DisbiosisNCT07530575
Limosilactobacillus Fermentum CRL 1446 - CONICET CASASCO
A study testing Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU in people with Disbiosis and Obesity, run by PINER Pastor Manfredi Winery at 2 sites in Argentina.
Trial summary
This research study aims to determine if a probiotic called Limosilactobacillus fermentum CRL 1446 can improve the health of people at risk for cardiovascular disease. The study will be conducted with volunteers who will randomly consume either the probiotic or a placebo (a capsule without the probiotic), without… Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Disbiosis, Obesity, Overweight (BMI > 25)
- What is being tested?
- Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesArgentina
- Study dates
- 2 Feb 2026to 21 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Volunteers with the following conditions may be eligible:
- Blood glucose greater than 100 mg/dl or pharmacological treatment for high blood glucose levels;
- HDL cholesterol < 40 mg/dl in men or < 50 mg/dl in women, or pharmacological treatment for low HDL cholesterol levels;
- Blood triglycerides > 150 mg/dl or pharmacological treatment for high triglyceride levels;
- Waist circumference > 102 cm for men or > 88 cm for women;
- Arterial pressure > 130/85 mmHg;
- Sedentarism;
- Smoking habit.
Who cannot join
- Patients with a history of digestive surgeries, inflammatory bowel disease, patients with gastroenteritis in the last 6 months, cancer patients, patients with rheumatic pathologies, patients with liver disorders, immunological disorders or deficiencies, steatorrhea, antibiotic use in the last 3 months, or anemia of any cause or pregnancy/expectation of becoming pregnant during the study.
- -
Trial locations and contacts
2 sites in 1 country.
Argentina2 sites
Raul Francisco Pastor
Buenos Aires, Buenos Aires City, 1408
TIEMPO MEDICO Health Research Center
Buenos Aires, 1440
About this study
Official title: Biological Effects of the Consumption of Limosilactobacillus Fermentum CRL 1446 - CONICET in Volunteers With Cardiovascular Risk Factors
This research study aims to determine if a probiotic called Limosilactobacillus fermentum CRL 1446 can improve the health of people at risk for cardiovascular disease.
The study will be conducted with volunteers who will randomly consume either the probiotic or a placebo (a capsule without the probiotic), without knowing which one they are taking. The researchers will analyze how the probiotic affects blood sugar control, body composition, inflammation, and oxidative stress. The goal is to determine if this beneficial bacterium, by influencing the gut microbiota, could be a new strategy to prevent or mitigate chronic heart diseases.
Read the detailed description
The clinical study protocol, titled "Biological Effects of Consuming Limosilactobacillus fermentum CRL 1446 CONICET in Volunteers with Cardiovascular Risk Factors" was issued in October 2025 in Version 3.
Rationale and Theoretical Background
The protocol is underpinned by the acknowledgment of the key influence of the gut microbiota on human health, especially concerning cardiovascular risk factors. Data from Argentina's Fourth National Risk Factor Survey indicates a rise in overweight and obesity from 49% in 2005 to 61.6% in 2018. Overweight and obesity, along with dyslipidemia, hypertension, insulin resistance, and chronic inflammation, are closely correlated with imbalances in the gut microbiota, known as dysbiosis, which elevates the risk of cardiovascular diseases. Dysbiosis is characterized by a reduction in bacterial diversity, an increase in pro-inflammatory bacteria, and a decrease in beneficial bacteria that produce short-chain fatty acids.
Nutritional intervention utilizing probiotics presents a promising alternative for modulating the gut microbiota's composition and function, thereby improving major cardiovascular risk factors. A probiotic is defined by FAO/WHO as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host".
The specific strain under investigation, Limosilactobacillus fermentum CRL 1446, demonstrates a singular combination of functional mechanisms that support its potential efficacy in individuals with cardiovascular risk factors. Preclinical assays have shown that administration of the feruloyl esterase-producing strain L. fermentum CRL1446 improves metabolic and oxidative parameters. It is capable of modulating the gut microbiota through the production of beneficial metabolites, enhancing the integrity of the intestinal barrier and reducing bacterial translocation. Furthermore, this strain positively affects lipid metabolism by regulating key enzymes involved in lipid synthesis and degradation. It also exhibits an immunomodulatory action observed in preclinical trials, promoting an anti-inflammatory profile by stimulating regulatory cytokines and decreasing pro-inflammatory mediators. The strain's dual anti-inflammatory and antioxidant effect is linked to an increase in endogenous antioxidant enzymes like superoxide dismutase and glutathione peroxidase, suggesting a capacity to counteract cellular oxidative damage and potentially preserve endothelial function.
Research Question and Hypothesis
The primary research question is whether the consumption of L. fermentum CRL1446 can induce improvements in the metabolic health of adult volunteers with cardiovascular risk factors, potentially preventing or mitigating non-communicable chronic diseases. The working hypothesis is that volunteers who consume L. fermentum CRL 1446 will exhibit significant improvements in their metabolic health compared to those who do not.
Objectives
The general objective is to assess the efficacy of the L. fermentum CRL1446 strain in preventing postprandial glucose peaks, modulating intracellular and plasma inflammatory and redox status, and altering body composition, in volunteers receiving both acute (up to 30 days) and chronic (from 90 days) nutritional interventions.
Specific objectives include:
- Evaluating gastrointestinal symptomatology using the GSRS scale in 80 volunteers during the acute and chronic intervention phases.
- Evaluating postprandial glucose absorption levels and body composition changes in 30 volunteers before and after of consuming 1 capsule/day and 2 capsules/day of L. fermentum CRL1446, compared to placebo. Acute intervention phase.
- Evaluating postprandial glucose absorption levels and body composition changes in 50 volunteers before and after of consuming 1 capsule/day and 2 capsules/day of L. fermentum CRL1446, compared to placebo. Chronic intervention phase.
- Evaluating the modification of biomarkers for oxidative stress, antioxidant defenses, DNA damage, and chronic inflammation in 50 volunteers before and after of consumption (1 capsule/day and 2 capsules/day), compared to placebo. Chronic intervention phase.
- Conditions
- Disbiosis, Obesity, Overweight (BMI > 25), Hypertension (Without Type 2 Diabetes Mellitus), Diabetes (DM), Smoke
- Being tested
- Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU, Placebo (inert excipient)
- Keywords
- Probiótic, Obesity, Cardiovascular Risk
- Medical subject headings
- Dysbiosis, Obesity, Overweight, Hypertension, Diabetes Mellitus, Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFUDietary supplement
Acute phase: After randomization of the groups, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E + 9 CFU (colony-forming units) with their main meal for 30 days. After a 15-day medication-free period, the groups will be crossed over and undergo another 30-day intervention. Following this phase, the acute intervention will be repeated with two capsules daily. Chronic phase: After randomization of the groups, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E + 9 CFU with their main meal for 90 days. After a 15-day drug washout period, the groups will be crossed over, and patients who received a placebo will undergo a 90-day intervention with one daily capsule of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E + 9 CFU with their main meal. Following this phase, the chronic intervention will be repeated with two capsules daily.
Placebo (inert excipient)Dietary supplement
Acute phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 30 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the acute intervention will be repeated with two capsules daily.
Chronic phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 90 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the chronic intervention will be repeated with two capsules daily.
| Study group | Role | What they receive |
|---|---|---|
| Active intervention: Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU | Experimental | Acute phase: After the first randomization, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU (colony-forming units) with their main meal for 30 days. After a 15-day break, the intervention will be repeated with the crossed arms. Once the first intervention is completed, the acute intervention will be repeated with two capsules per day.
Chronic phase: After the second randomization, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU (colony-forming units) with their main meal for 90 days. After a 15-day break, the intervention will be repeated with the crossed arms. Once the first intervention is completed, the chronic intervention will be repeated with two capsules per day. Receives: Dietary Supplement: Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU |
| Placebo (inert excipient) | Placebo comparator | Acute phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 30 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the acute intervention will be repeated with two capsules daily.
Chronic phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 90 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the chronic intervention will be repeated with two capsules daily. Receives: Dietary Supplement: Placebo (inert excipient) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the effects on gastrointestinal well-being and molecular biology by the consumption of Limosilactobacillus fermentum CRL 1446 CONICET 2.20E+9 CFU in volunteers with cardiovascular risk factors.
The researchers propose to thoroughly evaluate the effects on gastrointestinal well-being, glucose metabolism and redox metabolism (oxidative stress, endogenous antioxidant defenses and chronic inflammation) in participants with cardiovascular risk factors, with the aim of determining the impact of the Limosilactobacillus fermentum CRL 1446 CONICET strain on the prevention of cardiovascular diseases.
Measured: 150 days (acute) 390 days (chronic)
Secondary outcomes (6)
Weekly survey on gastrointestinal well-being, tolerance, side effects and/or adverse effects in participants with cardiovascular risk factors, from the acute and chronic consumption of Limosilactobacillus Fermentum CRL 1446 CASASCO CONICET
Gastrointestinal symptoms;
- Health effects
- Tolerance
- Side effects
- Adverse effects.
Method: Using the Gastrointestinal Symptom Rating Scale (GSRS). Units: Score on a scale of 1 to 7 described below on 15 different items
- No discomfort at all
- Minor discomfort
- Mild discomfort
- Moderate discomfort
- Moderately severe discomfort
- Severe discomfort
- Very severe discomfort
Measured: 150 days (acute) 390 days (chronic)
Continuous glucose monitoring by transdermal sensor.
Monitoring biomarkers:
- Glucosa in mg/dL
- Glucose Control Index (GCI) in percentage %.
The Glucose Control Index (GCI) is an estimate of HbA1c based on the average glucose level over the past 10 to 14 days, obtained through continuous glucose monitoring (CGM/Flash). Unlike laboratory-derived HbA1c, the GCI provides short-term information to assess current control and adjust treatment.
Calculation: It is derived directly from the daily average glucose recorded by a sensor, which generally requires at least 5-7 days of data.
Formula: The formula used is: GCI in % = 3.31 + 0.02392 x glucose in mg/dL.
Measured: 150 days (acute) and 390 days (chronic)
Measure of the body composition by impedance analysis
Biomarkers:
- Muscle mass in kg
- Fat mass in kg
Measured: 150 days (acute) and 390 days (chronic)
Measure of the oxidative stress
Biomarkers:
- Lipid peroxidation in nmol/mg of protein.
- Carbonylated proteins in nmol/mg of protein.
- 8(OH)dG in ng/mL.
Measured: 390 days
Measure of the antioxidant defenses
Biomarkers:
- Total Antioxidant Status in mEqTROLOX/mL
- Glutathione in nmol/mg of protein
Measured: 390 days.
Measure of the chronic inflammation
Biomarkers:
- Ferritin in ng/mL
- Haptoglobin in mg/mL
- High-sensitivity PCR in mg/dL
Measured: 390 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2026
- Study start2 Feb 2026
- Primary completion21 Jul 2027 (estimated)
- Study completion21 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for DisbiosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- two-arm, randomized, double-blind, and crossover design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- PINER Pastor Manfredi Winery
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Council of Scientific and Technical Research, Argentina, TIEMPO MEDICO Health Research Center
- Responsible party
- Principal investigator, Raul Francisco Pastor, PINER Pastor Manfredi Winery
- Investigators
- Raul Francisco Pastor, MD, Principal investigator, TIEMPO MEDICO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07530575
- Sponsor's protocol ID
- 26122024
- Status last verified
- May 2026
- First submitted
- 28 Aug 2025
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang Y, Gao Y, He X, Ding S, Gao H. Oral Lactobacillus fermentum CECT5716 in the patients with lactational abscess treated by needle aspiration: The late follow-up of a randomized controlled trial. Medicine (Baltimore). 2022 Jul 1;101(26):e29761. doi: 10.1097/MD.0000000000029761.
PubMed 35777008Arroyo R, Martin V, Maldonado A, Jimenez E, Fernandez L, Rodriguez JM. Treatment of infectious mastitis during lactation: antibiotics versus oral administration of Lactobacilli isolated from breast milk. Clin Infect Dis. 2010 Jun 15;50(12):1551-8. doi: 10.1086/652763.
PubMed 20455694Hegazy SK, El-Bedewy MM. Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis. World J Gastroenterol. 2010 Sep 7;16(33):4145-51. doi: 10.3748/wjg.v16.i33.4145.
PubMed 20806430Songisepp E, Kals J, Kullisaar T, Mandar R, Hutt P, Zilmer M, Mikelsaar M. Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers. Nutr J. 2005 Aug 4;4:22. doi: 10.1186/1475-2891-4-22.
PubMed 16080791Laue C, Papazova E, Pannenbeckers A, Schrezenmeir J. Effect of a Probiotic and a Synbiotic on Body Fat Mass, Body Weight and Traits of Metabolic Syndrome in Individuals with Abdominal Overweight: A Human, Double-Blind, Randomised, Controlled Clinical Study. Nutrients. 2023 Jul 5;15(13):3039. doi: 10.3390/nu15133039.
PubMed 37447365Fabersani E, Russo M, Marquez A, Abeijon-Mukdsi C, Medina R, Gauffin-Cano P. Modulation of intestinal microbiota and immunometabolic parameters by caloric restriction and lactic acid bacteria. Food Res Int. 2019 Oct;124:188-199. doi: 10.1016/j.foodres.2018.06.014. Epub 2018 Jun 5. No abstract available.
PubMed 31466639Abeijon Mukdsi MC, Saavedra L, Gauffin Cano MP, Hebert EM, Medina RB. Draft Genome Sequence of the Feruloyl Esterase-Producing Strain Lactobacillus fermentum CRL1446, a Probiotic for Malnutrition. Genome Announc. 2018 May 24;6(21):e00225-18. doi: 10.1128/genomeA.00225-18.
PubMed 29798910Mukdsi MC, Cano MP, Gonzalez SN, Medina RB. Administration of Lactobacillus fermentum CRL1446 increases intestinal feruloyl esterase activity in mice. Lett Appl Microbiol. 2012 Jan;54(1):18-25. doi: 10.1111/j.1472-765X.2011.03166.x. Epub 2011 Nov 23.
PubMed 22017704Russo M, Fabersani E, Abeijon-Mukdsi MC, Ross R, Fontana C, Benitez-Paez A, Gauffin-Cano P, Medina RB. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice. Nutrients. 2016 Jul 7;8(7):415. doi: 10.3390/nu8070415.
PubMed 27399766Marquez A, Andrada E, Russo M, Bolondi ML, Fabersani E, Medina R, Gauffin-Cano P. Characterization of autochthonous lactobacilli from goat dairy products with probiotic potential for metabolic diseases. Heliyon. 2022 Aug 28;8(9):e10462. doi: 10.1016/j.heliyon.2022.e10462. eCollection 2022 Sep.
PubMed 36091951Paulino do Nascimento LC, Lacerda DC, Ferreira DJS, de Souza EL, de Brito Alves JL. Limosilactobacillus fermentum, Current Evidence on the Antioxidant Properties and Opportunities to be Exploited as a Probiotic Microorganism. Probiotics Antimicrob Proteins. 2022 Oct;14(5):960-979. doi: 10.1007/s12602-022-09943-3. Epub 2022 Apr 25.
PubMed 35467236Russo M , Marquez A , Herrera H , Abeijon-Mukdsi C , Saavedra L , Hebert E , Gauffin-Cano P , Medina R . Oral administration of Lactobacillus fermentum CRL1446 improves biomarkers of metabolic syndrome in mice fed a high-fat diet supplemented with wheat bran. Food Funct. 2020 May 1;11(5):3879-3894. doi: 10.1039/d0fo00730g. Epub 2020 May 18.
PubMed 32421119Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10.
PubMed 24912386Ahmed S, Spence JD. Sex differences in the intestinal microbiome: interactions with risk factors for atherosclerosis and cardiovascular disease. Biol Sex Differ. 2021 May 17;12(1):35. doi: 10.1186/s13293-021-00378-z.
PubMed 34001264Garcia-Fernandez H, Arenas-de Larriva AP, Lopez-Moreno J, Gutierrez-Mariscal FM, Romero-Cabrera JL, Molina-Abril H, Torres-Pena JD, Rodriguez-Cano D, Malagon MM, Ordovas JM, Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, Camargo A. Sex-specific differences in intestinal microbiota associated with cardiovascular diseases. Biol Sex Differ. 2024 Jan 19;15(1):7. doi: 10.1186/s13293-024-00582-7.
PubMed 38243297
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Effects of the Consumption of Limosilactobacillus Fermentum CRL 1446 - CONICET in Volunteers With Cardiovascular Risk Factors
- ClinicalTrials.gov ID
- NCT07530575
- Acronym / sponsor ID
- 26122024
- Conditions
- Disbiosis, Obesity, Overweight (BMI > 25), Hypertension (Without Type 2 Diabetes Mellitus), Diabetes (DM), Smoke
- Keywords
- Probiótic, Obesity, Cardiovascular Risk
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (actual)
- Lead sponsor
- PINER Pastor Manfredi WineryIndustry (pharma, biotech, devices)
- Collaborators
- National Council of Scientific and Technical Research, Argentina, TIEMPO MEDICO Health Research Center
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 21 Jul 2027 (estimated)
- Study completion
- 21 Jul 2027 (estimated)
- First posted
- 15 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study aims to determine if a probiotic called Limosilactobacillus fermentum CRL 1446 can improve the health of people at risk for cardiovascular disease.
The study will be conducted with volunteers who will randomly consume either the probiotic or a placebo (a capsule without the probiotic), without knowing which one they are taking. The researchers will analyze how the probiotic affects blood sugar control, body composition, inflammation, and oxidative stress. The goal is to determine if this beneficial bacterium, by influencing the gut microbiota, could be a new strategy to prevent or mitigate chronic heart diseases.
Detailed description
The clinical study protocol, titled "Biological Effects of Consuming Limosilactobacillus fermentum CRL 1446 CONICET in Volunteers with Cardiovascular Risk Factors" was issued in October 2025 in Version 3.
Rationale and Theoretical Background
The protocol is underpinned by the acknowledgment of the key influence of the gut microbiota on human health, especially concerning cardiovascular risk factors. Data from Argentina's Fourth National Risk Factor Survey indicates a rise in overweight and obesity from 49% in 2005 to 61.6% in 2018. Overweight and obesity, along with dyslipidemia, hypertension, insulin resistance, and chronic inflammation, are closely correlated with imbalances in the gut microbiota, known as dysbiosis, which elevates the risk of cardiovascular diseases. Dysbiosis is characterized by a reduction in bacterial diversity, an increase in pro-inflammatory bacteria, and a decrease in beneficial bacteria that produce short-chain fatty acids.
Nutritional intervention utilizing probiotics presents a promising alternative for modulating the gut microbiota's composition and function, thereby improving major cardiovascular risk factors. A probiotic is defined by FAO/WHO as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host".
The specific strain under investigation, Limosilactobacillus fermentum CRL 1446, demonstrates a singular combination of functional mechanisms that support its potential efficacy in individuals with cardiovascular risk factors. Preclinical assays have shown that administration of the feruloyl esterase-producing strain L. fermentum CRL1446 improves metabolic and oxidative parameters. It is capable of modulating the gut microbiota through the production of beneficial metabolites, enhancing the integrity of the intestinal barrier and reducing bacterial translocation. Furthermore, this strain positively affects lipid metabolism by regulating key enzymes involved in lipid synthesis and degradation. It also exhibits an immunomodulatory action observed in preclinical trials, promoting an anti-inflammatory profile by stimulating regulatory cytokines and decreasing pro-inflammatory mediators. The strain's dual anti-inflammatory and antioxidant effect is linked to an increase in endogenous antioxidant enzymes like superoxide dismutase and glutathione peroxidase, suggesting a capacity to counteract cellular oxidative damage and potentially preserve endothelial function.
Research Question and Hypothesis
The primary research question is whether the consumption of L. fermentum CRL1446 can induce improvements in the metabolic health of adult volunteers with cardiovascular risk factors, potentially preventing or mitigating non-communicable chronic diseases. The working hypothesis is that volunteers who consume L. fermentum CRL 1446 will exhibit significant improvements in their metabolic health compared to those who do not.
Objectives
The general objective is to assess the efficacy of the L. fermentum CRL1446 strain in preventing postprandial glucose peaks, modulating intracellular and plasma inflammatory and redox status, and altering body composition, in volunteers receiving both acute (up to 30 days) and chronic (from 90 days) nutritional interventions.
Specific objectives include:
- Evaluating gastrointestinal symptomatology using the GSRS scale in 80 volunteers during the acute and chronic intervention phases.
- Evaluating postprandial glucose absorption levels and body composition changes in 30 volunteers before and after of consuming 1 capsule/day and 2 capsules/day of L. fermentum CRL1446, compared to placebo. Acute intervention phase.
- Evaluating postprandial glucose absorption levels and body composition changes in 50 volunteers before and after of consuming 1 capsule/day and 2 capsules/day of L. fermentum CRL1446, compared to placebo. Chronic intervention phase.
- Evaluating the modification of biomarkers for oxidative stress, antioxidant defenses, DNA damage, and chronic inflammation in 50 volunteers before and after of consumption (1 capsule/day and 2 capsules/day), compared to placebo. Chronic intervention phase.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- two-arm, randomized, double-blind, and crossover design
| Arm | Type | Receives |
|---|---|---|
| Active intervention: Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU | Experimental | Dietary Supplement: Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFUAcute phase: After the first randomization, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU (colony-forming units) with their main meal for 30 days. After a 15-day break, the intervention will be repeated with the crossed arms. Once the first intervention is completed, the acute intervention will be repeated with two capsules per day. Chronic phase: After the second randomization, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU (colony-forming units) with their main meal for 90 days. After a 15-day break, the intervention will be repeated with the crossed arms. Once the first intervention is completed, the chronic intervention will be repeated with two capsules per day. |
| Placebo (inert excipient) | Placebo comparator | Dietary Supplement: Placebo (inert excipient)Acute phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 30 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the acute intervention will be repeated with two capsules daily. Chronic phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 90 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the chronic intervention will be repeated with two capsules daily. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Blood glucose greater than 100 mg/dl or pharmacological treatment for high blood glucose levels;
- HDL cholesterol < 40 mg/dl in men or < 50 mg/dl in women, or pharmacological treatment for low HDL cholesterol levels;
- Blood triglycerides > 150 mg/dl or pharmacological treatment for high triglyceride levels;
- Waist circumference > 102 cm for men or > 88 cm for women;
- Arterial pressure > 130/85 mmHg;
Key exclusion criteria (2 listed)
- Patients with a history of digestive surgeries, inflammatory bowel disease, patients with gastroenteritis in the last 6 months, cancer patients, patients with rheumatic pathologies, patients with liver disorders, immunological disorders or deficiencies, steatorrhea, antibiotic use in the last 3 months, or anemia of any cause or pregnancy/expectation of becoming pregnant during the study.
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFUAcute phase: After randomization of the groups, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E + 9 CFU (colony-forming units) with their main meal for 30 days. After a 15-day medication-free period, the groups will be crossed over and undergo another 30-day intervention. Following this phase, the acute intervention will be repeated with two capsules daily. Chronic phase: After randomization of the groups, patients will be instructed to take one capsule daily of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E + 9 CFU with their main meal for 90 days. After a 15-day drug washout period, the groups will be crossed over, and patients who received a placebo will undergo a 90-day intervention with one daily capsule of Limosilactobacillus fermentum 1446 CRL CONICET 2.20E + 9 CFU with their main meal. Following this phase, the chronic intervention will be repeated with two capsules daily. | Dietary supplement | Active intervention: Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU |
| Placebo (inert excipient)Acute phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 30 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the acute intervention will be repeated with two capsules daily. Chronic phase: After the initial randomization, patients will be instructed to take one placebo capsule (inert excipient) daily with their main meal for 90 days. After a 15-day break, the intervention will be repeated with the arms crossed. Once the initial intervention is completed, the chronic intervention will be repeated with two capsules daily. | Dietary supplement | Placebo (inert excipient) |
Primary outcome
Evaluation of the effects on gastrointestinal well-being and molecular biology by the consumption of Limosilactobacillus fermentum CRL 1446 CONICET 2.20E+9 CFU in volunteers with cardiovascular risk factors.
Time frame: 150 days (acute) 390 days (chronic)
The researchers propose to thoroughly evaluate the effects on gastrointestinal well-being, glucose metabolism and redox metabolism (oxidative stress, endogenous antioxidant defenses and chronic inflammation) in participants with cardiovascular risk factors, with the aim of determining the impact of the Limosilactobacillus fermentum CRL 1446 CONICET strain on the prevention of cardiovascular diseases.
6 secondary outcomes
Weekly survey on gastrointestinal well-being, tolerance, side effects and/or adverse effects in participants with cardiovascular risk factors, from the acute and chronic consumption of Limosilactobacillus Fermentum CRL 1446 CASASCO CONICET
Time frame: 150 days (acute) 390 days (chronic)
Continuous glucose monitoring by transdermal sensor.
Time frame: 150 days (acute) and 390 days (chronic)
Measure of the body composition by impedance analysis
Time frame: 150 days (acute) and 390 days (chronic)
Measure of the oxidative stress
Time frame: 390 days
Measure of the antioxidant defenses
Time frame: 390 days.
Measure of the chronic inflammation
Time frame: 390 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Background: PubMed 35777008Zhang Y, Gao Y, He X, Ding S, Gao H. Oral Lactobacillus fermentum CECT5716 in the patients with lactational abscess treated by needle aspiration: The late follow-up of a randomized controlled trial. Medicine (Baltimore). 2022 Jul 1;101(26):e29761. doi: 10.1097/MD.0000000000029761.
- Background: PubMed 20455694Arroyo R, Martin V, Maldonado A, Jimenez E, Fernandez L, Rodriguez JM. Treatment of infectious mastitis during lactation: antibiotics versus oral administration of Lactobacilli isolated from breast milk. Clin Infect Dis. 2010 Jun 15;50(12):1551-8. doi: 10.1086/652763.
- Background: PubMed 20806430Hegazy SK, El-Bedewy MM. Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis. World J Gastroenterol. 2010 Sep 7;16(33):4145-51. doi: 10.3748/wjg.v16.i33.4145.
- Background: PubMed 16080791Songisepp E, Kals J, Kullisaar T, Mandar R, Hutt P, Zilmer M, Mikelsaar M. Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers. Nutr J. 2005 Aug 4;4:22. doi: 10.1186/1475-2891-4-22.
- Background: PubMed 37447365Laue C, Papazova E, Pannenbeckers A, Schrezenmeir J. Effect of a Probiotic and a Synbiotic on Body Fat Mass, Body Weight and Traits of Metabolic Syndrome in Individuals with Abdominal Overweight: A Human, Double-Blind, Randomised, Controlled Clinical Study. Nutrients. 2023 Jul 5;15(13):3039. doi: 10.3390/nu15133039.
- Background: PubMed 31466639Fabersani E, Russo M, Marquez A, Abeijon-Mukdsi C, Medina R, Gauffin-Cano P. Modulation of intestinal microbiota and immunometabolic parameters by caloric restriction and lactic acid bacteria. Food Res Int. 2019 Oct;124:188-199. doi: 10.1016/j.foodres.2018.06.014. Epub 2018 Jun 5. No abstract available.
- Background: PubMed 29798910Abeijon Mukdsi MC, Saavedra L, Gauffin Cano MP, Hebert EM, Medina RB. Draft Genome Sequence of the Feruloyl Esterase-Producing Strain Lactobacillus fermentum CRL1446, a Probiotic for Malnutrition. Genome Announc. 2018 May 24;6(21):e00225-18. doi: 10.1128/genomeA.00225-18.
- Background: PubMed 22017704Mukdsi MC, Cano MP, Gonzalez SN, Medina RB. Administration of Lactobacillus fermentum CRL1446 increases intestinal feruloyl esterase activity in mice. Lett Appl Microbiol. 2012 Jan;54(1):18-25. doi: 10.1111/j.1472-765X.2011.03166.x. Epub 2011 Nov 23.
- Background: PubMed 27399766Russo M, Fabersani E, Abeijon-Mukdsi MC, Ross R, Fontana C, Benitez-Paez A, Gauffin-Cano P, Medina RB. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice. Nutrients. 2016 Jul 7;8(7):415. doi: 10.3390/nu8070415.
- Background: PubMed 36091951Marquez A, Andrada E, Russo M, Bolondi ML, Fabersani E, Medina R, Gauffin-Cano P. Characterization of autochthonous lactobacilli from goat dairy products with probiotic potential for metabolic diseases. Heliyon. 2022 Aug 28;8(9):e10462. doi: 10.1016/j.heliyon.2022.e10462. eCollection 2022 Sep.
- Background: PubMed 35467236Paulino do Nascimento LC, Lacerda DC, Ferreira DJS, de Souza EL, de Brito Alves JL. Limosilactobacillus fermentum, Current Evidence on the Antioxidant Properties and Opportunities to be Exploited as a Probiotic Microorganism. Probiotics Antimicrob Proteins. 2022 Oct;14(5):960-979. doi: 10.1007/s12602-022-09943-3. Epub 2022 Apr 25.
- Background: PubMed 32421119Russo M , Marquez A , Herrera H , Abeijon-Mukdsi C , Saavedra L , Hebert E , Gauffin-Cano P , Medina R . Oral administration of Lactobacillus fermentum CRL1446 improves biomarkers of metabolic syndrome in mice fed a high-fat diet supplemented with wheat bran. Food Funct. 2020 May 1;11(5):3879-3894. doi: 10.1039/d0fo00730g. Epub 2020 May 18.
- Argentina's Fourth National Risk Factor Survey 2018Link provided by the sponsor.
Related trials for Disbiosis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Enrolling by invitationPhase 2
Herbal Supplement (Biocidin REMOVE) for Bacterial Overgrowth in Irritable Bowel Syndrome
Irritable Bowel Syndrome (IBS), Small Intestinal Bacterial Overgrowth Syndrome (SIBO)
RecruitingObservational study
Effects Of Periodontal Therapy In Patients With Inflammatory Bowel Disease
Periodontal Diseases, IBD
Recruiting
Effect of a Probiotic or Postbiotic on Gut Microbiome During Antibiotic Treatment
Microbiome
RecruitingObservational study
Metabolic and Functional Study of γδ T Cells in Critically Ill Patients
Sepsis, Critical Illness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raul Francisco Pastor, MD principal investigator
TIEMPO MEDICO
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Limosilactobacillus fermentum 1446 CRL CONICET 2.20E+9 CFU in people with Disbiosis and Obesity, run by PINER Pastor Manfredi Winery at 2 sites in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the effects on gastrointestinal well-being and molecular biology by the consumption of Limosilactobacillus fermentum CRL 1446 CONICET 2.20E+9 CFU in volunteers with cardiovascular risk factors. (time frame: 150 days (acute) 390 days (chronic)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07530575, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.