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Trial record 21 of 23 for:    Recruiting, Not yet recruiting, Available Studies | "Torticollis"

Cholinergic Receptor Imaging in Dystonia

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ClinicalTrials.gov Identifier: NCT02689466
Recruitment Status : Recruiting
First Posted : February 24, 2016
Last Update Posted : July 10, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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.


Condition or disease
Cervical Dystonia Dystonia Movement Disorder Focal Dystonia

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 psychiatric disorders.

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.


Study Type : Observational
Estimated Enrollment : 54 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Cholinergic Receptor Imaging in Dystonia
Study Start Date : February 20, 2016
Estimated Primary Completion Date : October 1, 2018
Estimated Study Completion Date : October 1, 2018





Primary Outcome Measures :
  1. Characterize the M2 muscarinic acetycholine receptor binding in cervical dystonia patients as measured with high-resolution positron emission tomography (PET) using [18F]FP-TZTP [ Time Frame: 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Healthy research volunteers and adult patients with cervical dystonia will be eligible for the study.

  1. Adult patients with cervical dystonia will have clinically documented cervical dystonia established by history and physical/neurological examination.

    --Cervical dystonia patients must not have had received botulinum toxin injections into neck muscles for at least about 3 months at time of study participation

  2. Healthy volunteers will be healthy subjects without neurological or psychiatric disorders established by history and physical/neurological examination.
  3. All participants will be at least 18 years of age. There is no maximum age limit.
  4. Participants must be able to abstain from tobacco or nicotine replacement for at least 3 days prior to PET scan if participating in both MRI and PET scanning..
  5. Participants must be able to abstain from caffeine for at least 24 hours prior to PET scan if participating in both MRI and PET scanning.
  6. Participants must be able to fast for 3 hours before PET scan if participanting in both MRI and PET scanning.

EXCLUSION CRITERIA:

  1. Subjects who are incapable of giving informed consent.
  2. Employees of NINDS
  3. Pregnant or breastfeeding women. Aside from history obtained at the screening, pregnancy status in women with childbearing potential is also established by urine pregnancy testing no more than 24 hours before each MRI and PET scan session.
  4. Subjects with past or present medical history of (a) neurological disorders, such as stroke, movement disorders (other than cervical dystonia in the patient group), brain tumors, traumatic brain injury with loss of consciousness lasting more than a few seconds, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence; (b) psychiatric disorders, such as schizophrenia, major depressive and/or bipolar disorder, obsessive-compulsive disorder; (c) ventricular arrhythmias, renal and hepatic insufficiency, vascular headache, or carcinoid syndrome.
  5. Abnormalities in neurological examination other what is typically associated with cervical dystonia, or any abnormalities in neurological examination in healthy volunteers.
  6. Subjects who are currently taking oral medications known to affect muscarinic acetylcholine receptor binding in the central nervous system. Of note, some over-the counter-medications are known to affect muscarinic acetylcholine receptor binding. Subjects who use medications known to affect muscarinic acetylcholine receptor binding, such as first generation antihistamines for common cold and allergy symptoms and sleep aids for insomnia, occasionally on an as needed basis may be enrolled in this study. Furthermore, these as needed medications should be paused for at least 3 days before PET scanning. This three-day period is equivalent to about 4 to 5 half lives for these medications. In addition, subjects who use topical antimuscarinic medications, such as eye drops for glaucoma and inhalers, may be enrolled in this study because topical antimuscarinic medications have negligible systemic bioavailability. Subjects who have contraindications to MRI, ferromagnetic objects in their bodies (e.g., implanted stimulators including deep brain stimulation, aneurysm clips, prosthesis, artificial heart valves, etc.) that cannot be removed for the purpose of study participation.
  7. Subjects who have claustrophobia.
  8. Subjects who are unable to lie comfortably on their back for about one hour for MRI scanning (and about two hours for PET scanning if participating in both MRI and PET scanning).
  9. Subjects with any radiation exposure in the past year that, together with the research PET scan, would exceed the NIH Radiation Safety Committee s annual limit (5 rem) if participating in both MRI and PET scanning.
  10. Cervical dystonia patients who have cervical dystonia associated with trauma

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689466


Contacts
Contact: Elaine P Considine, R.N. (301) 435-8518 considinee@ninds.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Mark Hallett, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT02689466     History of Changes
Other Study ID Numbers: 160064
16-N-0064
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: December 5, 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Adult
Acetylcholine
Movement Disorder
Magnetic Resonance Imaging (MRI)
PET Imaging

Additional relevant MeSH terms:
Torticollis
Dystonia
Dystonic Disorders
Movement Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Central Nervous System Diseases
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs