Probiotics for Vascular Inflammation in Metabolic Syndrome (PROMISE)

• ClinicalTrials.gov Identifier: NCT03719794
• Recruitment Status: Completed
• First Posted: October 25, 2018
• Last Update Posted: January 14, 2021
• Sponsor: Montreal Heart Institute
• Collaborator: Lallemand Health Solutions
• Information provided by (Responsible Party): Montreal Heart Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metabolic Syndrome	Dietary Supplement: Probiotic supplement; Dietary Supplement: Placebo supplement	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Probiotics for Vascular Inflammation in Metabolic Syndrome (PROMISE): a 12-Week Pilot Study, Randomized,Double-Blinded, Placebo-Controlled Trial
• Actual Study Start Date: April 16, 2018
• Actual Primary Completion Date: October 1, 2020
• Actual Study Completion Date: October 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or 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.

Secondary Outcome Measures :

1. Mesure of High-sensitivity C-reactive protein (hs-CRP) a systemic inflammatory marker. [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   Change with hs-CRP
2. Mesure of Tumor necrosis factor alpha (TNF-α) a systemic inflammatory marker. [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   Change with TNF-α
3. Mesure of Matrix metallopeptidase 9 (MMP-9) [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   Change with MMP-9
4. Cognitive function at rest by a standard pen-paper battery test. [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   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.
5. Intestinal microbiota community composition [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   To evaluate the impact on intestinal microbiota community composition

Other Outcome Measures:

1. Mesure of blood fasting glucose [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   Change in fasting glucose
2. Mesure of blood Serum lipids [ Time Frame: At baseline and following 12 weeks of probiotic supplementation or placebo. ]
   Change in serum lipids

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Canada, Quebec

Cardiovascular Prevention and Rehabilitation Center

Montreal, Quebec, Canada, H1T 1N6

Sponsors and Collaborators

Montreal Heart Institute

Lallemand Health Solutions

Investigators

• Principal Investigator: Anil Nigam, MD; Montreal Heart Institute

More Information

• Responsible Party: Montreal Heart Institute
• ClinicalTrials.gov Identifier: NCT03719794
• Other Study ID Numbers: 2016-2038
• First Posted: October 25, 2018
• Last Update Posted: January 14, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Metabolic Syndrome; Syndrome; Inflammation; Disease; Pathologic Processes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases