マイクロバイオータ媒介フラボノイド代謝物による認知健康 (MAEVE)
MAEVE：認知機能の健康のためのマイクロバイオータ媒介フラボノイド代謝物
Globally, populations are ageing increasing the prevalence of Alzheimer's disease (AD), due to lack of effective treatments. The traditional Mediterranean diet, rich in fibre and polyphenols (PPs) can help prevent or delay cognitive dysfunction and preserve healthy brain structure and function. Cognitive decline is inversely associated with higher PP intakes (>421mg/day) i.e., total flavonoids, flavan-3-ols and flavonoid oligomers. The positive brain effects of flavonoid intake are likely mediated in part by gut microbial PP metabolites, consistent with the emerging role of the brain-gut microbiome (BGM) system in neurodegeneration. Our preliminary data indicate that circulating phenyl-γ-valerolactones (PVL), neuroprotective compounds exclusively produced by gut microbiota from flavan-3-ol rich foods18 are associated with delaying cognitive dysfunction. Intake of PPs change gut microbial composition and function, altering the physiology of the host's secondary bile acid (BA) pool through modulation of bacterial 7α-dehydroxylation of de-conjugated primary BAs into secondary BAs. This is noteworthy as 7α-dehydroxylation of BAs does not happen in the brain and because gut microbial BA metabolites have regulatory and signalling functions in the brain. The ratio between certain primary and secondary BAs is also dysregulated in AD with significantly lower serum concentrations of cholic acid (a primary BA) and increased levels of deoxycholic acid (a bacterially produced secondary BA). The increased ratio of cholic acid to deoxycholic acid is correlated with cognitive decline. Increased levels of tyrosine, tryptophan, purine, and tocopherol have also been identified in postmortem AD brains. However, specific pathways and mechanisms underlying these associations are unclear. In this multi-PI application by leaders in the field of BGM interactions, we leverage the collectively (NIH, HSC, SFI) funded Tripartite US-Ireland R&D Partnership Program to determine the mechanisms involved in PP intake on maintaining healthier cognitive and brain function, as mediated by gut microbiota metabolites of PP and BAs in 50+ year old elderly with enhanced AD risk.
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
研究連絡先
- 名前：Chris Gill, PhD
- 電話番号：+44 28 7012 3181
- メール：c.gill@ulster.ac.uk
研究連絡先のバックアップ
- 名前：Aoife Caffrey, PhD
- 電話番号：+44 (0) 28 701 23401
- メール：a.caffrey@ulster.ac.uk
研究場所
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Coleraine、イギリス、BT52 1SA
- 募集
- Ulster University, Human Intervention Studies Unit
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コンタクト：
- Aoife Caffrey, PhD
- 電話番号：+44 (0) 28 701 23401
- メール：a.caffrey@ulster.ac.uk
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コンタクト：
-
主任研究者：
- Chris Gill, PhD
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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:
- 50+ years
- BMI ≥ 25 kg/m2
- Enhanced risk of AD - defined as family history of AD, 1st degree family member
- Habitually consume suboptimal diets such as typical Western diet (i.e., high in animal products, refined carbohydrates and processed food).
- Subjects capable of and willing to comply with the protocol and to give their written informed consent.
Exclusion Criteria:
- Cognitive impairment at time of recruitment into the study, as measured by the Mini Mental Status Exam (MMSE, score 25-30), and Clinical Dementia Rating (CDR, score=0) or Everyday Cognition Scale-12 (ECog-12, score<1.36 included).
- Pre-existing psychosis or psychiatric conditions.
- Currently receiving treatment for dementia.
- History of substance abuse or cerebrovascular events.
- Heavy use of tobacco (>1/2 pack per day)
- Any intolerance or allergy documented or suspected to one of the components of the study products.
- Have taken probiotics or antibiotic therapy within the last 1 month
- Change in medication use in the last 3 months.
- Frailty, malnutrition, or food allergy/intolerance requiring special diets will also be excluded.
- Following any specific diet (vegetarian, vegan, etc.)
- Body weight at enrolment greater than 400lbs due to weight restrictions on the MRI table.
- Pregnant, breastfeeding, postpartum for less than 6 months, or unwilling to practice birth control during participation in the study.
- Unable to safely participate in the MRI (claustrophobia, presence of devices affected by MRI such as pacemakers, neurostimulators, or metallic foreign body, etc.)
- Chronic pain.
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Having a psychological or linguistic inability to sign the informed consent;
- Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision;
- Subject participating in another biomedical study or participation in another study within the 3 months before entry into this study.
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：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：プラセボサプリメント
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Micronutrient matched placebo |
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実験的：Polyphenol Supplement
Juice Plus Essentials, Berry Blend Capsules |
Juice Plus Essentials, Berry Blend 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 |
|---|---|---|
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Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - stool
時間枠：Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12)
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Measurement of metabolomics via stool specimen. |
Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12)
|
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Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - blood
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Measurement of metabolomics via blood specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
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Differences in microbiome levels pre, mid, & post intervention - Stool
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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16S RNA sequencing to measure microbiome levels via stool specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
|
Differences in microbiome levels pre & post intervention - Blood
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
16S RNA sequencing to measure microbiome levels via blood specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
|
Differences in microbiome levels pre, mid, & post intervention - Stool
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
|
Differences in microbiome levels pre, mid, & post intervention - Blood
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
|
Differences in Cognitive Measures pre, mid, & post intervention - Executive Function
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Administration of a standardized Stroop Neuro-psychological test; participants ability to correctly identify colours when words are printed in conflicting ink colours. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Differences in Cognitive Measures pre, mid, & post intervention - Executive Function
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Administration of a standardized Trails A & B; participants ability to connect dots, in order, as quickly as possible. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Differences in Cognitive Measures pre, mid, & post intervention
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Differences in Cognitive Measures pre, mid, & post intervention
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Administration of a standardized arithmetic task; participants ability to complete quick mental math. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Differences in tryptophan-associated metabolite profiles pre, mid, and post intervention - Stool
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
|
Measurement of tryptophan-associate metabolite profiles via stool specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Differences in Bile Acid's (BA's) pre, mid, & post intervention - Stool
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Measurement of BA's via stool specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Differences in Inflammatory markers pre, mid, & post intervention - Blood
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Measurement of inflammatory markers via blood specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Differences in Alzheimer's Disease (AD) markers pre, mid, & post intervention - Blood [Time
時間枠：Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Measurement of AD markers via blood specimen. |
Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12).
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Anthropometrics - BMI
時間枠：Measured three times, once at each in-clinic appointment (week 0, month 6, month 12)
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Measurement of height(in) and weight(lbs), used to calculate body mass index (BMI) |
Measured three times, once at each in-clinic appointment (week 0, month 6, month 12)
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Questionnaire Data
時間枠：Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
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Use of validated surveys to assess ingestive behaviours, social isolation, stress, health, physical activity, etc., self-reported by the participant at home. |
Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
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Monthly Questionnaire Data
時間枠：Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
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Collected once a month for the duration of the study (12months). |
Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
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Anthropometrics - waist and hip circumference
時間枠：Measured three times, once at each in-clinic appointment (week 0, month 6, & month 12)
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Measurement of waist and hip circumference (cm) |
Measured three times, once at each in-clinic appointment (week 0, month 6, & month 12)
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Systolic and Diastolic Blood Pressure
時間枠：Measured three times, once at each in-clinic appointment (week 0, month 6, month 12).
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Measurement of the pressure of circulating blood at rest |
Measured three times, once at each in-clinic appointment (week 0, month 6, month 12).
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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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Differences in Multimodal Brain Signatures pre, mid, & post intervention
時間枠：Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit.
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Neuroimaging of participants brain via magnetic resonance imaging (MRI) procedure. |
Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit.
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Chris Gill, PhD、Ulster University, Human Intervention Studies Unit, Coleraine, Co. Londonderry, BT52 1SA, United Kingdom.
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
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。