Clinical trial NCT03719794: Probiotics for Vascular Inflammation in Metabolic Syndrome
Official title: Probiotics for Vascular Inflammation in Metabolic Syndrome (PROMISE): a 12-Week Pilot Study, Randomized,Double-Blinded, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: Lallemand Health Solutions
First posted: 2018-10-25
Enrollment: 24
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
Secondary outcomes:
measure: Mesure of High-sensitivity C-reactive protein (hs-CRP) a systemic inflammatory marker.
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
measure: Mesure of Tumor necrosis factor alpha (TNF-α) a systemic inflammatory marker.
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
measure: Mesure of Matrix metallopeptidase 9 (MMP-9)
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
measure: Cognitive function at rest by a standard pen-paper battery test.
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
measure: Intestinal microbiota community composition
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
Other outcomes:
measure: Mesure of blood fasting glucose
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
measure: Mesure of blood Serum lipids
timeFrame: At baseline and following 12 weeks of probiotic supplementation or placebo.
Locations:
city: Montreal
country: Canada
facility: Cardiovascular Prevention and Rehabilitation Center
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Anil Nigam, MD
role: PRINCIPAL_INVESTIGATOR
References: