Project description:The VISP trial (PI Jim Toole, M.D., Wake Forest University School of Medicine) was a multi-center, double-blind, randomized, controlled clinical trial that enrolled patients aged 35 or older with Hcy levels above the 25th percentile at screening and a non-disabling cerebral infarction (NDCI) within 120 days of randomization [Toole, 2002]. The trial was designed to determine if daily intake of a multivitamin tablet with high dose folic acid, vitamin B6 and vitamin B12 reduced recurrent cerebral infarction (primary endpoint), and nonfatal myocardial infarction (MI) or mortality (secondary endpoints). Subjects were randomly assigned to receive daily doses of the high-dose formulation (n=1,827), containing 25mg pyridoxine (B6), 0.4mg cobalamin (B12), and 2.5mg folic acid; or the low-dose formulation (n=1,853), containing 200mcg pyridoxine, 6mcg cobalamin and 20mcg folic acid. Enrollment in VISP began in August 1997, and was completed in December 2001, with 3,680 participants enrolled. Within the trial, 2,164 participants from 46 clinic sites provided DNA and agreed for it to be shared for use in a genetic subset study of VISP. This study is part of the Genomics and Randomized Trials Network (GARNET, <a href="http://www.garnetstudy.org" target="_blank">http://www.garnetstudy.org</a>) funded by the National Human Genome Research Institute (NHGRI). The overarching goal is to identify novel genetic factors that contribute to stroke through large-scale genome-wide association studies of treatment response in randomized clinical trials. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were performed at the GARNET Coordinating Center at the University of Washington. The data of the VISP trial have been released to dbGaP users in several segments: Version 1 (phs000343.v1.p1), consisted of n=4 phenotype datasets, and all raw, cleaned and imputed genotype data. Version 2 (phs000343.v2.p1) included n=14 additional phenotype datasets (plus pedigree, consent, and sample-mapping data), and increased the available data to a total of n=970 phenotype variables. Version 3 (phs000343.v3.p1), the current release, includes all n=36 phenotype datasets (plus pedigree, consent, and sample-mapping data), and increases the available data to a total of n=1918 phenotype variables. Toole, J. F. (2002). Vitamin intervention for stroke prevention. J Neurol Sci, 203-204, 121-4. PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/12417369" target="_blank">12417369</a>.

Project description:The VISP trial (PI Jim Toole, M.D., Wake Forest University School of Medicine) was a multi-center, double-blind, randomized, controlled clinical trial that enrolled patients aged 35 or older with Hcy levels above the 25th percentile at screening and a non-disabling cerebral infarction (NDCI) within 120 days of randomization [Toole, 2002]. The trial was designed to determine if daily intake of a multivitamin tablet with high dose folic acid, vitamin B6 and vitamin B12 reduced recurrent cerebral infarction (primary endpoint), and nonfatal myocardial infarction (MI) or mortality (secondary endpoints). Subjects were randomly assigned to receive daily doses of the high-dose formulation (n=1,827), containing 25mg pyridoxine (B6), 0.4mg cobalamin (B12), and 2.5mg folic acid; or the low-dose formulation (n=1,853), containing 200µg pyridoxine, 6 µg cobalamin and 20µg folic acid. Enrollment in VISP began in August 1997, and was completed in December 2001, with 3,680 participants enrolled. Within the trial, 2,164 participants from 46 clinic sites provided DNA and agreed for it to be shared for use in a genetic subset study of VISP. This study is part of the Genomics and Randomized Trials Network (GARNET, <a href="http://www.garnetstudy.org" target="_blank">http://www.garnetstudy.org</a>) funded by the National Human Genome Research Institute (NHGRI). The overarching goal is to identify novel genetic factors that contribute to stroke through large-scale genome-wide association studies of treatment response in randomized clinical trials. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were performed at the GARNET Coordinating Center at the University of Washington. The data of the VISP trial will be released to dbGaP users in several segments; the current segment, version 1 (phs000343.v1.p1), consists of n=4 phenotype datasets, and all raw, cleaned and imputed genotype data. Toole, J. F. (2002). Vitamin intervention for stroke prevention. J Neurol Sci, 203-204, 121-4. PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/12417369" target="_blank">12417369</a>.

Project description:Urolithin A is a gut microbiome derived postbiotic that has been shown to stimulate mitophagy, and improve muscle and mitochondrial health when administered orally to humans. In three separate randomized trials, we have now investigated the effect of topical administration of Urolithin A on skin aging features and on UVB-mediated photodamaged skin. Post-menopausal women with evidence of skin aging such as > Grade 3 wrinkle formation were included in a split-face/arm study design in the first trial (aging study 1; n=48), followed by a second larger trial (aging study 2; n=108) in middle-aged men and women focusing on wrinkle reduction. Healthy participants were included in the placebo-controlled, randomized UVB-induced trial (photo-damage trial; n=22). Participants were randomized to receive topical supplementation with either 0.5% Urolithin A cream or placebo for 8-weeks in a low-dose arm or 1% Urolithin A cream or placebo in the high-dose arm in theaging study 1. In theaging study 2participants were randomized to receive 1% UA in a day-cream, a night cream and a serum, that were compared to the untreated site. For thephoto-damage trial,topical patches containing either 0.5% or 1% UA or placebo cream were applied for 24-hours following UVB irradiation. The primary outcome in theaging study 1was an impact on biological pathways linked to skin aging in skin biopsies, and an impact on skin barrier function after 8-weeks. Key secondary endpoints were a change in facial wrinkle appearance (crow’s feet area). Theaging study 2focused on wrinkle reduction as a primary outcome. In the UVB-mediatedphoto-damage study, the primary read-out was the change in erythema after application. Molecular analyses were conducted on skin biopsies and usingex-vivosystems to investigate the mechanism of action mediating skin protective effects of Urolithin A. In theaging study 1, Urolithin A at 1% significantly up-regulated collagen synthesis pathways in human skin biopsies and led to a decrease in wrinkle depth on facial wrinkles. The lower dose had no significant impact. There was no change on skin barrier function with both doses suggesting maintenance of a healthy skin barrier function. Inaging study 2, topical application of Urolithin A at the 1% dose in different formulations (day-cream, night cream and serum) led to significant wrinkle reduction compared to the untreated side, confirming the previous findings. Skin hydration was improved significantly as well. In the third trial, investigating impact on photodamaged skin, Urolithin A application led to a significant decrease in UV-induced erythema (∼14%) compared to the untreated area, while placebo and lower dose UA cream’s showed no benefits. Urolithin A topical administration was safe and well-tolerated in all studies. UA also inhibited collagen degrading and pro-inflammatory pathways and up-regulated gene expression of biomarkers linked to induction of mitophagy and autophagy in human skin cells. Taken together, these clinical studies support the topical use of Urolithin A to manage and prolong skin health longevity by acting at the cellular level, supporting collagen structure, reducing wrinkle appearance and protecting against photoaging.

Dataset Information

Genomics and Randomized Trials Network (GARNET)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets