Probiotics for Vascular Inflammation in Metabolic Syndrome (PROMISE)

Probiotics for Vascular Inflammation in Metabolic Syndrome (PROMISE): a 12-Week Pilot Study, Randomized,Double-Blinded, Placebo-Controlled Trial

Subjects with metabolic syndrome are known to possess chronic low-level inflammation. Furthermore, such individuals are at risk of developing atherosclerosis in coronary and other vascular beds. In particular, subjects with metabolic syndrome, prediabetes and type II diabetes mellitus were shown to possess vascular inflammation in carotid atherosclerosis as demonstrated using FDG-PET. In the current pilot proposal, the investigators wish to study the impact of 3-month probiotic supplementation on vascular and systemic inflammation in subjects with metabolic syndrome in the context of a randomized, placebo-controlled, pilot trial.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Probiotic supplement; Dietary supplement: Placebo supplement

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 1N6
      • Cardiovascular Prevention and Rehabilitation Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female age > 50 years
• Presence of MetS as defined according to recent updated criteria (13): Presence of at least three of five criteria, namely abdominal obesity (waist circumference cut-off) depending on the recently published ethnic-based variations (14), triglycerides > 1.70 mmol/l, decreased HDL-cholesterol (< 1.0 mmol/l in men and < 1.3 mmol/l in women), systolic blood pressure > 130 mmHg or diastolic blood pressure > 85 mmHg, and FPG > 5.6 mmol/l.
• Willingness to complete questionnaires, records, and diaries associated with the study and to complete all clinic visits.
• Willingness to discontinue consumption of fermented foods or probiotics (e.g. yoghourts, with live, active cultures or supplements).
• Able to provide informed consent.

Exclusion Criteria:

• Concurrent consumption of fermented foods or probiotics (e.g. yoghourts, with live, active cultures or supplements). Subjects will be eligible for participation, however, after a two-week washout period
• Overt or documented vascular disease (coronary heart disease, cerebrovascular disease, or peripheral vascular disease).
• Participants suffering from dementia (mini mental state examination) or depression (geriatric depression scale).
• Concurrent statin therapy. (Statins have been shown to reduce vascular inflammation as measured by FDG-PET-see section 9.1).
• Color blind
• Concurrent antibiotic therapy. However, screened participants would be eligible to participate two weeks after completing their course of antibiotics (wash-out period).
• Known to be pregnant or breast-feeding or planning on becoming pregnant in the next 18 months.
• Women of childbearing potential not using effective contraception. Acceptable methods of birth control includes:
• Hormonal contraceptives including combined oral contraceptives, hormone birth control patch, vaginal contraceptive ring, injectable contraceptives, or hormonal implants;
• Intrauterine devices (IUD) or Intrauterine system (IUS);
• Tubal ligation;
• Vasectomy of partner;
• Double barrier method (use of physical barrier by both partners, e.g. male condom and diaphragm, male condom and cervical cap).
• Positive pregnancy test in women of childbearing potential.
• Allergy to milk, soy, or yeast.
• Use of another investigational product within 3 months of the screening visit.
• Claustrophobia
• Patient with pacemaker
• Patient with BMI greater than 40 kg/m2
• Immune disorder.
• Drug and alcohol abuse
• Current use of NSAIDs
• Liver and kidney disorders
• Bleeding/blood disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotics arm; The active comparator arm will be of a 12-week probiotic supplement regimen (one capsule daily, containing 20 x 109 CFU of Bifidobacterium animalis ssp. Lactis Lafti®B94 and Lactobacillus plantarum R1012)	Dietary supplement: Probiotic supplement; Probiotic supplement once daily (xyz) for 12 weeks
Placebo Comparator: Placebo arm; The placebo comparator arm will be of a 12-week placebo supplement regimen.	Dietary supplement: Placebo supplement; Placebo supplement once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is to evaluate the change on vascular inflammation (measured by FDG-PET), so as to test the hypothesis that probiotic treatment reduces vascular inflammation in comparison to placebo.	PET-CT scan of the carotid arteries and ascending thoracic aorta will be performed 2 hours post I.V. The participant will be injected with 18F-FDG.	At baseline and following 12 weeks of probiotic supplementation or placebo.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mesure of High-sensitivity C-reactive protein (hs-CRP) a systemic inflammatory marker.	Change with hs-CRP	At baseline and following 12 weeks of probiotic supplementation or placebo.
Mesure of Tumor necrosis factor alpha (TNF-α) a systemic inflammatory marker.	Change with TNF-α	At baseline and following 12 weeks of probiotic supplementation or placebo.
Mesure of Matrix metallopeptidase 9 (MMP-9)	Change with MMP-9	At baseline and following 12 weeks of probiotic supplementation or placebo.
Cognitive function at rest by a standard pen-paper battery test.	Cognitive functions will be measured at rest with a pen-paper battery test by a neuropsychologist. The investigators will measure change of score to the cognitive tests.	At baseline and following 12 weeks of probiotic supplementation or placebo.
Intestinal microbiota community composition	To evaluate the impact on intestinal microbiota community composition	At baseline and following 12 weeks of probiotic supplementation or placebo.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mesure of blood fasting glucose	Change in fasting glucose	At baseline and following 12 weeks of probiotic supplementation or placebo.
Mesure of blood Serum lipids	Change in serum lipids	At baseline and following 12 weeks of probiotic supplementation or placebo.

Collaborators and Investigators

• Sponsor: Montreal Heart Institute
• Collaborators: Lallemand Health Solutions
• Investigators: Principal Investigator: Anil Nigam, MD, Montreal Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (Actual): October 25, 2018

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Inflammation; Metabolic Syndrome
• Other Study ID Numbers: 2016-2038

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No