Pomegranate Dietary Supplements in AUD and ALD
Supplementation of Pomegranate Dietary Supplements and Characterization of Urolithin Metabotypes in Patients With Alcohol Use Disorder (AUD) and Alcohol-associated Liver Disease (ALD)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
A large body of anecdotal evidence suggests beneficial effects for many botanical dietary supplements (BDS) on human health. The U.S. alone spent ~$7.5 billion on BDS in 2016, suggesting significant interest in the consumption of such products. Since ancient times, pomegranate has been known as a 'healing food', with numerous health benefits, including prevention of health risk factors for high blood pressure, arthritis, high cholesterol, oxidative stress, and hyperglycemia (1-4). Despite reported benefits from consumption of pomegranate dietary supplements (PDS), the overall outcomes of clinical trials were not uniform, and the results were inconclusive (5-7). However, gut microbial metabolites derived from polyphenolics of pomegranate have been shown to promote many beneficial activities, including anti-oxidative and anti-inflammatory activities (8- 12). Thus, the inter-individual variation in human gut microbiota compositions and their metabolic capacities may hamper the predicted PDS-mediated benefits. We postulate that harboring the specific gut microbiota responsible for metabolizing PDS into beneficial metabolites is critical to manifesting the complete benefits of PDS consumption. Recently, we reported one such microbial metabolite, 'urolithin A' (UroA), derived from ellagic acid-rich diets (e.g., pomegranate), significantly enhanced gut barrier function in addition to blocking unwarranted inflammation in colitis models (13) and protected from alcoholic liver disease (ALD) in mouse models (unpublished data). UroA is produced only in 40-50% of humans, who harbor the appropriate microbiota capable of converting consumed ellagic acid-rich diets (such as pomegranates, berries, and walnuts). UroA levels varied significantly among populations, to micromolar levels in some individuals. The direct correlations between UroA levels and human health/disease conditions are not yet available.
This project aims to determine an individual's ability to generate active gut microbial metabolites called urolithins upon consumption of pomegranate dietary supplements. We, and others, reported that urolithins are the major active metabolites that are responsible for the beneficial activities that are rendered from eating pomegranates, berries, or walnuts. However, the production of urolithins from the parent compound ellagic acid (EA) is dependent upon the presence of certain bacteria in the human gut. In this trial, we propose to investigate variations in gut microbiota and their capacity to metabolize pomegranate dietary supplements (PDS) into active urolithins. We will measure the levels of urolithins in blood as well as inflammatory cytokines in plasma samples upon consumption of PDS.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Vatsalya Vatsalya, MD
- Número de teléfono: 502-852-8928
- Correo electrónico: v0vats01@louisville.edu
Copia de seguridad de contactos de estudio
- Nombre: Venkatakrishna R Jala, PhD
- Número de teléfono: 502-852-5523
- Correo electrónico: jvrao001@louisville.edu
Ubicaciones de estudio
-
-
Kentucky
-
Louisville, Kentucky, Estados Unidos, 40202
- University of Louisville
-
Investigador principal:
- Craig J McClain, M.D.
-
Investigador principal:
- Vatsalya Vatsalya, M.D.
-
Investigador principal:
- Ventakrishna R Jala, Ph.D.
-
Contacto:
- Vatsalya Vatsalya, M.D.
- Número de teléfono: 502-852-8928
- Correo electrónico: v0vats01@louisville.edu
-
Contacto:
- Steve Mahanes, M.S.
- Número de teléfono: 502-852-1388
- Correo electrónico: steve.mahanes@louisville.edu
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
Healthy Group:
Inclusion: Healthy individuals, Exclusion: AUD, ALD, AC, and inflammatory conditions,
Alcohol Use Disorder Group:
Inclusion: AUD diagnosis Exclusion: alcohol-associated systemic conditions
Alcohol-associated liver disease Group:
Inclusion: early-stage ALD comorbid with AUD Exclusion: Only AUD or AUD with AC
Alcohol-associated cirrhosis Inclusion: AC with AUD Exclusion: AUD, and early stage ALD, as well as determined by the study cohort criteria
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
healthy volunteers
Adults ≥18, Drink no alcohol or drink < 50 grams of alcohol per day on average if female and < 80 grams per day on average if male; 3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
|
Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Otros nombres:
|
|
Alcohol Use Disorder (AUD) subjects
Adults ≥18; Must consume >20 standardized alcoholic beverages a week for the last 3 months for men, >14 standard alcoholic beverages a week for women; 3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
|
Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Otros nombres:
|
|
Alcoho-associated Cirrhosis (AC) patients
Adults ≥18; A history of alcohol consumption averaging at least 80 grams per day in men or 50 grams per day for women for at least 10 years; 3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
|
Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Otros nombres:
|
|
Early-Stage Alcohol-Associated Liver Disease
Adults ≥18; AUD qualifying criteria, plus ALT>40.
3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
|
Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
To characterize the metabolite and cytokine profiles to inform future trials designed for enhancing cut barrier function
Periodo de tiempo: 2036 yr.
|
To evaluate the impact of pomegranate dietary supplements (PDS) on gut microbiome composition and epithelial barrier function in healthy, alcohol use disorder (AUD), early-stage ALD (eALD), and alcohol-associated liver cirrhosis (AC) subjects by characterizing the metabolite and cytokine profiles to inform future trials designed for enhancing cut barrier function in alcohol-associated liver disease (ALD).
|
2036 yr.
|
|
If inter-individual variation in gut microbiome is responsible for the production of beneficial metabolites
Periodo de tiempo: 2036 yr.
|
To determine if inter-individual variation in gut microbiome is responsible for the production of beneficial metabolites in healthy, AUD, eALD, and AC patients by correlating urolithin levels to inflammatory mediators in both healthy and diseased conditions.
|
2036 yr.
|
|
To determine if more correlative studies between produced metabolites, inflammatory mediators, and disease conditions could provide informed decisions during disease progression.
Periodo de tiempo: 2036 yr.
|
Develop identifiers for the pathology and treatment development of the study cohorts.
|
2036 yr.
|
|
To evaluate the omics of the subject and the microbiomes in their saliva, urine, and stool.
Periodo de tiempo: 2036 yr.
|
To evaluate the omics of the subject and the microbiomes in their saliva, urine, and stool.
This will help determine what response changes are genetic changes (both bacterial and human) in saliva; and omics, and genetic changes in stool and urine (both human and bacterial) could illustrate their role in profiling these potential modifiable risk factors for AUD/ALD.
The data could be correlated with the blood sample-derived cytokine, gut dysfunction, and candidate biomarkers of liver (K18s) and AUD severity (neurotransmitters, such as dopamine, GABA, serotonin, etc.)
|
2036 yr.
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Craig J McClain, MD, University of Louisville
- Director de estudio: Vatsalya Vatsalya, MD, University of Louisville
- Investigador principal: Venkatakrishna R Jala, PhD, University of Louisville
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
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
- Desordenes mentales
- Procesos Patológicos
- Enfermedades del Sistema Digestivo
- Enfermedades del HIGADO
- Trastornos relacionados con sustancias
- Trastornos inducidos químicamente
- Trastornos relacionados con el alcohol
- Fibrosis
- Cirrosis hepática
- Enfermedades Hepáticas Alcohólicas
- Trastornos inducidos por el alcohol
- Condiciones Patológicas, Signos y Síntomas
- Alcoholismo
- Cirrosis Hepática Alcohólica
Otros números de identificación del estudio
- 21.0999
- 2P50AA024337 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de 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.
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. .