Fish Oil and HDL Function in Patients on Maintenance Hemodialysis (EFFLUX-HD)
Mechanistic Effects of n-3 Polyunsaturated Fatty Acid Supplementation on HDL Function in Patients Receiving Maintenance Hemodialysis (EFFLUX-HD): Study Protocol for a Randomized, Open-label, Crossover Trial
Patients who receive maintenance hemodialysis have a very high risk of cardiovascular disease, and standard cholesterol-lowering treatments such as statins have not been shown to reduce cardiovascular events in this group. A recent clinical trial (PISCES) found that high-dose omega-3 fatty acids (fish oil) reduced cardiovascular events in hemodialysis patients, but the reason for this benefit is not understood.
One possible explanation is that, in kidney failure, high-density lipoprotein (HDL) no longer works normally. This study investigates whether omega-3 fatty acid supplementation improves the function of HDL in people on maintenance hemodialysis.
Forty adults on maintenance hemodialysis will take part. Each participant receives fish oil (4 g per day) for 8 weeks and also has an 8-week period without supplementation; participants are randomly assigned to the order of these two periods (crossover design), for a total of 16 weeks each. The main measure is cholesterol efflux capacity, a laboratory test of how well HDL removes cholesterol from cells. The study also examines other markers of HDL quality.
This is an exploratory, mechanistic study. Its aim is to determine whether omega-3 fatty acids change HDL function and to inform the design of larger future trials.
調査の概要
詳細な説明
Patients receiving maintenance hemodialysis (HD) experience exceptionally high cardiovascular (CV) mortality that is not adequately addressed by conventional lipid-lowering strategies. The PISCES trial demonstrated that high-dose n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation reduces CV events in HD patients, yet the underlying mechanism remains unknown.
In the uremic milieu, HDL undergoes qualitative changes-including enrichment with serum amyloid A (SAA), loss of anti-oxidative capacity, and impaired cholesterol efflux capacity (CEC)-that render it dysfunctional and may contribute to CV risk independently of HDL cholesterol concentration. Evidence from non-dialysis populations suggests that n-3 PUFA can favorably modify the HDL proteome and improve HDL function. The investigators hypothesize that n-3 PUFA supplementation favorably modulates HDL function in HD patients, which could help explain the CV benefit observed in PISCES.
EFFLUX-HD is a single-center, prospective, randomized, open-label, crossover, exploratory mechanistic study conducted at the Chronic Hemodialysis Unit of the Vienna General Hospital (Medical University of Vienna). Forty adults on maintenance HD are randomized 1:1 to one of two treatment sequences that differ in the order of an 8-week n-3 PUFA supplementation period (4 g/day fish oil; approximately 1.6 g EPA and 0.8 g DHA, matching the PISCES dose) and an 8-week off-treatment period, without a formal washout, for a total of 16 weeks per participant. The crossover design allows each participant to serve as their own control, removing the substantial between-participant variability in HDL functional measures.
Outcomes are analyzed using linear mixed-effects models. No formal sample-size calculation was performed given the exploratory, mechanistic design; the target of 40 participants is intended to estimate within-participant effects and the variability of HDL functional parameters to inform future confirmatory trials. The study was approved by the Ethics Committee of the Medical University of Vienna and is conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice.
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：Janosch Niknam-Saeidi, MD
- メール：janosch.niknamsaeidi@meduniwien.ac.at
研究連絡先のバックアップ
- 名前：Manfred Hecking, MD, PhD
- メール：manfred.hecking@meduniwien.ac.at
研究場所
-
-
State of Vienna
-
Vienna、State of Vienna、オーストリア、1090
- Chronic Hemodialysis Unit, Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
-
コンタクト：
- Janosch Niknam-Saeidi, MD
- メール：janosch.niknamsaeidi@meduniwien.ac.at
-
副調査官：
- Janosch Niknam-Saeidi, MD
-
-
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:
- age ≥ 18 years
- receiving maintenance in-center hemodialysis
- able to provide written informed consent
- clinically stable condition (no hospitalization within 4 weeks prior to baseline)
Exclusion Criteria:
- inability or unwillingness to provide informed consent
- known hypersensitivity or intolerance to fish oil or n-3 PUFA-containing products
- use of n-3 PUFA supplements at baseline or within the preceding 8 weeks
- pregnancy
- acute infection, hospitalization or major inflammatory condition at the time of baseline assessment
- any condition that, in the investigator's opinion, would make participation unsafe or interfere with study participation or data interpretation
- inherited lipid metabolism disorders
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：防止
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Group A: n-3 PUFA then off-treatment
Participants receive n-3 PUFA supplementation (4 g/day fish oil) for 8 weeks, followed by an 8-week off-treatment period.
|
4g/day fish oil (four 1 g capsules) providing approximately 1.6 g EPA and 0.8 g DHA, taken for 8 weeks, matching the PISCES dose
|
|
実験的：Group B: off-treatment then n-3 PUFA
Participants undergo an 8-week off-treatment period, followed by 8 weeks of n-3 PUFA supplementation (4 g/day fish oil).
|
4g/day fish oil (four 1 g capsules) providing approximately 1.6 g EPA and 0.8 g DHA, taken for 8 weeks, matching the PISCES dose
|
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 |
|---|---|---|
|
Cholesterol Efflux Capacity (CEC)
時間枠：Weeks 1, 8, and 16
|
Cholesterol efflux capacity of apolipoprotein B-depleted serum, measured with a cell-based fluorescent assay and reported as percentage cholesterol efflux (%).
|
Weeks 1, 8, and 16
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Serum Amyloid A (SAA)
時間枠：Weeks 1, 8, and 16
|
Serum amyloid A concentration in serum, obtained from routine clinical laboratory measurement and reported in mg/L.
|
Weeks 1, 8, and 16
|
|
Biologically Effective HDL
時間枠：Weeks 1, 8, and 16
|
Biologically effective HDL, calculated from concomitantly measured HDL cholesterol and serum amyloid A concentrations and reported in mg/dL.
|
Weeks 1, 8, and 16
|
協力者と研究者
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
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
- EK Nr: 1072/202 (EFFLUX-HD)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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
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