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

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.

Overview

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.

Detailed 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 75 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.

Interventions

• 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.
• Dietary supplement Placebo
  Two capsules daily in the morning during 12 weeks. The capsule contains starch.
• Dietary supplement AM3
  Two capsules daily in the morning during 12 weeks. The capsule contains AM3 Technology.

Primary outcome measures

• Change in serum cytokines. [Time frame: Baseline and week 12]

Secondary outcome measures (12)

• Change in monocytes and natural killer cells levels. [Time frame: Baseline and week 12]
• Change in serum uric acid. [Time frame: Baseline and week 12]
• Change in serum sodium. [Time frame: Baseline and week 12]
• Change in serum potasium. [Time frame: Baseline and week 12]
• Change in serum bilirrubin. [Time frame: Baseline and week 12]
• Change in serum lipids [Time frame: Baseline and week 12]
• Change in serum glucose [Time frame: Baseline and week 12]
• Change in blood pressure [Time frame: Baseline and week 12.]
• Change in waist circumference [Time frame: Baseline and week 12]
• Change in hip circumference [Time frame: Baseline and week 12]
• Change in weight [Time frame: Baseline and week 12]
• Change in body mass index [Time frame: Baseline and week 12]

Eligibility criteria

Inclusion criteria

• Men or women aged 18-75 years at the time of signing the informed consent form.
• Diagnosis of metabolic syndrome, defined as: 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.
• If the patient is being treated with metformin, lipid-lowering treatment with statins or treatment with antihypertensives, he/she must have a stable dose at the time of inclusion.

Exclusion criteria

• Smokers or with history of alcoholism or drug abuse .
• To have hypertriglyceridemia (> 500 mg/dL).
• Uncontrolled arterial hypertension, as per investigator's criteria.
• To have undergone bariatric surgery over the last 24 months that according to investigator's criteria, this might interfere with his/her participation in the study.
• Diagnosis of chronic diseases that according to investigator's criteria, this might interfere with his/her participation in the study.
• Presence of renal insufficiency (glomerular filtration rate below 30 ml/minute).
• Presence of severe respiratory insufficiency (PaO2 less than 60 mmHg or PaCO2 greater than 50 mmHg).
• Presence of heart failure (LVEF <30% and RVEF <35%).
• Presence of the following diseases in an unstable manner, according to the investigator's criteria: chronic obstructive disease, inflammatory bowel disease, intestinal malabsorption syndrome, systemic autoimmune diseases, rheumatoid arthritis, spondyloarthritis, psoriasis, and chronic inflammatory skin diseases.
• Active or chronic severe unstable infections that, in medical criteria, may interfere with patients' safety.
• Disease-related malnutrition.
• Endocrinologic unestable or uncontrolled diseases that in medical criteria, present with manifestations in pituitary, adrenal or thyroid function.
• Immunosuppressive or corticosteroid treatment in the last 3 months.
• Treatment with semaglutide and tirzepatide.
• Pregnant women (or intending to become pregnant) or breast-feeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Supportive care

Study locations

Spain · 2 centers

• Hospital Universitario Infanta Leonor — Madrid
• Hospital Universitario Príncipe de Asturias — Madrid

Publications

• 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.2019.03.030. Epub 2019 Mar 22. PMID 30910694
• 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: 10.1093/toxsci/kfx233. PMID 29106690
• 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. PMID 29209827
• 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. PMID 30459770
• 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.2000.22.8.802273. PMID 11256233
• 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. PMID 31606018
• 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: 10.1358/mf.2002.24.8.705066. PMID 12500425
• 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. PMID 15747716

Identifiers

NCT: NCT06158152 · P20110a

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗