Vascular Aging and Lp299v Study in Healthy Adults

NCT05296395 | Active Not Recruiting

• 1 other identifier: PRO43157
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Emerging data suggest the gut microbiota regulates multiple mechanisms related to vascular aging, but no intervention targeting the gut microbiota has been tested in older adults without cardiovascular risk factors or cardiovascular disease. Early human data suggest an increase in potentially pathological gut metabolites such as trimethylamine-N-oxide (TMAO) are associated with older age, increased vascular stiffness, increased oxidative stress, and reduced nitric oxide (NO) bioavailability as evidenced by impaired endothelium-dependent vasodilation. Based on this data, the investigators hypothesize that supplementation with Lp299v will reverse human vascular aging in healthy older adults free of known traditional cardiovascular risk factors.

Conditions

Vascular Aging

Keywords

Endothelial Function; Microbiome

Outcome Measures

Primary Outcomes (1)

• Brachial Artery Flow Mediated Dilation (FMD%

  This is a measurement of endothelial function in the brachial artery

  6 weeks

Secondary Outcomes (6)

• Nitroglycerin-Mediated Vasodilation of the brachial artery (NMD)

  6 weeks

• Hyperemic Flow Velocity

  6 weeks

• Carotid-Femoral Pulse Wave Velocity (cfPWV)

  6 weeks

• Stool microbiota alpha diversity

  6 weeks

• Stool microbiota beta diversity

  6 weeks

Study Arms (2)

Lp299v

EXPERIMENTAL

Subjects will consume 20 billion colony forming units of Lp299v (1 serving of GoodBelly fermented oat drink) once daily for 6 weeks

Other: Lactobacillus Plantarum 299v in fermented oat drink

Heat-killed placebo control

PLACEBO COMPARATOR

Subjects will consume 1 serving of GoodBelly fermented oat drink that has been treated to heat kill all Lp299v once daily for 6 weeks

Other: Heat-Killed Placebo control fermented drink

Interventions

Lactobacillus Plantarum 299v in fermented oat drink OTHER

The intervention is a probiotic lactobacillus that is contained in food products in the US

Also known as: GoodBelly StraighShot

Lp299v

Heat-Killed Placebo control fermented drink OTHER

The intervention is the GoodBelly StraightShort that has been treated to heat kill all Lp299v

Heat-killed placebo control

Eligibility Criteria

• Age: 50 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 50-99 years
• For women: 12 months or more since last menstruation

You may not qualify if:

• Systolic Blood Pressure ≥ 130 mmHg or Diastolic BP ≥ 80mmHg
• Currently taking pharmacological therapies for hypertension, dyslipidemia, or glucose control
• Diabetes (type 1 or 2) or glycosylated hemoglobin ≥ 5/7%
• LDL Cholesterol \> 160 mg/dL or Total Cholesterol \> 200 mg/dL
• Cigarette use within 3 years of enrollment
• Average of \> 7500 steps per day as measured during screening period
• Received probiotics, prebiotics, and/or antibiotics within six weeks of enrollment
• History of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within 3 years of enrollment
• History of inflammatory rheumatic diseases known to increase atherosclerotic cardiovascular risk (e.g. rheumatoid arthritis, systemic lupus erythematosus)
• Known history of cognitive impairment or inability to follow study procedures
• GI tract illnesses such as short gut syndrome, inflammatory bowel disease, or an ileostomy
• Daily alcohol use

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (22)

• Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O'Connor M, Harnedy N, O'Connor K, Henry C, O'Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O'Toole PW. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4586-91. doi: 10.1073/pnas.1000097107. Epub 2010 Jun 22.

  PMID: 20571116 BACKGROUND

• Hebuterne X. Gut changes attributed to ageing: effects on intestinal microflora. Curr Opin Clin Nutr Metab Care. 2003 Jan;6(1):49-54. doi: 10.1097/00075197-200301000-00008.

  PMID: 12496680 BACKGROUND

• Menni C, Lin C, Cecelja M, Mangino M, Matey-Hernandez ML, Keehn L, Mohney RP, Steves CJ, Spector TD, Kuo CF, Chowienczyk P, Valdes AM. Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J. 2018 Jul 1;39(25):2390-2397. doi: 10.1093/eurheartj/ehy226.

  PMID: 29750272 BACKGROUND

• Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Ter Horst R, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ. Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell. 2016 Nov 3;167(4):1125-1136.e8. doi: 10.1016/j.cell.2016.10.020.

  PMID: 27814509 BACKGROUND

• Brunt VE, Gioscia-Ryan RA, Richey JJ, Zigler MC, Cuevas LM, Gonzalez A, Vazquez-Baeza Y, Battson ML, Smithson AT, Gilley AD, Ackermann G, Neilson AP, Weir T, Davy KP, Knight R, Seals DR. Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice. J Physiol. 2019 May;597(9):2361-2378. doi: 10.1113/JP277336. Epub 2019 Feb 27.

  PMID: 30714619 BACKGROUND

• Brunt VE, Gioscia-Ryan RA, Casso AG, VanDongen NS, Ziemba BP, Sapinsley ZJ, Richey JJ, Zigler MC, Neilson AP, Davy KP, Seals DR. Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans. Hypertension. 2020 Jul;76(1):101-112. doi: 10.1161/HYPERTENSIONAHA.120.14759. Epub 2020 Jun 10.

  PMID: 32520619 BACKGROUND

• Ke Y, Li D, Zhao M, Liu C, Liu J, Zeng A, Shi X, Cheng S, Pan B, Zheng L, Hong H. Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radic Biol Med. 2018 Feb 20;116:88-100. doi: 10.1016/j.freeradbiomed.2018.01.007. Epub 2018 Jan 8.

  PMID: 29325896 BACKGROUND

• Li T, Chen Y, Gua C, Li X. Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress. Front Physiol. 2017 May 30;8:350. doi: 10.3389/fphys.2017.00350. eCollection 2017.

  PMID: 28611682 BACKGROUND

• Brandsma E, Kloosterhuis NJ, Koster M, Dekker DC, Gijbels MJJ, van der Velden S, Rios-Morales M, van Faassen MJR, Loreti MG, de Bruin A, Fu J, Kuipers F, Bakker BM, Westerterp M, de Winther MPJ, Hofker MH, van de Sluis B, Koonen DPY. A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. Circ Res. 2019 Jan 4;124(1):94-100. doi: 10.1161/CIRCRESAHA.118.313234.

  PMID: 30582442 BACKGROUND

• Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Horst RT, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ. Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell. 2016 Dec 15;167(7):1897. doi: 10.1016/j.cell.2016.11.046. No abstract available.

  PMID: 27984736 BACKGROUND

• Geva-Zatorsky N, Sefik E, Kua L, Pasman L, Tan TG, Ortiz-Lopez A, Yanortsang TB, Yang L, Jupp R, Mathis D, Benoist C, Kasper DL. Mining the Human Gut Microbiota for Immunomodulatory Organisms. Cell. 2017 Feb 23;168(5):928-943.e11. doi: 10.1016/j.cell.2017.01.022. Epub 2017 Feb 16.

  PMID: 28215708 BACKGROUND

• Sharma R, Padwad Y. Probiotic bacteria as modulators of cellular senescence: emerging concepts and opportunities. Gut Microbes. 2020 May 3;11(3):335-349. doi: 10.1080/19490976.2019.1697148. Epub 2019 Dec 10.

  PMID: 31818183 BACKGROUND

• Wu CS, Muthyala SDV, Klemashevich C, Ufondu AU, Menon R, Chen Z, Devaraj S, Jayaraman A, Sun Y. Age-dependent remodeling of gut microbiome and host serum metabolome in mice. Aging (Albany NY). 2021 Feb 17;13(5):6330-6345. doi: 10.18632/aging.202525. Epub 2021 Feb 17.

  PMID: 33612480 BACKGROUND

• Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, Pluznick JL. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genomics. 2016 Nov 1;48(11):826-834. doi: 10.1152/physiolgenomics.00089.2016. Epub 2016 Sep 23.

  PMID: 27664183 BACKGROUND

• Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012 Feb;61(2):364-71. doi: 10.2337/db11-1019. Epub 2011 Dec 21.

  PMID: 22190648 BACKGROUND

• Ding L, Zhang J. Glucagon-like peptide-1 activates endothelial nitric oxide synthase in human umbilical vein endothelial cells. Acta Pharmacol Sin. 2012 Jan;33(1):75-81. doi: 10.1038/aps.2011.149. Epub 2011 Nov 28.

  PMID: 22120969 BACKGROUND

• Chai W, Dong Z, Wang N, Wang W, Tao L, Cao W, Liu Z. Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes. 2012 Apr;61(4):888-96. doi: 10.2337/db11-1073. Epub 2012 Feb 22.

  PMID: 22357961 BACKGROUND

• Tsiotra PC, Boutati E, Dimitriadis G, Raptis SA. High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells. Biomed Res Int. 2013;2013:487081. doi: 10.1155/2013/487081. Epub 2012 Dec 24.

  PMID: 23484124 BACKGROUND

• Yang WH, Liu SC, Tsai CH, Fong YC, Wang SJ, Chang YS, Tang CH. Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts. PLoS One. 2013 Sep 27;8(9):e75551. doi: 10.1371/journal.pone.0075551. eCollection 2013.

  PMID: 24086566 BACKGROUND

• Tang CH, Lu DY, Yang RS, Tsai HY, Kao MC, Fu WM, Chen YF. Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol. 2007 Jul 15;179(2):1292-302. doi: 10.4049/jimmunol.179.2.1292.

  PMID: 17617622 BACKGROUND

• Tazawa R, Uchida K, Fujimaki H, Miyagi M, Inoue G, Sekiguchi H, Murata K, Takata K, Kawakubo A, Takaso M. Elevated leptin levels induce inflammation through IL-6 in skeletal muscle of aged female rats. BMC Musculoskelet Disord. 2019 May 10;20(1):199. doi: 10.1186/s12891-019-2581-5.

  PMID: 31077169 BACKGROUND

• Naruszewicz M, Johansson ML, Zapolska-Downar D, Bukowska H. Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers. Am J Clin Nutr. 2002 Dec;76(6):1249-55. doi: 10.1093/ajcn/76.6.1249.

  PMID: 12450890 BACKGROUND

Study Officials

• Michael E Widlansky, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: March 25, 2022
• Study Start: February 1, 2023
• Primary Completion (Estimated): September 22, 2026
• Study Completion (Estimated): September 22, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Within 1 year of completion of publication of study.
• Access Criteria: Data will be available to qualified investigators.

Locations

US (1)