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Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges
Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797052/ https://www.ncbi.nlm.nih.gov/pubmed/35096945 http://dx.doi.org/10.3389/fnut.2021.799137 |
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author | Wright, Kirsten M. McFerrin, Janis Alcázar Magaña, Armando Roberts, Joanne Caruso, Maya Kretzschmar, Doris Stevens, Jan F. Maier, Claudia S. Quinn, Joseph F. Soumyanath, Amala |
author_facet | Wright, Kirsten M. McFerrin, Janis Alcázar Magaña, Armando Roberts, Joanne Caruso, Maya Kretzschmar, Doris Stevens, Jan F. Maier, Claudia S. Quinn, Joseph F. Soumyanath, Amala |
author_sort | Wright, Kirsten M. |
collection | PubMed |
description | Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active components and biological targets. Translation away from preclinical models, and developing an optimized, reproducible botanical product for use in clinical trials, presents particular challenges for phytotherapeutic agents compared to single chemical entities. Common deficiencies noted in clinical trials of botanical products include limited characterization of the product tested, inadequate placebo control, and lack of rationale for the type of product tested, dose used, outcome measures or even the study population. Our group has focused on the botanical Centella asiatica due to its reputation for enhancing cognition in Eastern traditional medicine systems. Our preclinical studies on a Centella asiatica water extract (CAW) and its bioactive components strongly support its potential as a phytotherapeutic agent for cognitive decline in aging and Alzheimer's disease through influences on antioxidant response, mitochondrial activity, and synaptic density. Here we describe our robust, scientific approach toward developing a rational phytotherapeutic product based on Centella asiatica for human investigation, addressing multiple factors to optimize its valid clinical evaluation. Specific aspects covered include approaches to identifying an optimal dose range for clinical assessment, design and composition of a dosage form and matching placebo, sourcing appropriate botanical raw material for product manufacture (including the evaluation of active compounds and contaminants), and up-scaling of laboratory extraction methods to available current Good Manufacturing Practice (cGMP) certified industrial facilities. We also address the process of obtaining regulatory approvals to proceed with clinical trials. Our study highlights the complexity of translational research on botanicals and the importance of identifying active compounds and developing sound analytical and bioanalytical methods for their determination in botanical materials and biological samples. Recent Phase I pharmacokinetic studies of our Centella asiatica product in humans (NCT03929250, NCT03937908) have highlighted additional challenges associated with designing botanical bioavailability studies, including specific dietary considerations that need to be considered. |
format | Online Article Text |
id | pubmed-8797052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87970522022-01-29 Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges Wright, Kirsten M. McFerrin, Janis Alcázar Magaña, Armando Roberts, Joanne Caruso, Maya Kretzschmar, Doris Stevens, Jan F. Maier, Claudia S. Quinn, Joseph F. Soumyanath, Amala Front Nutr Nutrition Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active components and biological targets. Translation away from preclinical models, and developing an optimized, reproducible botanical product for use in clinical trials, presents particular challenges for phytotherapeutic agents compared to single chemical entities. Common deficiencies noted in clinical trials of botanical products include limited characterization of the product tested, inadequate placebo control, and lack of rationale for the type of product tested, dose used, outcome measures or even the study population. Our group has focused on the botanical Centella asiatica due to its reputation for enhancing cognition in Eastern traditional medicine systems. Our preclinical studies on a Centella asiatica water extract (CAW) and its bioactive components strongly support its potential as a phytotherapeutic agent for cognitive decline in aging and Alzheimer's disease through influences on antioxidant response, mitochondrial activity, and synaptic density. Here we describe our robust, scientific approach toward developing a rational phytotherapeutic product based on Centella asiatica for human investigation, addressing multiple factors to optimize its valid clinical evaluation. Specific aspects covered include approaches to identifying an optimal dose range for clinical assessment, design and composition of a dosage form and matching placebo, sourcing appropriate botanical raw material for product manufacture (including the evaluation of active compounds and contaminants), and up-scaling of laboratory extraction methods to available current Good Manufacturing Practice (cGMP) certified industrial facilities. We also address the process of obtaining regulatory approvals to proceed with clinical trials. Our study highlights the complexity of translational research on botanicals and the importance of identifying active compounds and developing sound analytical and bioanalytical methods for their determination in botanical materials and biological samples. Recent Phase I pharmacokinetic studies of our Centella asiatica product in humans (NCT03929250, NCT03937908) have highlighted additional challenges associated with designing botanical bioavailability studies, including specific dietary considerations that need to be considered. Frontiers Media S.A. 2022-01-14 /pmc/articles/PMC8797052/ /pubmed/35096945 http://dx.doi.org/10.3389/fnut.2021.799137 Text en Copyright © 2022 Wright, McFerrin, Alcázar Magaña, Roberts, Caruso, Kretzschmar, Stevens, Maier, Quinn and Soumyanath. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Nutrition Wright, Kirsten M. McFerrin, Janis Alcázar Magaña, Armando Roberts, Joanne Caruso, Maya Kretzschmar, Doris Stevens, Jan F. Maier, Claudia S. Quinn, Joseph F. Soumyanath, Amala Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges |
title | Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges |
title_full | Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges |
title_fullStr | Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges |
title_full_unstemmed | Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges |
title_short | Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges |
title_sort | developing a rational, optimized product of centella asiatica for examination in clinical trials: real world challenges |
topic | Nutrition |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797052/ https://www.ncbi.nlm.nih.gov/pubmed/35096945 http://dx.doi.org/10.3389/fnut.2021.799137 |
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