- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00279136
Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma
연구 개요
상태
정황
상세 설명
Rationale. Asthma is associated with variable airways obstruction and airways inflammation. It is generally assumed that inflammatory mechanisms are promoting airway narrowing, by stimulating airway smooth muscle and by geometrical changes of the airway wall. Healthy subjects are very effectively protected against stimuli of airway narrowing, by mechanisms that are apparently failing in asthma. The most potent inhibitor of airway narrowing in healthy subjects is taking a deep inspiration. This prevents and reverses bronchoconstriction (DI-induced bronchoprotection and -bronchodilation, respectively), which is less effective or absent in asthma. The DI-induced inhibition of airway narrowing in normal subjects is presumably due to relaxation of smooth muscle after mechanical stretch or to the release of relaxant mediators (such as endogenous NO). Such mechanisms might have become impaired in asthma, secondary to e.g. mechanical uncoupling of smooth muscle from the surrounding parenchyma (e.g. by congestion or edema), by altered structure and function of airway smooth muscle, and/or by reduced inhibitory mediator release.
It can be postulated that the impaired response to deep inspiration is a central pathophysiological feature of asthma at all ages. Therefore, we believe that it is imperative to address this, by identifying and restoring these inhibitory pathways in patients with asthma.
Hypotheses.
We hypothesize that DI-induced bronchoprotection and -broncho¬dilation:
- are associated with cellular and morphological features of airways inflammation,
- can be restored by deep insufflation rather than deep inspiration, and by pharmacological interventions aimed to reduce microvascular congestion or to increase endogenous nitric oxide synthesis..
Design and methods. To examine to what extent DI-responses differ between asthma and COPD in adulthood, and whether this is associated with features of airways inflammation and changes in smooth muscle function. 12 Adult patients with asthma and 12 with COPD will undergo single-dose methacholine challenge, with prohibition of DI's or 5 DI's prior to challenge in a cross-over design, measuring airways resistance. On a separate day bronchial biopsies will obtained with immunohistochemistry for inflammatory cell markers, vascularity, microvascular leakage, myosin light chain kinase, NO-synthases, and arginase.
연구 유형
등록
연락처 및 위치
연구 연락처
- 이름: Peter J. Sterk, MD, PhD
- 전화번호: +31 71 526 3578
- 이메일: p.j.sterk@lumc.nl
연구 연락처 백업
- 이름: Annelies M. Slats, MD
- 전화번호: +31 71 526 3734
- 이메일: a.m.slatts@lumc.nl
연구 장소
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Leiden, 네덜란드, NL-2300 RC
- 모병
- Leiden University Medical Center
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연락하다:
- Peter J. Sterk, MD, PhD
- 전화번호: +31 71 526 3578
- 이메일: p.j.sterk@lumc.nl
-
연락하다:
- Annelies M. Slats, MD
- 전화번호: +31 71 526 3734
- 이메일: a.m.slats@lumc.nl
-
수석 연구원:
- Peter J. Sterk, MD, PhD
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Asthma according to GINA criteria (www.ginasthma.org)
- COPD according to GOLD criteria (www.goldcopd.org)
Exclusion Criteria:
- nonsmoking
- inhaled or oral steroid therapy
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
공동 작업자 및 조사자
수사관
- 연구 의자: Peter J. Sterk, MD, PhD, Leiden University Medical Center
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
연구 완료
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- AF 3.2.02.34, DIACON
- Grant AF 3.2.02.34
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