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Dystonia에서 콜린성 수용체 이미징

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.

...

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

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.

연구 유형

관찰

등록 (실제)

31

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

    • Maryland
      • Bethesda, Maryland, 미국, 20892
        • National Institutes of Health Clinical Center

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

샘플링 방법

비확률 샘플

연구 인구

Subjects will be recruited from the pool of former participants in the studies of the Human Motor Control Section including but not limited to Protocol 93-N-0202 ( Diagnosis and Natural History Protocol for Patients with Different Neurological Conditions ), through the Healthy Volunteer and Patient Recruitment Office at NIH, advertisements in Dystonia Medical Research Foundation (DMRF) and Tyler s Hope organization newsletters and on their websites, and through contacts with referring physicians following approval of this protocol. Employees of the NINDS will not be recruited, but employees of the other NIH institutes may participate.

설명

  • 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 (focal cervical or segmental with neck involvement)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 10 weeks at time of study participation

  2. Healthy volunteers will be healthy subjects without neurological or psychiatric disorders (except for stable mild anxiety or stable mild depression) 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 besides stable mild anxiety or stable mild depression, 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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 관찰 모델: CASE_CONTROL
  • 시간 관점: PROSPECTIVE

코호트 및 개입

그룹/코호트
개입 / 치료
cervical dystonia

clinically documented cervical dystonia (focal cervical or segmental with neck involvement) established by history and physical/neurological examination, at least 18 years old.

radioligand

healthy volunteers

age and sex matched healthy volunteers, at least 18 years old.

radioligand

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
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.
기간: throughout protocol

Characterization of the M2 muscarinic acetylcholine receptor binding in cervical dystonia patients as measured with high-resolution PET using [18F]FP-TZTP.

throughout protocol

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

수사관

  • 수석 연구원: Silvina G Horovitz, Ph.D., National Institute of Neurological Disorders and Stroke (NINDS)

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2016년 12월 16일

기본 완료 (실제)

2021년 11월 26일

연구 완료 (실제)

2021년 11월 26일

연구 등록 날짜

최초 제출

2016년 2월 20일

QC 기준을 충족하는 최초 제출

2016년 2월 20일

처음 게시됨 (추정된)

2016년 2월 24일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 5일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 11월 4일

마지막으로 확인됨

2026년 8월 14일

추가 정보

이 연구와 관련된 용어

기타 연구 ID 번호

  • 160064
  • 16-N-0064

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .