Effect of 4 Weeks of Oral Probiotic Desulfovibrio Piger Supplementation on Immunological and Metabolic Parameters in Individuals With Longstanding Type 1 Diabetes (PROSPER)
調査の概要
詳細な説明
The investigators perform a double-blind, randomized, placebo-controlled trial with two arms (10 participants per arm, total of 20 participants) in adults with longstanding type 1 diabetes with residual beta cell function. The study duration is 6 weeks, with 4 weeks of intervention in which participants will be given D. piger or placebo once daily and 2 weeks of washout period. The main study enpoints include the changes (versus baseline) in parameters of systemic/intestinal inflammation and beta cell function between the placebo and D.piger-treatment arms at the end of treatment (4 weeks). In addition, any long-lasting effects will be determined by assessing the changes in the above described markers after a 2 week washout period (6 weeks).
Secondary endpoints include glucose variability (continuous glucose monitoring, CGM), fecal microbiome composition (including strain engraftment of D. piger, plasma metabolites), immune cell phenotype and frequency and validated questionnaires (gastro-intestinal complaints) at these three timepoints (0,4,6 weeks).
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Max Nieuwdorp, Prof. Dr.
- 電話番号：+31 20-5669111
- メール：m.nieuwdorp@amsterdamumc.nl
研究場所
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-
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Amsterdam、オランダ、1105 AZ
- 募集
- Amsterdam UMC
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コンタクト：
- Max Nieuwdorp, Prof. Dr.
- 電話番号：+31 20-5669111
- メール：m.nieuwdorp@amsterdamumc.nl
-
Amsterdam、オランダ、1066 EC
- 募集
- Diabeter Centrum Amsterdam
-
コンタクト：
- Max Nieuwdorp, Prof. Dr.
- 電話番号：+31 20-5669111
- メール：m.nieuwdorp@amsterdamumc.nl
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Males or females, age >18 years
- A diagnosis of type 1 diabetes, with duration of more than 5 years, with minimally one of antiGAD65, IA2, ZnT8 autoantibodies present assessed at diagnosis or routine visits at Diabeter Centrum.
- Evidence of remaining residual beta cell function with detectable UCPCR (more than 0.01 nmol/mmol C-peptide/creatinine ratio) and or fasting plasma C-peptide more than 0.2 mmol/L.
- BMI 18-30 kg/m2
Exclusion Criteria:
- Use of antibiotics or proton-pump inhibitors within the last three months before screening or during study period
- Use of other probiotic supplementation within the last month before screening or during study period
- A history of cholecystectomy
- Overt untreated gastrointestinal disease, inflammatory bowel disease or abnormal bowel habits
- Absence of a large bowel (ie colostomy)
- Evidence for comprised immunity (HIV infection, chemotherapy, other autoimmune diseases, systemic anti-inflammatory therapy)
- History of cardiovascular disaeses (CVD) events
- Hepatic enzymes>2.5 higher than the upper limit of normal range, determined during MARVEL visits/routine visits
- Kidney failure (eGFR <15ml.min/1.73m2), dialysis, kidney transplantation,
- Inability or unwillingness to donate feces or urine.
- Smoking or illicit drug use (e.g. MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
- Alcohol abuse (equal or above 21 units per week)
- Inability or unwillingness to provide informed consent.
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 |
|---|---|
|
実験的：Probiotic Desulfovibrio piger
Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)
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Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)
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|
プラセボコンパレーター：Placebo
placebo (10ml PBS containing 10% glycerol and 10% maltodextrin)
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Placebo (10ml PBS containing 10% glycerol and 10% maltodextrin)
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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 |
|---|---|---|
|
Parameters of systemic and intestinal inflammation
時間枠：From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
|
systemic inflammation determined by measuring plasma CRP, and proinflammatory cytokines (IFNgamma, IFN alpha, TNFalpha) intestinal inflammation assessed by LB, iFABP, zonulin in plasma |
From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
|
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Residual beta cell function
時間枠：From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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Assessed by C peptide AUC during mixed meal tolerance test and/or post meal urine C-peptide/creatinine ratio levels.
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From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Glucose variability
時間枠：From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
|
percentage time in euglycemic range, time above range, time below range and glucose variability measured by continuous glucose monitoring (CGM)
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From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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Immune cell phenotypes and frequency
時間枠：From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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Immunophenotyping by flow cytometry of PBMC (peripheral blood mononuclear cells) to determine frequency of T cell subsets with activation/exhaustion marker expression
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From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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Fecal microbiome composition and strain engraftment
時間枠：From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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using 16s rRNA sequencing, primer-specific quantitative PCR for D. piger detection in feces and plasma metabolites
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From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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Gastrointestinal Symptom Rating Scale (GSRS)
時間枠：From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
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Questionnaire.
The minimum and maximum score are 15 and 105 points respectively, and a higher score in the scale reflects more gastro-intestinal complaints.
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From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
|
協力者と研究者
捜査官
- 主任研究者：Max Nieuwdorp, Prof. Dr.、Amsterdam UMC
研究記録日
主要日程の研究
研究開始 (推定)
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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