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.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Janosch Niknam-Saeidi, MD
- Correo electrónico: janosch.niknamsaeidi@meduniwien.ac.at
Copia de seguridad de contactos de estudio
- Nombre: Manfred Hecking, MD, PhD
- Correo electrónico: manfred.hecking@meduniwien.ac.at
Ubicaciones de estudio
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State of Vienna
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Vienna, State of Vienna, Austria, 1090
- Chronic Hemodialysis Unit, Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
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Contacto:
- Janosch Niknam-Saeidi, MD
- Correo electrónico: janosch.niknamsaeidi@meduniwien.ac.at
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Sub-Investigador:
- Janosch Niknam-Saeidi, MD
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: 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.
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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
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Experimental: 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).
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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
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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Cholesterol Efflux Capacity (CEC)
Periodo de tiempo: Weeks 1, 8, and 16
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Cholesterol efflux capacity of apolipoprotein B-depleted serum, measured with a cell-based fluorescent assay and reported as percentage cholesterol efflux (%).
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Weeks 1, 8, and 16
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Serum Amyloid A (SAA)
Periodo de tiempo: Weeks 1, 8, and 16
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Serum amyloid A concentration in serum, obtained from routine clinical laboratory measurement and reported in mg/L.
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Weeks 1, 8, and 16
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Biologically Effective HDL
Periodo de tiempo: Weeks 1, 8, and 16
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Biologically effective HDL, calculated from concomitantly measured HDL cholesterol and serum amyloid A concentrations and reported in mg/dL.
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Weeks 1, 8, and 16
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Procesos Patológicos
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedad crónica
- Atributos de la enfermedad
- Insuficiencia renal
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades cardiovasculares
- Insuficiencia Renal Crónica
- Ácidos grasos
- Lípidos
- Ácidos grasos, insaturados
- Aceites
- Grasas dietéticas
- Grasas
- Grasas dietéticas, insaturadas
- Aceites de pescado
- Ácidos grasos, omega-3
Otros números de identificación del estudio
Otros números de identificación del estudio
- EK Nr: 1072/202 (EFFLUX-HD)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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