Clinical trial NCT06059131: Effect of a Specific Aquaporin-1 Inhibitor on Vascular Oxidative Stress in Healthy Volunteers
Official title: Randomized Controlled and Double-blinded Study of the Effect of a Specific Aquaporin-1 Inhibitor, Bacopaside II (KeenMind®), on Vascular Oxidative Stress in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Oxidative Stress
Cardiovascular Diseases
Bacopaside II
Bacopa Monnieri
Endothelial Dysfunction
Aquaporin 1
AQP1
Keywords: vascular oxidative stress
aquaporin 1
AQP1
peroxiporin
H2O2
hydrogen peroxide
cardiovascular diseases
Bacopa monnieri
Bacopaside II
endothelial dysfunction
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Université Catholique de Louvain
First posted: 2023-09-28
Enrollment: 40
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 arms : placebo vs verum
Primary purpose: PREVENTION

Brief summary: Bacoxy_II study aims to evaluate the efficacy of a standardized Bacopa monnieri extract, KeenMind®, on vascular oxidative stress.

Detailed description: The food supplement Bacopa monnieri is a plant used in Ayuverda medicine, especially in the treatment of chronic neurological disease with cognitive impairment and memory disorders and for stress management.

Bacopa monnieri contains several Bacosides including Bacopaside II, a specific inhibitor of aquaporin 1 (AQP1), the main water chanel found in mammalian cardiovacular tissues.

AQP1, more than a water chanel, is a peroxiporin able to facilitate the passage of H2O2.

AQP1 is present in myocyte, endothelial and red blood cells. Concerning the endothelial function, analyses in the FATH laboratory (IREC - UCLouvain), confirm the attenuation of H2O2 transport by AQP1 through Bacopaside II in red blood cells but also in endothelial cells.

As H2O2 is involved in oxidative stress mechanisms and endothelial dysfunction, the investigators hypothezised that the oral intake of Bacopa monnieri containing the Bacopaside II could induce an inhibition of AQP1 and attenuate the passage of H2O2 leading to an attenuation of vascular oxidative stress and endothelial function.

In order to answer to this question, the investigators set up the Bacoxy_II clinical study, that is a double-blind, prospective, interventional and controlled study. The study will last 4 months, including 3 months of treatment and 1 month of post-treatment follow-up. This study will include 2 groups of 20 volunteers: one group will receive a dose of 320 mg/d of Bacopa monnieri and the other group will receive the placebo treatment.

Eligibility criteria: Inclusion Criteria:

- healthy volunteers

Exclusion Criteria:

* any chronic disease
* use of chronic drugs or food supplements
* smoking

Primary outcomes:
measure: Ex vivo DCFDA test on red blood cells (RBCs)
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Nitrosylated hemoglobin (HbNO)
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Lipid peroxydes
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: EndoPAT
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
Secondary outcomes:
measure: C-reactive protein (CRP)
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Blood count
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Ion count
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Lipid count
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Liver function
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Kidney function
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: HOMA index
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Body mass index, fat mass, lean mass,
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
measure: Waist and hip circumference ratio
timeFrame: Baseline (V0), 3 months (V1), 4 months (V2)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
state: Belgique
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Virginie Montiel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pravina K, Ravindra KR, Goudar KS, Vinod DR, Joshua AJ, Wasim P, Venkateshwarlu K, Saxena VS, Amit A. Safety evaluation of BacoMind in healthy volunteers: a phase I study. Phytomedicine. 2007 May;14(5):301-8. doi: 10.1016/j.phymed.2007.03.010. Epub 2007 Apr 17.
citation: Stough C, Downey LA, Lloyd J, Silber B, Redman S, Hutchison C, Wesnes K, Nathan PJ. Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial. Phytother Res. 2008 Dec;22(12):1629-34. doi: 10.1002/ptr.2537.
citation: Dave UP, Dingankar SR, Saxena VS, Joseph JA, Bethapudi B, Agarwal A, Kudiganti V. An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in children. Adv Mind Body Med. 2014 Spring;28(2):10-5.
citation: Montiel V, Leon Gomez E, Bouzin C, Esfahani H, Romero Perez M, Lobysheva I, Devuyst O, Dessy C, Balligand JL. Genetic deletion of aquaporin-1 results in microcardia and low blood pressure in mouse with intact nitric oxide-dependent relaxation, but enhanced prostanoids-dependent relaxation. Pflugers Arch. 2014 Feb;466(2):237-51. doi: 10.1007/s00424-013-1325-x. Epub 2013 Jul 20.
citation: Montiel V, Bella R, Michel LYM, Esfahani H, De Mulder D, Robinson EL, Deglasse JP, Tiburcy M, Chow PH, Jonas JC, Gilon P, Steinhorn B, Michel T, Beauloye C, Bertrand L, Farah C, Dei Zotti F, Debaix H, Bouzin C, Brusa D, Horman S, Vanoverschelde JL, Bergmann O, Gilis D, Rooman M, Ghigo A, Geninatti-Crich S, Yool A, Zimmermann WH, Roderick HL, Devuyst O, Balligand JL. Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide. Sci Transl Med. 2020 Oct 7;12(564):eaay2176. doi: 10.1126/scitranslmed.aay2176.