Cholinergic Receptor Imaging in Dystonia
- Conditions
- Cervical DystoniaDystoniaMovement DisorderFocal Dystonia
- Interventions
- Drug: [18F]FP-TZTP
- Registration Number
- NCT02689466
- Brief Summary
Background:
Dystonia is a movement disorder in which a person s muscles contract on their own. This causes different parts of the body to twist or turn. The cause of this movement is unknown. Researchers think it may have to do with a chemical called acetylcholine. They want to learn more about why acetylcholine in the brain doesn t work properly in people with dystonia.
Objective:
To better understand how certain parts of the brain take up acetylcholine in people with dystonia.
Eligibility:
Adults at least 18 years old who have DYT1 dystonia or cervical dystonia.
Healthy adult volunteers.
Design:
Participants will be screened with a medical history, physical exam, and pregnancy test.
Study visit 1:
Participants will have a magnetic resonance imaging (MRI) scan of the brain. The MRI scanner is a metal cylinder in a strong magnetic field that takes pictures of the brain. Participants will lie on a table that slides in and out of the cylinder.
Study visit 2:
Participants will have a positron emission tomography (PET) scan. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A small amount of a radioactive chemical that can be detected by the PET scanner will be given through an IV line to measure how the brain takes up acetylcholine.
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- Detailed Description
Dystonia is a heterogeneous group of movement disorders characterized by abnormal muscle contractions resulting in abnormal postures and movements. The spectrum of dystonia includes focal, segmental, multifocal, and generalized presentations with a broad range of age of onset. An example of a focal dystonia is cervical dystonia. The pathophysiology of dystonia is unclear, but prior neuroimaging and neuropathological studies have identified a role for the basal ganglia. In neuroimaging studies, microstructural changes in the basal ganglia have been found in voxel based morphometry (VBM) and diffusion tensor imaging (DTI), and abnormal basal ganglia metabolism has been seen in imaging with fluorodeoxyglucose positron emission tomography (FDG-PET) in various types of dystonia. Basal ganglia pathology has been observed, including a case series reporting neuronal loss in the striatum. There is further evidence implicating the basal ganglia in dystonia from studies of animal models. In animal models, experimental lesions of the basal ganglia induced dystonia. An abnormality in cholinergic neurotransmission has been has also been suggested because of a clinical response to antimuscarinic medications. The striatum is a site of acetylcholine synthesis, and expresses muscarinic receptors. While antimuscarinic medications are useful in the symptomatic treatment of dystonia, the role of muscarinic acetylcholine neurotransmission in dystonia is unclear.
Objective
The objective of this application is to determine the role played by a major basal ganglia neurotransmitter, acetylcholine, in the pathophysiology of primary dystonia. The central hypothesis is that cholinergic neurotransmission is deficient in the striatum in dystonia.
Study Population
We plan to examine one group of patients with a form of primary dystonia (cervical dystonia) to be compared with healthy volunteers without history of neurological or major psychiatric disorders (stable mild anxiety or stable mild depression are allowed).
Design
This is a case-control study. Using a neuroimaging technique, position emission tomography (PET), the central hypothesis will be tested by pursuing one specific aim: to map M2 muscarinic acetylcholine receptor binding in cervical dystonia as measured with PET using \[18F\]FP-TZTP.
Outcome Measures
This study will determine cholinergic neurotransmitter receptor binding in patients with cervical dystonia compared with healthy controls. This proposed research study is expected to advance our understanding of the pathophysiology of dystonia in order to identify possible targets for potential pharmacological treatments in dystonia and monitor disease progression.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description cervical dystonia [18F]FP-TZTP clinically documented cervical dystonia (focal cervical or segmental with neck involvement) established by history and physical/neurological examination, at least 18 years old. healthy volunteers [18F]FP-TZTP age and sex matched healthy volunteers, at least 18 years old.
- Primary Outcome Measures
Name Time Method Characterize the M2 muscarinic acetylcholine receptor binding in DYT1 dystonia and cervical dystonia patients as measured with high-resolution positron emission tomography (PET) using [18F]FP-TZTP. throughout protocol Characterization of the M2 muscarinic acetylcholine receptor binding in cervical dystonia patients as measured with high-resolution PET using \[18F\]FP-TZTP.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States