A Pilot Study to Evaluate the Systemic Effect of Oral Supplementation With AM3 in Patients With Metabolic Syndrome.

Metabolic Syndrome Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Systemic Effect on Immunoinflammatory and Metabolic Status of an Oral Supplementation With AM3 in Patients With Metabolic Syndrome.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06158152
• Other study ID #: P20110a
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 20, 2024
• Est. completion date: February 1, 2025

Study information

• Verified date: January 2024
• Source: Industrial Farmacéutica Cantabria, S.A.
• Contact: Ana López-Ballesteros
• Phone: +34 671778847
• Email: ana.lopez[@]cantabrialabs.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this pilot study is to learn about the effect of the nutritional supplementation based on AM3 in combination with probiotics on imflammatory and metabolic mediators in adult subjects diagnosed with metabolic syndrome.

The hypothesis the investigators are testing focuses on the fact that the continued use of the nutritional supplement with AM3 and probiotics is capable of minimizing the risk factors associated with metabolic syndrome, by reducing the development of the derived chronic pathologies.

A total of 48 subjects with a diagnosis of metabolic syndrome is planned to be recruited from two investigational sites in the Comunity of Madrid (Spain). These subjects will be randomized into three treatment groups (active, placebo, and control). The dosage will be of 2 capsules/day in a single intake in the morning for 12 weeks. Two interventional visits are planned to be performed: at baseline and at week 12.

Description:

This is a randomized, double-blind, placebo-controlled, pilot study. The primay objective is to evaluate the systemic effect of this new nutritional supplement with AM3 and probiotics on the immuno-inflammatory and metabolic status against metabolic syndrome.

The secondary objectives are:

1. To determine the efficacy of the administration of a new food supplement for MS through the improvement of biochemical variables.

2. To evaluate the efficacy of the administration of a new dietary supplement on the impact on body composition parameters.

3. To evaluate the patient's quality of life.

Adult subjects (aged between 18 and 65 years) will randomly be assigned into one of these three treatment groups:

• Active: patients who will receive the study treatment, consisting of the combination of AM3 and the probiotic SynBalance Metsyn.

• Placebo: patients who will receive placebo (starch capsules), with no active ingredient.

• Control: patients to be treated with AM3 capsules alone (no probiotics).

Interventions performed at time 0 and 12 weeks, are carried out to measure parameters such as the following: body composition data (weight, BMI), blood pressure, fasting glucose and insulin levels, monocyte and NK-cell populations, liver enzyme levels, urine sediment, etc.

Finally, a subjective questionnaire is used to evaluate the patients' quality of life before and after treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: February 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Men or women aged 18-65 years at the time of signing the informed consent form

2. Metabolic syndrome diagnosis: central obesity, elevation of blood glucose by =100 mg/dl, glycosylated hemoglobin between 5.7 and 6.4%, low HDL cholesterol levels < 40 mg/dl in men and < 50 mg/dl in women, and high levels of triglycerides, being higher than 150 mg/dl

3. Patient without treatment with metformin or if on stable treatment, with no changes in the dosage, for at least 3 months

4. Hypolipidemic treatment with statins unchanged for the last 6 months

5. Treatment with antihypertensives (other than beta-blockers) unchanged for the last 6 months

6. Follow the lifestyle recommendations: nutritional, physical exercise, as recommended by your specialist

Exclusion Criteria:

1. Smokers or with history of alcoholism or drug abuse

2. Have started treatment with metformin or have modified its dosage in the last 3 months

3. To have hypertriglyceridemia

4. Uncontrolled arterial hypertension

5. To have undergone bariatric surgery within the last two years

6. Diagnosis of chronic diseases and metabolic complications (diabetes, myocardial infarction, renal disease, COPD, cardiovascular disease or thyroid disease)

7. Presence of renal, respiratory or cardiac insufficiency

8. Presence of chronic obstructive disease, inflammatory bowel disease, intestinal malabsorption syndrome, systemic autoimmune diseases, rheumatoid arthritis, spondyloarthritis, psoriasis and chronic inflammatory skin diseases

9. Active or chronic infections

10. Psychosis

11. Disease-related malnutrition

12. Endocrinologic diseases with manifestations in pituitary, adrenal or thyroid function

13. Immunosuppressive treatment in the last 3 months

14. Being breast-feeding, pregnant or intending to become pregnant

Related Conditions & MeSH terms

• Metabolic Syndrome
• Syndrome

Intervention

Dietary Supplement:
• AM3 + Probiotic
Two capsules daily in the morning during 12 weeks. The capsule contains the mixture of AM3 Technology and probiotic SynBalance Metsyn.
• Placebo
Two capsules daily in the morning during 12 weeks. The capsule contains starch.
• AM3
Two capsules daily in the morning during 12 weeks. The capsule contains AM3 Technology.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Industrial Farmacéutica Cantabria, S.A.

References & Publications (25)

Albillos A, de la Hera A, Gonzalez M, Moya JL, Calleja JL, Monserrat J, Ruiz-del-Arbol L, Alvarez-Mon M. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology. 2003 Jan;37(1):208-17. — View Citation

Alvarez-Mon M, Ortega MA, Gasulla O, Fortuny-Profitos J, Mazaira-Font FA, Saurina P, Monserrat J, Plana MN, Troncoso D, Moreno JS, Munoz B, Arranz A, Varona JF, Lopez-Escobar A, Barco AA. A Predictive Model and Risk Factors for Case Fatality of COVID-19. — View Citation

Alvarez-Mon MA, Gomez-Lahoz AM, Orozco A, Lahera G, Diaz D, Ortega MA, Albillos A, Quintero J, Auba E, Monserrat J, Alvarez-Mon M. Expansion of CD4 T Lymphocytes Expressing Interleukin 17 and Tumor Necrosis Factor in Patients with Major Depressive Disorde — View Citation

Alvarez-Mon MA, Ortega MA, Garcia-Montero C, Fraile-Martinez O, Lahera G, Monserrat J, Gomez-Lahoz AM, Molero P, Gutierrez-Rojas L, Rodriguez-Jimenez R, Quintero J, Alvarez-Mon M. Differential malondialdehyde (MDA) detection in plasma samples of patients — View Citation

Borchers A, Pieler T. Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs. Genes (Basel). 2010 Nov 18;1(3):413-26. doi: 10.3390/genes1030413. — View Citation

Brieva A, Guerrero A, Alonso-Lebrero JL, Pivel JP. Immunoferon, a glycoconjugate of natural origin, inhibits LPS-induced TNF-alpha production and inflammatory responses. Int Immunopharmacol. 2001 Oct;1(11):1979-87. doi: 10.1016/s1567-5769(01)00125-4. — View Citation

Cicero AFG, Fogacci F, Bove M, Giovannini M, Borghi C. Impact of a short-term synbiotic supplementation on metabolic syndrome and systemic inflammation in elderly patients: a randomized placebo-controlled clinical trial. Eur J Nutr. 2021 Mar;60(2):655-663 — View Citation

Donath MY, Dinarello CA, Mandrup-Poulsen T. Targeting innate immune mediators in type 1 and type 2 diabetes. Nat Rev Immunol. 2019 Dec;19(12):734-746. doi: 10.1038/s41577-019-0213-9. Epub 2019 Sep 9. — View Citation

Francisco V, Ruiz-Fernandez C, Pino J, Mera A, Gonzalez-Gay MA, Gomez R, Lago F, Mobasheri A, Gualillo O. Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases. Biochem Pharmacol. 2019 Jul;165:196-206. doi: 10.1016/j.bcp.2019.0 — View Citation

Grandl G, Wolfrum C. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Semin Immunopathol. 2018 Feb;40(2):215-224. doi: 10.1007/s00281-017-0666-5. Epub 2017 Dec 5. — View Citation

Guerrero A, Brieva A, Pivel JP. A new method for radioiodination of polysaccharides and its use in biodistribution studies of an immunomodulating glycoconjugate (Immunoferon). Methods Find Exp Clin Pharmacol. 2000 Oct;22(8):621-5. doi: 10.1358/mf.2000.22. — View Citation

Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019 Jul 16;11(7):1613. doi: 10.3390/nu11071613. — View Citation

King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol. 2008 Aug;79(8 Suppl):1527-34. doi: 10.1902/jop.2008.080246. — View Citation

Lario M, Munoz L, Ubeda M, Borrero MJ, Martinez J, Monserrat J, Diaz D, Alvarez-Mon M, Albillos A. Defective thymopoiesis and poor peripheral homeostatic replenishment of T-helper cells cause T-cell lymphopenia in cirrhosis. J Hepatol. 2013 Oct;59(4):723- — View Citation

Majano P, Alonso-Lebrero JL, Janczyk A, Martin-Vichez S, Molina-Jimenez F, Brieva A, Pivel JP, Gonzalez S, Lopez-Cabrera M, Moreno-Otero R. AM3 inhibits LPS-induced iNOS expression in mice. Int Immunopharmacol. 2005 Jul;5(7-8):1165-70. doi: 10.1016/j.inti — View Citation

Mendrick DL, Diehl AM, Topor LS, Dietert RR, Will Y, La Merrill MA, Bouret S, Varma V, Hastings KL, Schug TT, Emeigh Hart SG, Burleson FG. Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic. Toxicol Sci. 2018 Mar 1;162(1):36-42. doi: — View Citation

Monserrat J, Asunsolo A, Gomez-Lahoz A, Ortega MA, Gasalla JM, Gasulla O, Fortuny-Profitos J, Mazaira-Font FA, Teixido Roman M, Arranz A, Sanz J, Munoz B, Arevalo-Serrano J, Rodriguez JM, Martinez-A C, Balomenos D, Alvarez-Mon M. Impact of the Innate Infl — View Citation

Ortega del Alamo P, Rivera Rodriguez T, Sanz Fernandez R. [The effect of AM3 in the resolution of otitis media with effusion (OME) in paediatric patients]. Acta Otorrinolaringol Esp. 2005 Jan;56(1):1-5. doi: 10.1016/s0001-6519(05)78561-7. Spanish. — View Citation

Ortega MA, Fraile-Martinez O, Garcia-Montero C, Alvarez-Mon MA, Gomez-Lahoz AM, Albillos A, Lahera G, Quintero J, Monserrat J, Guijarro LG, Alvarez-Mon M. An Updated View of the Importance of Vesicular Trafficking and Transport and Their Role in Immune-Me — View Citation

Prieto A, Reyes E, Bernstein ED, Martinez B, Monserrat J, Izquierdo JL, Callol L, de LUCAS P, Alvarez-Sala R, Alvarez-Sala JL, Villarrubia VG, Alvarez-Mon M. Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are r — View Citation

Remely M, Hippe B, Zanner J, Aumueller E, Brath H, Haslberger AG. Gut Microbiota of Obese, Type 2 Diabetic Individuals is Enriched in Faecalibacterium prausnitzii, Akkermansia muciniphila and Peptostreptococcus anaerobius after Weight Loss. Endocr Metab I — View Citation

Serrano-Gomez D, Martinez-Nunez RT, Sierra-Filardi E, Izquierdo N, Colmenares M, Pla J, Rivas L, Martinez-Picado J, Jimenez-Barbero J, Alonso-Lebrero JL, Gonzalez S, Corbi AL. AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC- — View Citation

Varela J, Navarro Pico ML, Guerrero A, Garcia F, Gimenez Gallego G, Pivel JP. Identification and characterization of the peptidic component of the immunomodulatory glycoconjugate Immunoferon. Methods Find Exp Clin Pharmacol. 2002 Oct;24(8):471-80. doi: 10 — View Citation

Vega-Robledo GB, Rico-Rosillo MG. [Adipose tissue: immune function and alterations caused by obesity]. Rev Alerg Mex. 2019 Jul-Sep;66(3):340-353. doi: 10.29262/ram.v66i3.589. Spanish. — View Citation

Wang Q, Wu H. T Cells in Adipose Tissue: Critical Players in Immunometabolism. Front Immunol. 2018 Oct 30;9:2509. doi: 10.3389/fimmu.2018.02509. eCollection 2018. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in serum cytokines.	Circulating cytokine levels will be determined at baseline and at week 12 to assess the effect on inflammatory mediators.	Baseline and week 12
Secondary	Change in monocytes and natural killer cells levels.	Serum monocytes and natural killers cells will be determined at baseline and week 12 to assess the effect on inflammatory status and oxidative stress.	Baseline and week 12
Secondary	Change in serum uric acid.	Uric acid will be analized to assess the effect on inflammatory and metabolic mediators. These results will be displayed in the results data table.	Baseline and week 12
Secondary	Change in serum sodium.	sodium will be analized to assess the effect on inflammatory and metabolic mediators. These results will be displayed in the results data table.	Baseline and week 12
Secondary	Change in serum potasium.	potassium will be analized to assess the effect on inflammatory and metabolic mediators. These results will be displayed in the results data table.	Baseline and week 12
Secondary	Change in serum bilirrubin.	Bilirrubin will be analized to assess the effect on inflammatory and metabolic mediators. These results will be displayed in the results data table.	Baseline and week 12
Secondary	Change in serum lipids	Serum lipids will be determined at baseline and at week 12 to assess the effect on metabolic parameters.	Baseline and week 12
Secondary	Change in serum glucose	Fasting blood glucose levels will be analized to assess the effect on inflammatory and metabolic mediators.	Baseline and week 12
Secondary	Change in blood pressure	Blood pressure (Diastolic and systolic) [mmHg] will be determined at baseline and after 12 weeks of study treatment.	Baseline and week 12.
Secondary	Change in waist circumference	Waist circumference [cm] will be obtained at baseline and at week 12 to assess the efficacy on body composition.	Baseline and week 12
Secondary	Change in hip circumference	Hip circumference [cm] will be obtained at baseline and at week 12 to assess the efficacy on body composition.	Baseline and week 12
Secondary	Change in weight	Weight [Kg] will be obtained at baseline and at week 12 to assess the efficacy on body composition. These results will be displayed in the results data table.	Baseline and week 12
Secondary	Change in body mass index	BMI [Kg/m2] will be obtained at baseline and at week 12 to assess the efficacy on body composition. These results will be displayed in the results data table.	Baseline and week 12
Secondary	Change in total body fat content	Total body fat content will be measured at baseline and at week 12 using electrical bioimpedance.	Baseline and week 12
Secondary	Change in patient's quality of life, assessed by the SF-12v2 score.	This is a health-related quality-of-life questionnaire, consisting of 12 questions that measure eight health domains to assess physical and mental health. Physical health-related domains include General Health (GH), Physical Functioning (PF), Role Physical (RP), and Body Pain (BP). This score will be determined at baseline and at week 12.; Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	Baseline and week 12

External Links

•   Immunopathogenesis of aging: the impairment of innate immunity and its impact on specific immunity. Restoration by AM3.
•   Inflammation and insulin resistance: mechanisms for the endothelial dysfunction development and atherosclerosis.