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Colchicine for Primary Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes (Col-DM)

2026年9月20日 更新者：Tan Tock Seng Hospital

The Role of Colchicine in Preventing Atherosclerotic Cardiovascular Disease in Type 2 Diabetes (Col-DM Study)

This study will test whether a low-cost anti-inflammatory medicine called colchicine can help protect the blood vessels of people with type 2 diabetes. Diabetes speeds up hardening of the arteries (atherosclerosis), partly because of ongoing low-grade inflammation. Colchicine has already been shown to help prevent heart attacks and strokes in people who already have heart disease; this study looks at whether it can also help prevent early blood vessel damage before heart disease develops. Around 300 adults with type 2 diabetes will be randomly assigned to take colchicine or a placebo (dummy pill) once daily for 24 weeks, in addition to their usual diabetes and heart-risk medications. Neither participants nor the study team will know who is taking colchicine or placebo. The main measurement will be the change in the thickness of the wall of the neck (carotid) artery, measured by ultrasound, which is an early sign of blood vessel disease. The study will also look at markers of inflammation in the blood, blood vessel stiffness and function, and changes in the gut bacteria.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

Cardiovascular disease remains the leading cause of death in T2DM, occurring earlier and at substantially higher rates than in the general population. Despite optimisation of conventional risk factors, residual cardiovascular risk remains high, with chronic low-grade inflammation driven by dysregulated neutrophil activity recognised as a key contributor. Patients with T2DM exhibit a distinct pro-inflammatory neutrophil phenotype characterised by increased neutrophil extracellular trap (NET) formation, heightened endothelial adherence, and altered rolling kinetics, which correlates with impaired vascular function and subclinical atherosclerosis.

Colchicine inhibits neutrophil activation, migration, and NET formation, and has demonstrated efficacy in secondary cardiovascular prevention in large randomised trials. Evidence in primary prevention, particularly in T2DM, remains limited. Col-DM takes a precision medicine approach, hypothesising that colchicine's benefit will be concentrated among T2DM patients with a high-risk inflamed neutrophil signature rather than being uniform across the broader population.

Col-DM is a 24-week, parallel-group, Phase 2 randomised controlled trial. Adults with T2DM and no prior atherosclerotic cardiovascular disease are randomised 1:1 to colchicine 0.5 mg daily or matched placebo, stratified by neutrophil inflammatory phenotype classified using a microfluidic organ-on-chip platform. The primary outcome is progression of carotid intima-media thickness (CIMT), estimated overall and separately within each neutrophil-signature stratum. Secondary outcomes cover vascular function, inflammatory and oxidative stress biomarkers, and thrombotic potential. Gut microbiome composition is examined as an exploratory outcome. All outcome measures are estimated overall and separately within each neutrophil-signature stratum. Safety is monitored by an independent Data and Safety Monitoring Committee.

研究の種類

介入

入学 (推定)

300

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

  • シンガポール
    • Singapore
      • Singapore、Singapore、シンガポール、308433
        • 募集
        • Tan Tock Seng Hospital
        • コンタクト：
        • 主任研究者：
          • Rinkoo Dalan, MD, PhD
        • 副調査官：
          • Ying Jie Chee, MD
        • 副調査官：
          • Rupesh Agrawal, M Med (Ophth), MD (Research)
        • 副調査官：
          • Huiling Liew, MD
        • 副調査官：
          • Ying Shan Lee, MBBS
        • 副調査官：
          • Eugene Fan, MD

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

21年～80年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  • T2DM on stable diabetes medications (no change in last 3 months)
  • At least one other comorbidity of hypertension, dyslipidaemia and/or obesity (BMI ≥27), with no previous history of ASCVD
  • Able to provide informed consent

Exclusion Criteria:

  1. Recent hospitalization or acute infections within last 2 weeks.
  2. Current Treatment with corticosteroids or immunosuppressive agents
  3. Pre-existing malignancies or other terminal conditions with limited prognosis
  4. Pregnancy
  5. Breastfeeding
  6. Inability to provide written consent
  7. Renal impairment (eGFR< 60ml/min)
  8. Liver cirrhosis or ALT/AST >3x ULN
  9. Pharmacogenomics indicative of adverse effects
  10. Hypersensitivity to the active substance or to the following excipients: Lactose, Maize starch, Sodium laurilsulfate, Magnesium stearate
  11. Known blood dyscrasia
  12. Women of childbearing age who are keen to conceive in the next 1 year
  13. Taking a strong P-glycoprotein inhibitor (e.g. cyclosporine, ranolazine) or a strong CYP3A4 inhibitor
  14. Known myositis with raised creatine kinase with statins (statin myopathy).
  15. Gout attack within the last 1 year
  16. Currently taking Aspirin
  17. Taking any oral contraceptives

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：防止
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：Colchicine

Colchicine 0.5 mg orally once daily for 24 weeks, in addition to usual risk-factor-based therapy
薬：Colchicine 0.5 MG Oral Tablet Once Daily

For 24 weeks
プラセボコンパレーター：Placebo

Matched placebo orally once daily for 24 weeks, in addition to usual risk-factor-based therapy
薬：Placebo

Matched placebo tablets (identical in size, shape, taste, and packaging to colchicine), once daily, for 24 weeks

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Change from Baseline in Mean-Maximum Carotid Intima-Media Thickness (Mean-Maximum CIMT)
時間枠：Baseline and 24 weeks

Mean-maximum CIMT is defined as the average of the maximum CIMT values obtained from the far wall of the left and right common carotid arteries, each derived from six measurements taken across three projections (lateral, anterior, and posterior) at 1 cm proximal to the carotid bifurcation, measured by high-resolution B-mode carotid ultrasonography.
Baseline and 24 weeks

二次結果の測定

結果測定
メジャーの説明
時間枠
Change from Baseline in Mean Carotid Intima-Media Thickness (avgCIMT)
時間枠：Baseline and 24 weeks

Mean CIMT (avgCIMT) is defined as the average of all twelve individual IMT measurements obtained from the far wall of the left and right common carotid arteries (six measurements per side), measured by high-resolution B-mode carotid ultrasonography.
Baseline and 24 weeks
Change from Baseline in Carotid Plaque Volume
時間枠：Baseline and 24 weeks

Carotid plaque volume is measured using 3D plaque volume software following standard acquisition protocol in participants with identified carotid plaque on ultrasonography.
Baseline and 24 weeks
Change from Baseline in Endothelial Function (Flow-Mediated Dilation)
時間枠：Baseline and 24 weeks

Endothelial function is assessed by flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound, expressed as the percentage change in brachial artery diameter following reactive hyperaemia.
Baseline and 24 weeks
Change from Baseline in Microvascular Reactivity (Reactive Hyperaemia Index)
時間枠：Baseline and 24 weeks

Microvascular reactivity is assessed by the reactive hyperaemia index (RHI) measured using EndoPAT, a non-invasive device that quantifies peripheral arterial tone response to forearm occlusion.
Baseline and 24 weeks
Change from Baseline in Arterial Stiffness (Pulse Wave Velocity)
時間枠：Baseline and 24 weeks

Arterial stiffness is assessed by carotid-femoral pulse wave velocity (PWV) measured using SphygmoCor XCEL, a validated applanation tonometry-based device.
Baseline and 24 weeks
Change from Baseline in Arterial Stiffness (Cardio-Ankle Vascular Index)
時間枠：Baseline and 24 weeks

Arterial stiffness is additionally assessed by the cardio-ankle vascular index (CAVI), a measure of arterial stiffness from the origin of the aorta to the ankle that is less dependent on blood pressure at the time of measurement.
Baseline and 24 weeks
Change from Baseline in Skin Advanced Glycation End Products (Skin Autofluorescence)
時間枠：Baseline and 24 weeks

Tissue advanced glycation end product (AGE) accumulation is measured non-invasively using the AGE Reader, which quantifies skin autofluorescence using ultraviolet light excitation.
Baseline and 24 weeks
Change from Baseline in Retinal Layer Thickness (Optical Coherence Tomography)
時間枠：Baseline and 24 weeks

Retinal layer thickness is measured by optical coherence tomography (OCT) as a surrogate of retinal and systemic microvascular health.
Baseline and 24 weeks
Change from Baseline in Retinal Microvascular Density (Optical Coherence Tomography Angiography)
時間枠：Baseline and 24 weeks

Retinal microvascular density is measured by optical coherence tomography angiography (OCTA) as a surrogate of systemic microvascular health.
Baseline and 24 weeks
Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
時間枠：Baseline and 24 weeks

Serum high-sensitivity C-reactive protein (hsCRP) is measured as a marker of systemic inflammation.
Baseline and 24 weeks
Change from Baseline in Interleukin-6 (IL-6)
時間枠：Baseline and 24 weeks

Plasma interleukin-6 (IL-6) is measured as a marker of systemic inflammation and cytokine activity.
Baseline and 24 weeks
Change from Baseline in Plasminogen Activator Inhibitor-1 (PAI-1)
時間枠：Baseline and 24 weeks

Plasma plasminogen activator inhibitor-1 (PAI-1) is measured as a marker of impaired fibrinolysis and endothelial dysfunction.
Baseline and 24 weeks
Change from Baseline in Cell-Free DNA (NETosis Marker)
時間枠：Baseline and 24 weeks

Plasma cell-free DNA is measured as a marker of neutrophil extracellular trap (NET) formation and neutrophil-mediated inflammatory activity.
Baseline and 24 weeks
Change from Baseline in Citrullinated Histone H3 (NETosis Marker)
時間枠：Baseline and 24 weeks

Plasma citrullinated histone H3 is measured as a specific marker of neutrophil extracellular trap (NET) formation and NETosis.
Baseline and 24 weeks
Change from Baseline in E-selectin
時間枠：Baseline and 24 weeks

Plasma E-selectin is measured as a marker of endothelial activation and inflammation.
Baseline and 24 weeks
Change from Baseline in Intercellular Adhesion Molecule-1 (ICAM-1)
時間枠：Baseline and 24 weeks

Plasma ICAM-1 is measured as a marker of endothelial activation and leucocyte adhesion.
Baseline and 24 weeks
Change from Baseline in Vascular Cell Adhesion Molecule-1 (VCAM-1)
時間枠：Baseline and 24 weeks

Plasma VCAM-1 is measured as a marker of endothelial activation and vascular inflammation.
Baseline and 24 weeks
Change from Baseline in Oxidative Stress Index
時間枠：Baseline and 24 weeks

An integrated oxidative stress index is derived from nuclear magnetic resonance (NMR)-based redox profiling of plasma and erythrocytes, providing a composite measure of systemic oxidative stress.
Baseline and 24 weeks
Change from Baseline in Thrombotic Potential (Clot Waveform Analysis)
時間枠：Baseline and 24 weeks

Clot waveform analysis is performed to characterise the kinetics of clot formation and fibrinolysis in plasma as a measure of overall thrombotic potential.
Baseline and 24 weeks
Change from Baseline in Von Willebrand Factor Antigen (VWF:Ag)
時間枠：Baseline and 24 weeks

Plasma von Willebrand factor antigen (VWF:Ag) is measured as a marker of endothelial activation and thrombotic risk.
Baseline and 24 weeks
Change from Baseline in Von Willebrand Factor Activity (VWF:Act)
時間枠：Baseline and 24 weeks

Plasma von Willebrand factor activity (VWF:Act) is measured as a functional marker of thrombotic risk and platelet adhesion capacity.
Baseline and 24 weeks
Change from Baseline in Factor VIII
時間枠：Baseline and 24 weeks

Plasma factor VIII levels are measured as a marker of coagulation activation and thrombotic potential.
Baseline and 24 weeks
Change from Baseline in Thrombin Generation
時間枠：Baseline and 24 weeks

Thrombin generation is measured using a calibrated automated thrombogram to assess overall coagulation potential and thrombotic risk.
Baseline and 24 weeks
Change from Baseline in Oxidised LDL (Ox-LDL)
時間枠：Baseline and 24 weeks

Plasma oxidised LDL (Ox-LDL) is measured by nuclear magnetic resonance (NMR) spectroscopy as a marker of lipid oxidation and atherogenic risk.
Baseline and 24 weeks
Change from Baseline in Atherogenic Lipid Subfractions
時間枠：Baseline and 24 weeks

Atherogenic lipid subfractions are characterised by nuclear magnetic resonance (NMR) spectroscopy, providing detailed lipoprotein particle profiling beyond standard lipid panels.
Baseline and 24 weeks

その他の成果指標

結果測定
メジャーの説明
時間枠
Change from Baseline in Gut Microbiome Composition
時間枠：Baseline and 24 weeks

Gut microbiome composition is characterised from stool samples by metagenomic sequencing, to examine whether colchicine-associated shifts in microbial composition relate to treatment response.
Baseline and 24 weeks
Change from Baseline in Plasma Metabolite Profile (Metabolomics)
時間枠：Baseline and 24 weeks

As an exploratory analysis, plasma metabolomic profiling will be performed on stored blood samples to characterise changes in the metabolite profile over 24 weeks.
Baseline and 24 weeks
Incidence of Adverse Events and Serious Adverse Events
時間枠：From randomisation through 24 weeks

Safety is assessed by the incidence of adverse events (AEs) and serious adverse events (SAEs), defined per standard regulatory criteria, ascertained at each study visit and telephone contact, and adjudicated by an independent Data and Safety Monitoring Committee.
From randomisation through 24 weeks

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Tan Tock Seng Hospital

協力者

Nanyang Technological University

捜査官

  • 主任研究者：Rinkoo Dalan, MD, PhD、Tan Tock Seng Hospital

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2025年7月24日

一次修了 (推定)

2027年7月31日

研究の完了 (推定)

2027年7月31日

試験登録日

最初に提出

2026年9月6日

QC基準を満たした最初の提出物

2026年9月20日

最初の投稿 (実際)

2026年9月24日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月24日

QC基準を満たした最後の更新が送信されました

2026年9月20日

最終確認日

2026年8月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • NHG Health DSRB Ref: 2024-3120

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

IPD プランの説明

The individual participant data will not be publicly shared due to patient confidentiality restrictions and institutional data governance requirements. Researchers seeking access for secondary analyses may contact the study team to discuss feasibility, subject to a formal data sharing or research collaboration agreement with the institution.

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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