other: Controls Primary Cervical Dystonia (Trihexyphenidyl); These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; and 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed.
DYT 1 Dystonia; These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed; and 6) Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) to assess dystonia severity.	Other: DYT 1 Dystonia; These subjects will receive the following: 1) data about clinical movement disorder history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, and Brief Test of Attention (BTA); 4) measures of anxiety and depression: the Beck Depression Index (BDI II). Only participants aged 18+ will be given the BDI; and 5) Functional magnetic resonance imaging (fMRI) and structural MRI will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cerebral blood flow based on blood-oxygen-level dependent (BOLD) contrast during a precision gripping task	Participants will use their hand to squeeze an MRI compatible grip force transducer in the MRI unit. While producing force, the participants will observe the amount of force generated by viewing a visual feedback display.	1 hour
Change in cerebral blood flow based on blood-oxygen-level dependent (BOLD) contrast during a precision gripping task after administration of trihexyphenidyl compared to change in BOLD contrast during a precision gripping task	Subjects with primary cervical dystonia will repeat the primary outcome measure "Change in cerebral blood flow based on blood-oxygen-level dependent (BOLD) contrast during a precision gripping task" one hour after administration of 2mg trihexyphenidyl tablet.	2 hours

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Bachmann Strauss Dystonia & Parkinson Foundation, Inc.
• Investigators: Principal Investigator: Michael Okun, MD, University of Florida; Principal Investigator: David Vaillancourt, PhD, University of Florida

Publications and helpful links

Helpful Links

• UF Center for Movement Disorders & Neurorestoration
• Tyler's Hope for a Dystonia Cure

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: January 23, 2014
• First Posted (Estimate): January 27, 2014

Study Record Updates

• Last Update Posted (Actual): December 22, 2017
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: fMRI; healthy; dystonia; cervical dystonia; Parkin; DYT1; trihexyphenidyl; DYT-1; DYT 1; Dystonia 1; Artane; Apo-Trihex; Pacitane; Benzhexol; Trihex
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Trihexyphenidyl
• Other Study ID Numbers: 354-2013