- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT03520556
Systematic Review and Meta-analysis of the Differential Effects of DHA and EPA on Inflammation
Do Docosahexaenoic and Eicosapentaenoic Acids Have Similar Effects on Inflammation Markers? A Systematic Review and Meta-analysis of Randomized Controlled Trials
Descripción general del estudio
Estado
Descripción detallada
Background: Increased systemic inflammation is positively correlated with the risk for CVD. Among nutritional strategies to prevent and/or reduce chronic inflammation, long-chain omega 3 PUFA (LCn-3PUFA), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have raised tremendous interest for their purported anti-inflammatory effects.
Need for the proposed research: New emerging data from RCTs suggesting distinct effects of DHA and EPA on systemic inflammation calls for a formal analysis of existing data through a systematic review and meta-analysis, which are considered the gold standard of evidence to inform dietary guidelines.
Objective: To conduct a pairwise and network meta-analysis of RCTs in humans to compare the effects of DHA and EPA on surrogate markers of inflammation.
Design: This systematic review and meta-analysis will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and The PRISMA Extension Statement for conducting Network Meta-analyses.
Data sources: MEDLINE, EMBASE and The Cochrane Library will be searched using appropriate search terms.
Study selection: RCTs of ≥7 days duration that have specifically compared the effects of DHA to those of EPA, or RCTs that have assessed the effects of DHA or EPA individually compared with a placebo (control), in which changes in plasma concentration of inflammatory markers, namely C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and adiponectin, were study outcomes. Literature published in languages other than English or French will be not considered.
Data extraction: Titles and abstracts of studies retrieved using the search strategy will be screened independently by two investigators to identify studies that potentially meet the inclusion criteria outlined above. The full text of these potentially eligible studies will be retrieved and independently assessed for eligibility by two investigators with disagreements being resolved by consensus. Extracted information will include: first author's name, publication year, study design, sample size, subject characteristics (for example sex, age, health and body weight status), EPA and DHA doses, EPA and DHA forms, trial duration, composition of the control supplement, inflammation markers studied and the statistical approach for data analysis. Mean ± SEM differences between various treatments will be extracted for all endpoints. Standard computations and imputations will be used to derive missing variance data. Risk of bias will be assessed using the Cochrane Risk of Bias Tool. The overall quality and strength of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Risk of bias for network meta-analysis will incorporate assessment of transitivity.
Outcomes: Four outcomes will be assessed: 1) plasma CRP 2) plasma IL-6, 3) plasma TNF-alpha and 4) plasma adiponectin.
Data synthesis: We will use standard Cochrane methods for pairwise meta-analysis and augment this evidence using network meta-analysis methods. Mean differences will be pooled for direct comparisons (DHA vs. EPA) using DerSimonian and Laird random-effects model will be used even in the absence of statistically significant between-study heterogeneity, as they yield more conservative summary effect estimates in the presence of residual heterogeneity. We will present the pooled estimates as mean differences and 95% confidence intervals. We will perform a frequentist network meta-analysis using multivariate meta-analysis model using 'network' suite of commands available in STATA. Mean differences will be pooled for direct comparisons (DHA vs. EPA) and indirect comparisons (DHA vs. placebo and EPA vs. placebo using placebo as the common comparator). We will present the contribution of direct and indirect evidence to mixed evidence using contribution plots. Assumption of consistency will be tested using design-by-treatment model. Paired analyses will be applied for crossover trials. Heterogeneity will be assessed by the Cochran Q statistic and quantified by the I2. To explore sources of heterogeneity, we will conduct sensitivity analyses, in which each study is systematically removed. If there are more than 10 studies, we will also explore sources of heterogeneity using meta-regression analyses and a priori defined subgroup analyses such as body weight status (normal-weight, overweight, obese), health status (for example diabetes, CVD), age, sex, dose, baseline measurements for each outcome, study design (parallel, crossover), study duration, risk of bias, and individual domains of risk of bias. Meta-regression analyses will assess the significance of categorical and continuous subgroup analyses. When more than 10 studies are available, publication bias will be investigated by inspection of funnel plots and formal testing using the Egger test and the Begg test. If publication bias is suspected, we will attempt to adjust for funnel plot asymmetry by imputing the missing study data using the Duval and Tweedie trim and fill method.
Knowledge translation plan: Results from this systematic review and meta-analysis will be disseminated through traditional means such as interactive presentations at local, national, and international scientific meetings and publication in high impact factor journals. Target audiences will include the public health and scientific communities with interest in nutrition, inflammation, and CVD.
Significance: The findings generated by this analysis will provide invaluable and timely comparative information on the specific efficacy of DHA and EPA as one of the key nutritional modalities for the treatment of chronic inflammation in high-risk men and women. This is important considering that LCn-3PUFA supplements are increasingly being used by the population and an ever growing market in the dietary supplements' industry.
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Quebec, Canadá, G1V 0A6
- Institute of Nutrition and Functional Foods (INAF)
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Randomized controlled trials of ≥7 days duration in humans
- Suitable control (i.e. fatty acids other than EPA and DHA as control)
- Adults (18 years old and older)
- Viable outcome data
Exclusion Criteria:
- Non-human studies
- Non-randomized treatment allocation
- Randomized controlled trials of <7 days duration
- Lack of a suitable control
- Children
- No viable outcome data
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
---|
docosahexaenoic acid (DHA)
Adults supplemented with DHA in a randomized controlled trial of ≥7 days duration
|
eicosapentaenoic acid (EPA)
Adults supplemented with EPA in a randomized controlled trial of ≥7 days duration
|
control
Adults supplemented with control fatty acids in a randomized controlled trial of ≥7 days duration assessing the effects of EPA and/or DHA
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Change in plasma concentration of CRP
Periodo de tiempo: Baseline and up to 5 years
|
Change in fasting plasma concentration of CRP with DHA vs. EPA or DHA vs. control or EPA vs. control
|
Baseline and up to 5 years
|
Change in plasma concentration of IL-6
Periodo de tiempo: Baseline and up to 5 years
|
Change in fasting plasma concentration of IL-6 with DHA vs. EPA or DHA vs. control or EPA vs. control
|
Baseline and up to 5 years
|
Change in plasma concentration of TNF-alpha
Periodo de tiempo: Baseline and up to 5 years
|
Change in fasting plasma concentration of TNF-alpha with DHA vs. EPA or DHA vs. control or EPA vs. control
|
Baseline and up to 5 years
|
Change in plasma concentration of adiponectin
Periodo de tiempo: Baseline and up to 5 years
|
Change in fasting plasma concentration of adiponectin with DHA vs. EPA or DHA vs. control or EPA vs. control
|
Baseline and up to 5 years
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
Publicaciones Generales
- Vors C, Allaire J, Mejia SB, Khan TA, Sievenpiper JL, Lamarche B. Comparing the Effects of Docosahexaenoic and Eicosapentaenoic Acids on Inflammation Markers Using Pairwise and Network Meta-Analyses of Randomized Controlled Trials. Adv Nutr. 2021 Feb 1;12(1):128-140. doi: 10.1093/advances/nmaa086.
- Vors C, Allaire J, Blanco Mejia S, Khan TA, Sievenpiper JL, Lamarche B. Reply to J Morze and L Schwingshackl. Adv Nutr. 2021 Feb 1;12(1):278-279. doi: 10.1093/advances/nmaa131. No abstract available.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- SRMA-EPA-DHA-INFL
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.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Enfermedades cardiovasculares
-
Mayo ClinicInscripción por invitaciónRiesgo cardiovascular | Prevención cardiovascularEstados Unidos
-
University of DelawareReclutamientoFactor de riesgo cardiovascular | Salud cardiovascularEstados Unidos
-
Oregon Health and Science UniversityTerminadoEnfermedad cardiovascular | Factores de riesgo cardiovascularEstados Unidos
-
Medical College of WisconsinReclutamientoEnfermedades cardiovasculares | Factor de riesgo cardiovascular | Salud cardiovascularEstados Unidos
-
Hospital Mutua de TerrassaTerminadoEnfermedad cardiovascular | Factor de riesgo cardiovascularEspaña
-
University of FloridaUniversity of Alabama at Birmingham; Brown UniversityTerminadoEnfermedad cardiovascular | Influencia psicosocial en la enfermedad cardiovascularEstados Unidos
-
Medical College of WisconsinTerminadoEnfermedades cardiovasculares | Factores de riesgo cardiovascular | Salud cardiovascular | Impacto del cantoEstados Unidos
-
Centre Hospitalier Universitaire DijonTerminadoPacientes de Alto Riesgo Cardiovascular | Pacientes de bajo riesgo cardiovascularFrancia
-
Shanghai 10th People's HospitalDesconocidoPresión arterial | Factor de riesgo cardiovascular | Mortalidad global | Mortalidad cardiovascular | Eventos cardiovasculares | Daño al órgano dianaPorcelana
-
Methodist Health SystemTerminado