糖尿病患者の皮膚潰瘍の創傷治癒に対する個別栄養介入の評価
糖尿病患者の皮膚潰瘍の再生能力と創傷治癒に対する MSC 由来のエキソソームの適用と合わせた個別化された栄養介入の評価
The ageing population and the increase in diabetes raise the prevalence of chronic skin ulcers (CCU). In diabetics, precursor cell mobilization decreases. In wounds, the inflammation is prolonged and oxidative stress increases. This is an unfavorable microenvironment for healing. A major risk factor in the development of CCU is nutritional deficiency. Healing needs energy and nutrients for regeneration. In diabetics the malnutrition can be more than 60%. However, although the provision of certain nutrients can improve the healing capacity, it is not a common clinical practice to nutritionally evaluate diabetic with CCU. Exosomes are extracellular vesicles that reflect the physiological state of the cells producing them. Stem cell derivatives exosomes are rich in factors, that can provide a favorable microenvironment for tissue regeneration.
The aim of this project is to develop a therapeutic process to accelerate the healing of diabetic CCU, based on the correction of nutritional deficiencies, to improve the regenerative capacity, together with the application of exosomes from mesenchymal stem-cell (MSC) in the wound, creating a microenvironment that favors tissue regeneration. For this, a pilot clinical trial with diabetic patients with CCU is proposed, to evaluate the effect of personalized nutritional supplementation on healing and regenerative capacity.
調査の概要
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究場所
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Andalusia
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Córdoba、Andalusia、スペイン、14004
- Hospital Universitario Reina Sofía de Córdoba
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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:
- Signature of the informed consent
- Age between 50 and 80 years
- Diagnosis of Diabetes Mellitus for more than 1 year
- Documented diagnosis of peripheral artery disease
- HbA1c < 9%
- Category 5 in the Rutherford-Becker classification
Exclusion Criteria:
- Poor cognitive function, dementia or psychiatric conditions
- Osteomyelitis, gangrene, malignancy or immunocompromised disease
- Thromboangiitis obliterans or Buerger's disease
- Clinical evidence of invasive infection in the target limb requiring IV antibiotherapy
- Presence of neuropathic ulcers only
- Human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) positive.
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：階乗代入
- 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 |
|---|---|
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実験的：Nutritional Intervention (NI)
In addition to the usual treatment, will receive dietary advice and a nutritional supplement, according to the results of their evaluation in the Endocrinology Service |
Those with malnutrition criteria will also receive a nutritional supplement (e.g. fortimel cubitan, advanced or extra, Nutricia) or another of similar composition, in case of intolerance to the first option. The aim will be to provide at least 50% of the recommended intakes for the main nutrients related to wound healing. |
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介入なし：Control (C)
Who will continue with their usual treatments in the Diabetic Foot Unit and they will receive dietary advice |
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 |
|---|---|---|
|
Ulcer evaluation
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in size ulcer assessed by picture, including ruler to measure their size |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Composite measure of markers of nutritional status
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
Change from baseline in nutritional status assessed from blood samples |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Composite measure of haemogram
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in haemogram assessed from blood samples |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Hemoglobin A1c (HbA1c) Test for Diabetes
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in HbA1c (%) assessed from blood samples |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Measure of markers of nutritional status, include to thyrotropin
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
Change from baseline in thyrotropin (mlU/L) assessed from blood samples |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
|
Ultrasensitive C-reactive Protein (CRP) test
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in CRP (mg/L) assessed from blood samples |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Quantification of circulating endothelial progenitor cells (EPC)
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in total CD34+ or CD133+ cells expressing vascular endothelial growth factor receptor 2 (VEGFR2) analyzed by flow cytometry |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Concentration of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor A (VEGFA)
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in concentration of SDF-1 and VEGFA factors in serum by ELISA |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Nutritional Risk
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in nutritional risk assessed by Malnutrition Universal Screening Tool (MUST) |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Diagnosis of malnutrition
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in diagnosis of malnutrition assessed by Global Leadership Initiative on malnutrition (GLIM criteria) |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Sarcopenia
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in sarcopenia assessed by SARC-F |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Handgrip Strength
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in handgrip strength assessed by dynamometry |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Body weight and height
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Body weight and height will be combined to report body mass index (BMI) in kg/m^2. Change from baseline in BMI |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Tricipital skinfold
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in tricipital skinfold using a skinfold caliper |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Arm circumference
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in arm circumference in centimeters (cm) |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Waist and hip circumferences
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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waist and hip circumferences (cm) will be combined to report Waist and Hip Ratio (WHR). Change from baseline in WHR |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Body Fat
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in body fat assessed by multifrequency bioimpedaciometry and bioelectrical impedance vector analysis |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
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Muscle Mass
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in muscle mass assessed by multifrequency bioimpedaciometry and bioelectrical impedance vector analysis |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Hydration status
時間枠：Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
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Change from baseline in hydration status assessed by multifrequency bioimpedaciometry and bioelectrical impedance vector analysis |
Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation
|
協力者と研究者
捜査官
- 主任研究者：Antonio Casado-Díaz, PhD、Maimonides Biomedical Research Institute of Cordoba
- 主任研究者：Alfonso Calañas, PhD、Hospital General Universitario Reina Sofía de Murcia
出版物と役立つリンク
一般刊行物
- Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, Baptista G, Barazzoni R, Blaauw R, Coats A, Crivelli A, Evans DC, Gramlich L, Fuchs-Tarlovsky V, Keller H, Llido L, Malone A, Mogensen KM, Morley JE, Muscaritoli M, Nyulasi I, Pirlich M, Pisprasert V, de van der Schueren MAE, Siltharm S, Singer P, Tappenden K, Velasco N, Waitzberg D, Yamwong P, Yu J, Van Gossum A, Compher C; GLIM Core Leadership Committee; GLIM Working Group. GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community. Clin Nutr. 2019 Feb;38(1):1-9. doi: 10.1016/j.clnu.2018.08.002. Epub 2018 Sep 3.
- Malmstrom TK, Morley JE. SARC-F: a simple questionnaire to rapidly diagnose sarcopenia. J Am Med Dir Assoc. 2013 Aug;14(8):531-2. doi: 10.1016/j.jamda.2013.05.018. Epub 2013 Jun 25. No abstract available.
- Armstrong DG, Hanft JR, Driver VR, Smith AP, Lazaro-Martinez JL, Reyzelman AM, Furst GJ, Vayser DJ, Cervantes HL, Snyder RJ, Moore MF, May PE, Nelson JL, Baggs GE, Voss AC; Diabetic Foot Nutrition Study Group. Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial. Diabet Med. 2014 Sep;31(9):1069-77. doi: 10.1111/dme.12509. Epub 2014 Jun 19.
- Basiri R, Spicer MT, Levenson CW, Ormsbee MJ, Ledermann T, Arjmandi BH. Nutritional Supplementation Concurrent with Nutrition Education Accelerates the Wound Healing Process in Patients with Diabetic Foot Ulcers. Biomedicines. 2020 Aug 3;8(8):263. doi: 10.3390/biomedicines8080263.
- Haughey L, Barbul A. Nutrition and Lower Extremity Ulcers: Causality and/or Treatment. Int J Low Extrem Wounds. 2017 Dec;16(4):238-243. doi: 10.1177/1534734617737639. Epub 2017 Nov 16.
- Kurian SJ, Miraj SS, Benson R, Munisamy M, Saravu K, Rodrigues GS, Rao M. Vitamin D Supplementation in Diabetic Foot Ulcers: A Current Perspective. Curr Diabetes Rev. 2021;17(4):512-521. doi: 10.2174/1573399816999201012195735.
- Zhang SS, Tang ZY, Fang P, Qian HJ, Xu L, Ning G. Nutritional status deteriorates as the severity of diabetic foot ulcers increases and independently associates with prognosis. Exp Ther Med. 2013 Jan;5(1):215-222. doi: 10.3892/etm.2012.780. Epub 2012 Oct 30.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
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
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