Phase 1: To assess the safety of carotenoid-producing Bacillus strain PD01 administered orally once daily in healthy volunteers for 14 consecutive days. Phase 2: To determine the effects of daily administration of a carotenoid-producing Bacillus…
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Source
Brief title
Condition
- Other condition
Synonym
Health condition
Risicofactoren voor cardiovasculaire ziekten; systemische laaggradige inflammatie; verstoringen intestinale barrierefunctie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 1: The primary objective is safety, measured by blood parameters and
questionnaires.
Phase 2: The primary efficacy parameter of the study is lipid peroxidation, as
assessed by urinary concentration of F2-isoprostanes.
Secondary outcome
Phase 2:
Secondary endpoints entail the evaluation of effects of daily administration of
PD01 on lipid peroxidation (blood measurements), low-grade inflammation (blood
and fecal measurements), platelet aggregation (blood measurements), glucose /
insulin metabolism (blood measurements), lipid profile (blood measurements),
blood pressure & heart rate, body composition, microbiota composition and
functioning (fecal measurements), gut barrier function (blood and fecal
measurements, urine collection), bioavailability (blood measurements) and
tolerance and digestive (dys)comfort.
Background summary
Overweight and obesity are associated with the metabolic syndrome (MetS), which
is associated with an increased risk of developing cardiovascular disease (CVD)
and diabetes (DM). Furthermore, overweight is associated with an altered
intestinal microbiota and an increased intestinal permeability. This decreased
barrier function may lead to translocation of intestinal bacteria and/or
lipopolysaccharides into the circulation, contributing to chronic low-grade
systemic inflammation. This chronic inflammation is thought to play an
important role in the development of cardiovascular diseases. Over the last
decade, MetS has progressively become a major worldwide public health problem.
Scientifically substantiated effective dietary interventions to improve
cardiometabolic and intestinal health are needed. Supplementation of a
carotenoid-producing Bacillus strain PD01 to those at risk may have beneficial
effects on microbiota composition and functioning, intestinal barrier function
and biomarkers for cardiovascular health.
As the proposed intervention study involves the first-time administration of
strain PD01 to humans, the first study phase (phase 1) will consist of the
additional safety evaluation of PD01 in healthy human beings. In case a clear
safety profile of PD01 is seen in this first part of the study, in confirmation
of the available in vitro and animal safety data, we will continue to conduct a
second phase (phase 2) which consists of a 6-week efficacy trial. Efficacy of
PD01 on cardiovascular health, microbiota composition and functioning and
intestinal barrier function in healthy, overweight subjects will be tested in a
randomized placebo-controlled parallel design.
Study objective
Phase 1: To assess the safety of carotenoid-producing Bacillus strain PD01
administered orally once daily in healthy volunteers for 14 consecutive days.
Phase 2: To determine the effects of daily administration of a
carotenoid-producing Bacillus strain PD01 over a 6-wk period on cardiovascular
health biomarkers, microbiota composition and functioning and intestinal
barrier function in overweight subjects.
Study design
Phase 1: This is an open-label study.
Phase 2: This is a randomized, double-blind, placebo-controlled study with
parallel design.
Intervention
Phase 1:Participants will receive one daily dose of PD01 for a period of 14
days. The study product will be supplied in a sachet and this has to be
dissolved in a glass of 150 mL whole milk before ingestion.
Phase 2: Participants will be randomly assigned to one of the intervention
groups. One group will receive one daily dose of PD01 while the other group
receives identical looking placebo for a period of 6 weeks. The study product
will be supplied in a sachet and this has to be dissolved in a glass of 150 mL
whole milk before ingestion.
Study burden and risks
Phase 1:
There are several burdens volunteers can experience during the study period.
After inclusion, study procedures will take maximally 7 hours for each of the
subjects. According to the schedule, subjects will visit the MUMC+ at 3
occasions. Subjects will have to take PD01 supplements once daily for 14
consecutive days. Subjects will have to follow a documented dietary and health
regimen, and are not allowed to use alcohol or perform strenuous physical
exercise during and 2 days prior to the test days. Study participants will
undergo blood pressure, heart rate and anthropometric measurements.
Furthermore, a maximum total of 64 mL blood will be sampled during the study
visits by venipuncture. This may lead to small and transitory hematoma/bruises
at the site of the venipuncture. Furthermore, they have to fill in
questionnaires and a diary.
Phase 2:
There are several burdens volunteers can experience during the study period.
After inclusion, study procedures will take maximally 5 hours for each of the
subjects. According to the schedule, subjects will visit the MUMC+ at three
occasions. Subjects will have to take PD01 or placebo supplements once daily
for a period of 6 weeks. Daily they have to note down the time of ingestion in
a log. Subjects will have to follow a documented dietary and health regimen,
and are not allowed to use alcohol or perform strenuous physical exercise
during and 2 days prior to the test days. Study participants will undergo blood
pressure, heart rate and anthropometric measurements. They will have to collect
fecal samples and full urine output for 24 hours. Furthermore, a maximum total
of 258mL blood will be sampled during the study visits by venipuncture. This
may lead to small and transitory hematoma/bruises at the site of the
venipuncture. Furthermore, they have to fill in questionnaires and a 3-day food
record two times during the study period.
Universiteitssingel 40
Maastricht 6229 ER
NL
Universiteitssingel 40
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
Phase 1: healthy individuals (men/women), BMI 18.5-35 kg/m2, age 18-65
Phase 2: Men/women, BMI 25-35 kg/m2, healthy human beings, age between 18 and 71 years, fasting glucose <7.0 mmol/L, Hba1c between 4.4-6.2%
Exclusion criteria
Phase 1:
• History of (severe) cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol.
• Abdominal surgery interfering with gastrointestinal function, upon judgment of the principle investigator
• Abnormal lab test results
• Use of medication
• Use of antioxidants, minerals and vitamin supplements available in pharmacies, drugstores, food markets or in alternative medicine
• Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study
• Use of antibiotics in the 90 days prior to the start of study
• Pregnancy, lactation
• Abuse of products; alcohol (> 20 alcoholic consumptions per week) and drugs
• Smoking
• Blood donation within 3 months before study period
• Weight gain or loss > 3 kg in previous 3 months
• High physical activity (>4.5 hours of running/week)
• History of any side effects towards intake of pro- or prebiotic supplements of any kind
• History of any side effects towards intake of carotenoids
• Prohibited use of pro-, pre- or synbiotics during study period and from one month prior to start of study. A list with forbidden products will be provided (see E4 Lijst_verbodenvoeding_v1)
• Vegetarians/vegans;Phase 2:
• Type 2 diabetes mellitus (defined as fasting plasma glucose >= 7.0 mmol/L);
• History of (severe) cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol.
• Abdominal surgery interfering with gastrointestinal function, upon judgment of the principle investigator)
• Use of medication interfering with endpoints
• Use of antioxidants, minerals and vitamin supplements available in pharmacies, drugstores, food markets or in alternative medicine
• Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study
• Use of antibiotics in the 90 days prior to the start of study
• Known pregnancy, lactation
• Abuse of products; alcohol (> 20 alcoholic consumptions per week) and drugs
• Smoking
• Blood donation within 3 months before study period
• Plans to lose weight or following a hypocaloric diet during the study period;
• Weight gain or loss > 3 kg in previous 3 months
• High physical activity (>4.5 hours of running/week)
• Hormone replacement therapy (women)
• History of any side effects towards intake of pro- or prebiotic supplements of any kind
• History of any side effects towards intake of carotenoids
• Prohibited use of pro-, pre- or synbiotics during study period and from one month prior to start of study. A list with forbidden products will be provided (see E4 Lijst_verbodenvoeding_v1)
• High intake of fruits and vegetables (more than the 75th percentile of dietary intake of fruits and vegetables)
• Vegetarians/vegans
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL50976.068.14 |
| Other | Volgt, registratie in clinicaltrials.gov |