질티베키맙의 항염증 효과 명시 (SPIDER)
다양한 영상 기법과 심층적인 세포 표현형 분석을 통해 질티베키맙의 항염증 효과 명시
The goal of this randomized, double blind, placebo controlled trial is to study whether ziltivekimab therapy reduces arterial wall inflammation as assessed by imaging, and reduces the systemic inflammatory tone as assessed by circulating monocytes, inflammatory biomarkers and proteomics.
연구 개요
상세 설명
Considering that ziltivekimab is currently undergoing a phase 3 CVOT trial, it is of great importance to elucidate its mechanistic effects. The objective of this study is to research whether ziltivekimab therapy for 20 weeks reduces arterial wall inflammation, as assessed by state-of-the-art imaging modalities, and reduces systemic inflammatory tone, as assessed by in depth phenotyping of circulating monocytes, inflammatory biomarkers and proteomics. The imaging modalities used in this study are 68Ga-DOTATATE PET/CT and CCTA. This study is designed as a single center, randomized, double-blinded, placebo-controlled intervention study in 40 atherosclerotic patients of 50 years and older with hsCRP levels of 2 mg/L and above.
연구 유형
등록 (실제)
단계
- 3단계
연락처 및 위치
연구 장소
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Amsterdam, 네덜란드, 1105AZ
- Amsterdam UMC, location AMC
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Aged 50 years and older.
- Multi-vessel coronary artery disease (defined as CAD-RADS ≥2).
- Serum hsCRP level ≥2 mg/L.
Exclusion Criteria:
- Coronary stents in situ.
- Chronic or recent (<1 month) (serious) infections and/or clinical signs of acute (serious) infection.
- History of severe auto-immune diseases, or other (severe) (recurrent or chronic) inflammatory disorders.
- Use of preventive systemic antibiotics (antibiotics used to treat latent tuberculosis are exempted).
- Stable lipid lowering treatment for less than 4 weeks, including statins, ezetimibe and PCSK9 inhibition.
- Untreated latent tuberculosis, active hepatitis B (positive HBsAg and/or positive anti-HBc with detectable HBV DNA) or C, human immunodeficiency virus (HIV) not on stable antiretroviral regimen
- Uncontrolled diabetes (HbA1c >90 mmol/mol).
- Renal insufficiency, defined as eGFR <45 ml/min/1.73 m2.
- Platelet count <120,000 and >450,000 /mm3.
- Elevated liver enzymes (>3 ULN of liver transaminases), acute liver failure or known (severe) liver disease.
- Premenopausal women not using birth-control.
- History of gastrointestinal perforation, active diverticulitis (within 5 years) or active inflammatory bowel disease (within 12 months).
- Uncontrolled hypertension (systolic >180 mmHg; diastolic >110 mmHg).
- Diagnosis of (active) malignancy in last 5 years.
- Standard contra-indications to 68Ga-DOTATATE PET, and CT based on physician's experience and current practices.
- Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Ziltivekimab
15 mg ziltivekimab subcutaneously once per month for 5 months |
Monoclonal antibody targeting IL-6
다른 이름들:
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위약 비교기: Placebo
Placebo, subcutaneously, once per month for 5 months |
Placebo |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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TBRmax coronary arteries
기간: 5.5 months
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mean percentage change in coronary arteries target to background ratio (TBRmax) |
5.5 months
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monocyte activation marker protein expression
기간: 5.5 months
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The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16. |
5.5 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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delta PCAT
기간: 5.5 months
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Difference in PCAT (CCTA derived) after ziltivekimab treatment. |
5.5 months
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Correlation delta TBRmax and CCTA derived plaque characteristics
기간: 5.5 months
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Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA. |
5.5 months
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delta SUVmax bone marrow
기간: 5.5 months
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Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment. |
5.5 months
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delta TBRmax ascending aorta
기간: 5.5 months
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Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment |
5.5 months
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changes monocyte phenotype
기간: 5.5 months
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The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile. |
5.5 months
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changes in hsCRP
기간: 5.5 months
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hsCRP (high-sensitivity C-reactive protein): mg/L |
5.5 months
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changes plasma cytokine and chemokine levels (pg/mL)
기간: 5.5 months
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TNF-α (Tumor Necrosis Factor alpha): pg/mL IL-8 (Interleukin-8): pg/mL MCP-1 (Monocyte Chemoattractant Protein-1): pg/mL |
5.5 months
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changes plasma cytokine and chemokine levels (ng/mL)
기간: 5.5 months
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sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL |
5.5 months
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공동 작업자 및 조사자
수사관
- 수석 연구원: E.S.G. Stroes, Prof.dr., Amsterdam UMC
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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. .