フィセチンは高齢者の血管機能を改善する
高齢者の血管機能を改善するフィセチンによる老化細胞破壊療法の臨床応用
This is a pilot clinical trial to test the efficacy of intermittent treatment with the flavonoid compound fisetin for improving vascular endothelial function and reducing aortic stiffness in older adults. This trial will also determine the potential mechanisms by which fisetin may improve vascular function, including by decreasing mitochondrial oxidative stress, cellular senescence and senescence-associated secretory phenotype (SASP) factors in circulation. Lastly, safety, tolerability and adherence of fisetin treatment will be assessed.
調査の概要
詳細な説明
Cellular senescence increases with aging and contributes to physiological dysfunction. Studies in animal models show that the flavonoid compound fisetin is an effective treatment for reducing cellular senescence and improving vascular function with aging. No published studies have used fisetin to target cellular senescence in older adults to improve vascular function. In addition, the biological reasons (mechanisms) by which fistin may improve vascular function in older adults has not been assessed. This study will evaluate if intermittent treatment with fisetin in older adults improves vascular function, reduces biological markers of cellular senescence, oxidative stress and inflammatory factors produced by senescent cells (i.e., senescence-associated secretory phenotype factors). The study will also evaluate safety, tolerability and adherence with fisetin treatment.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
-
-
Colorado
-
Boulder、Colorado、アメリカ、80305
- University of Colorado Boulder
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Age 65 years or older
- Women must be postmenopausal
- Body mass index (BMI) <40 kg/m2
- Willing to accept random assignment
- Weight stable in the prior 2 months (<2 kg weight change) and willing to remain weight stable throughout the study
- Ability to understand study procedures and to comply with them for the entire length of the study
- No blood donation within 8 weeks prior to baseline testing; willingness to abstain from blood donation during the study and for 8 weeks after study completion
- Absence of established, serious, unstable, chronic clinical disease (e.g., unstable CVD) as determined by study physician of record based on subject medical history, physical examination, resting ECG and standard clinical blood chemistries
Exclusion Criteria:
- Inability to refrain from alcohol for 24 hours prior to outcome assessment
- Individuals taking fisetin, quercetin, luteolin, Dasatinib, piperlongumine or Navitoclax (supplements or drugs with established senolytic effects) within 6 months prior to baseline testing; should new research reveal other dietary supplements or drugs with potential senolytic effects, their use will be evaluated, and their use may lead to exclusion of the subject by the PI
- New use of regular cardiovascular-acting medication which, in the opinion of the PI, affects the outcomes of the study within 3 months prior to starting baseline testing as reported during medication review during screening (these individuals could be enrolled after 3 months of regular use)
- Chronic use of a dietary supplement which, in the opinion of the PI, affects the outcomes of the study, within 1 month prior to starting baseline testing as reported during medication review during screening (these individuals could be enrolled after 1 month of regular use)
- Active malignancy (including myeloma) or malignancy that was active within 5 years prior to baseline testing
- Inability or unwillingness of individual to give written informed consent
- Current or past participation within 3 months in another clinical trial that, in the opinion of the PI, would affect the outcomes of the study
- Known hypersensitivity or allergy to fisetin
- Blood donation within 2 months prior to baseline testing
- Resting blood pressure >160 mmHg systolic or >110 mmHg diastolic
- Regular vigorous aerobic/endurance exercise
研究計画
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：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Fisetin
Fisetin will be administered in an intermittent manner with two, three-day dosing periods at a dose of 2 mg/kg/day separated by two weeks. |
Fisetin dietary supplement |
|
プラセボコンパレーター：Placebo
Placebo capsules identical in appearance to fistin capsules will be administered in an intermittent manner with two, three-day dosing periods separated by two weeks. |
Placebo capsules identical in appearance to fisetin capsules |
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 endothelial function at 1 month
時間枠：1 month
|
Brachial artery flow-mediated dilation |
1 month
|
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 aortic stiffness at 1 month
時間枠：1 month
|
Carotid-femoral pulse wave velocity |
1 month
|
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 suppression of endothelial function by mitochondrial oxidative stress at 1 month
時間枠：1 month
|
Change in brachial artery flow-mediated dilation with acute, supratherapeutic MitoQ (160mg) |
1 month
|
|
Change from baseline in endothelial cell markers of cellular senescence at 1 month
時間枠：1 month
|
Endothelial cell abundance of p16 and p21 |
1 month
|
|
Change from baseline in blood cell markers of cellular senescence at 1 month
時間枠：1 month
|
p16-positive T-cells |
1 month
|
|
Change from baseline in plasma markers of the senescence-associated secretory phenotype
時間枠：1 month
|
Circulating pro-inflammatory cytokines and chemokines |
1 month
|
協力者と研究者
捜査官
- 主任研究者：Matthew J Rossman, PhD、University of Colorado, Boulder
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 23-0288
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
米国FDA規制機器製品の研究
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。