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治験 NCT05478707 (KML002)(対象:1型糖尿病、内皮機能障害)は募集中です。詳細は治験レーダーのタイル表示と AI 発見ツールで確認するか、ここで質問してください。
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Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes (KML002)

募集中
治験(臨床試験)の詳細は主に英語で提供されています。しかし、治験レーダーAIが支援できます!「治験を説明」をクリックして、選択した言語で試験情報を表示し、議論してください。
治験番号 NCT05478707 (KML002) は 1型糖尿病、内皮機能障害 に関する 基礎研究 の研究で、第II相・第二段階 介入研究 臨床試験 です。現在は 募集中 で、2023年10月5日 から開始しています。64 名の参加者 の募集が計画されています。この治験は バージニア大学 によって主催され、2027年6月30日 に完了予定です。ClinicalTrials.gov からの最新更新日は 2024年11月12日 です。
概要
The investigators will test the hypothesis that, in adults with type 1 diabetes (T1D), glucagon-like peptide-1 receptor agonism (GLP-1RA, i.e. dulaglutide) and exercise training each enhance insulin-mediated skeletal muscle microvascular perfusion via attenuating endothelial oxidative stress and thereby improving endothelial function.
詳細説明
In this study, 64 (n=48 needed to complete) adult participants with type 1 diabetes will be randomized (1:1:1) to 14-weeks of one of 3 interventions: 1) dulaglutide, 2) placebo, or 3) exercise training.

Participants will undergo two study admissions at baseline and 14 weeks. Prior to each admission, participants will wear a continuous glucose monitor (Dexcom G6 Professional) for 10 days to assess glycemic variability (GV). Prior to admissions, they will undergo cardiorespiratory fitness testing. On study admission days, participants will undergo an antecubital vein endothelial cell biopsy prior to commencing vascular testing. From the harvested endothelial cells, the investigators will quantify endothelial cell reactive oxygen species (ROS) and protein expression relevant to insulin-mediated endothelial function. Vascular testing will include contrast enhanced ultrasound of quadriceps muscle to determine microvascular blood volume (MBV). The investigators will also measure brachial artery flow mediated dilation (FMD). Quadriceps skeletal muscle oxygenation (HHb) will also be measured. These vascular and muscle oxygenation measurements will be conducted before and after a 120-minute euglycemic insulin clamp which will measure insulin sensitivity based on glucose infusion rate (GIR).

This randomized, placebo-controlled study will assess whether GLP-1 receptor agonism with dulaglutide or exercise training improves insulin-mediated skeletal muscle microvascular perfusion. The investigators will assess for predictive relationships between microvascular perfusion and cardiorespiratory fitness (VO2max), insulin sensitivity (GIR), endothelial reactive oxygen species (ROS), and glycemic variability (GV).

公式タイトル

Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

疾患/病気
1型糖尿病内皮機能障害
刊行物
この臨床試験について発表された科学記事と研究論文:
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その他の研究識別子
  • KML002
  • 210198
NCT番号
開始日
2023-10-05
最終更新日
2024-11-12
終了予定日
2027-06-30
目標参加者数
64
試験の種類
介入研究
治験の相・段階
第II相・第二段階
状況
募集中
キーワード
microvessels
oxidative stress
Dulaglutide
Glucagon-like peptide-1
Exercise therapy
主目的
基礎研究
割付方法
無作為化
介入モデル
並行割当
盲検化
三重盲検
群(アーム)/介入
参加グループ/群介入/治療法
プラセボ対照薬Placebo
Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks
プラセボ
Saline placebo
実薬対照薬Dulaglutide
Dulaglutide (0.75 mg/0.5 mL weekly for 2 weeks, then 1.5 mg/0.5 mL weekly for 12 weeks) subcutaneous injection
Dulaglutide
GLP1-RA
実薬対照薬Exercise training
Supervised high intensity interval training on a stationary bicycle will be conducted 3 days per week for 14 weeks. Participants will warm up at low intensity for 3 min then repeat 1-min bouts of 100% peak power output followed by 1-min recovery at 50 W. Training will start with 6 intervals per session, increasing by 2 intervals every 2 weeks. Sessions will end with a 10-min cool-down.
運動トレーニング
supervised high intensity interval training
主要評価項目
評価指標指標の説明時間枠
Microvascular blood volume (MBV)
Insulin mediated change in muscle microvascular blood volume (MBV). A measure of microvascular nitric oxide dependent endothelial function
At baseline and after 14 weeks of treatment.
副次評価項目
評価指標指標の説明時間枠
Brachial artery flow mediated dilation (FMD)
Post-occlusive percent (%) change in diameter. A measure of conduit artery nitric oxide-dependent endothelial function.
At baseline and after 14 weeks of treatment
Glucose infusion rate (GIR)
Mean GIR over the final 30 minutes of euglycemic insulin clamp; a measure of insulin sensitivity
At baseline and after 14 weeks of treatment
Cardiorespiratory fitness, maximum consumption of oxygen (VO2max)
Assessed by cycle ergometer exercise testing.
At baseline and after 14 weeks of treatment
Skeletal muscle oxygenation, deoxyhemoglobin (HHb)
Assessed by frequency domain multi-distance near-infrared spectroscopy (NIRS) monitor at the quadriceps muscle
At baseline and after 14 weeks of treatment. Measured before and after insulin clamp.
適格基準

対象年齢
成人
試験の最低年齢
18 Years
対象性別
全て
  • History of type 1 diabetes, duration > 5 years
  • Age 18-40 years
  • HbA1c < 8.5%
  • BMI 19-34.9 kg/m2
  • Using insulin for diabetes treatment only (multiple daily injections or insulin pump with or without sensor augmentation)
  • On stable regimen of non-diabetic medications for the last 6 months
  • All screening labs within normal limits or not clinically significant
  • C-peptide <0.6 ng/ml

  • Pregnancy or currently breastfeeding
  • Smoking history within 6 months
  • History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) as well as clinically significant cardiac arrhythmias or conduction disorders
  • Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers).
  • Known hypersensitivity to perflutren (contained in Definity© contrast)
  • Screening O2 saturation <90%
  • Musculoskeletal condition preventing participation in exercise testing or exercise training
  • Acute or unstable disease other than T1D
  • Hypoglycemia unawareness (based on Clarke's questionnaire)
  • History of gastroparesis, severe gastroesophageal reflux, pancreatitis, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
  • Anemia (hemoglobin <12 g/dL in women, hemoglobin <13 g/dL in men), eosinophilia (absolute eosinophil count >500 cells/microliter) leukopenia (total white blood cells <4,000 cells/microliter)
  • Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days
  • Hospital admission for DKA within 1 year
責任者
Kaitlin Love, MD, 研究責任者, Principal Investigator, University of Virginia
試験中央連絡先
連絡先: Kaitlin Love, MD, 434-924-9651, [email protected]
連絡先: Lee Hartline, MEd, [email protected]
1 1カ国の場所

Virginia

University of Virginia, Charlottesville, Virginia, 22908, United States
Kaitlin Love, MD, 連絡先, [email protected]
募集中