Clinical trial NCT06355167: Effect of Oral Intake of Bacopa Monneiri on Vascular Oxidative Stress
Official title: Interventional, Open-label Study of the Effect of an Aquaporin-1 Inhibitor, the Bacopaside II Contained in Bacopa-400® , on Oxidative Stress in Healthy Volunteers: BacOxy_I Study
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
hydrogen peroxide
cardiovascular diseases
Bacopa monnieri
Bacopaside II
endothelial dysfunction
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group A (n=10): 400mg/d of Bacopa monnieri Broup B (n=10): 800 mg/d of Bacopa monnieri
Primary purpose: PREVENTION

Brief summary: Bacoxy_I study aims to evaluate the efficacy of a standardized Bacopa monnieri extract, Bacopa-400®, on vascular oxidative stress.

Detailed description: The Bacopa-400® is a standardized extract of a plant called Bacopa Monnieri, which mainly grows in India and neighboring countries. The virtues of this plant, also called Brahmi, have been used in Ayurvedic medicine for millennia in the treatment of chronic neurological diseases accompanied by cognitive impairment and memory disorders, as well as for stress management. Several companies have subsequently improved the preparation of standardized extracts of Bacopa Monnieri. Bacopa-400® from the Belgian firm Deba Pharma™ was selected because it adheres to good manufacturing practices (GMP). Currently, there are over 289 studies listed regarding the positive role of Bacopa monnieri in cognitive functions in both young and elderly subjects. Furthermore, no major side effects have been reported following the use of this plant extract in acute or chronic administration in hundreds of people of all ages.

Bacopa monnieri plant contains several bacosides, including the Bacopaside II a specific inhibitor of the water channel Aquaporin 1 (AQP1). AQP1 is part of the aquaporin family responsible for bidirectional transmembrane water transport. It is the most abundant aquaporin in mammalian cardiovascular tissue, present in myocardial cells, endothelial cells, and red blood cells. AQP1, more than a water channel, is also a peroxiporin able to facilitate the passage of hydrogen peroxide (H2O2), involved in oxidative stress.

In previous work, the Pharmacology and Therapeutics (FATH) department from UCLouvain (Brussels) discovered the protective effect of Bacopaside II on cardiovascular oxidative stress. Through a series of experiments, it was demonstrated that Bacopaside II dose dependently attenuates the passage of H2O2 into cardiac myocytes, thus preventing hypertrophy induced by neurohormones. Additionally, in murine models, oral administration of Bacopa monnieri extract attenuated cardiac hypertrophy triggered by hypertrophic stimuli. This cardiac protection occurs through inhibition of AQP1.

Based on this premises, a clinical investigation was undertaken to explore the potential of Bacopa-400® in attenuating vascular oxidative stress among healthy volunteers. This interventional, open-label and monocentric comprised two groups. Group A received a daily dose of 400 mg and Group B a daily dose of 800 mg over a 6-week period, followed by a 4-week observation period after the cessation of treatment.

The primary objective of this study was to assess the impact of Bacopa-400® on oxidative stress in healthy individuals and determine the optimal dosage for maximal efficacy. Furthermore, the study analyzed the incidence, severity, and frequency of adverse events, including suspected unexpected serious adverse events (SUSAR).

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers
* Effective contraception

Exclusion Criteria:

* Any chronic disease
* Any chronic use of drug
* Pregnancy and breast feeding
* Gastro-intestinal diseases (e.g. ulcer, gastro-oesophageal reflux, lactose intolerance)

Primary outcomes:
measure: Ex vivo DCFDA test on red blood cells (RBCs)
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Plasma lipid peroxydes
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Methemoglobin in red blood cells
timeFrame: Baseline (V0), 6 weeks (V4), 10 weeks (V6)
measure: Nitrosylated hemoglobin (HbNO) in red blood cells
timeFrame: Baseline (V0), 6 weeks (V4), 10 weeks (V6)
Secondary outcomes:
measure: haemoglobin
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: haematocrit
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Red blood cells count
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Sodium
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Potassium
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Bicarbonate
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Total cholesterol
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: High-Density Lipoprotein (HDL) cholesterol
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Low-Density Lipoprotein (LDL) cholesterol
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Triglycerides
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: aspartate aminotransferase (ASAT), (U/L)
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: alanine aminotransferase (ALAT) (U/L)
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: gamma-glutamyl-transferase (GGT) level
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Creatinine
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
measure: Glomerular filtration rate
timeFrame: Baseline (V0), 2 weeks (V2), 6 weeks (V4), 10 weeks (V6)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Clinique universitaires saint luc
Study officials:
References:
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.
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.
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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.