Primary Objective: - to establish if a gut microbiome perturbation affects APS disease phenotype.Secondary Objective(s): - to identify biomarkers that are responsive gut microbiome perturbation.- to establish if gut microbiome perturbation affects…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Autoimmune disorders
- Abortions and stillbirth
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study outcome is the composite of a broad panel of APS
pathophysiology-related blood biomarkers. These biomarkers are regarded to
collectively reflect the APS phenotype.
Secondary outcome
The secondary outcome is gut permeability as measured by lactulose/mannitol
test.
Background summary
Antiphospholipid syndrome (APS) is a common autoimmune disease. Thrombosis,
recurrent miscarriage, pre-eclampsia, placental insufficiency, fetal death and
the often fatal catastrophic antiphospholipid syndrome, are all manifestations
of APS. The origin of the autoantibodies that characterize the syndrome is
unknown. The gut microbiome, the ecosystem of microbes residing in the
intestinal tract, is contributes to autoimmunity, and recent animal studies
suggest an etiological role of the microbiome in APS. We aim to establish
proof-of-concept for an etiological role of the gut microbiome in human APS.
Study objective
Primary Objective:
- to establish if a gut microbiome perturbation affects APS disease phenotype.
Secondary Objective(s):
- to identify biomarkers that are responsive gut microbiome perturbation.
- to establish if gut microbiome perturbation affects intestinal permeability
in APS patients.
Study design
The study will have a pretest posttest design in which all subjects undergo a
short course of antibiotic treatment between measurement time points. During
the study all patients will undergo a 7 day treatment course of oral
vancomycin, 500mg 4 times daily, a standard antibiotic.
Study burden and risks
There are four site visits. The first visit will last 1 hour, the other visits
will last 4 hours each. No serious side effects are suspected of vancomycin as
it is administered orally and is very poorly absorbed from the gut. Side
effects of oral administration include temporary abdominal discomfort,
bloating, flatulence and nausea. Subject will drink a single dose of mannitol
and lactulose at each visit which might cause mild temporary bloating and
flatulence. Subjects will have to be sober for approximately 10 hours overnight
for these tests. 60 ml of blood will be drawn on three occasions.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet the
revised Sapporo classification criteria for antiphospholipid syndrome:
At least one of the clinical and at least one of the laboratory criteria below
Clinical criteria
1. Thrombosis
One or more clinical episodes of arterial, venous, or small vessel thrombosis,
in any tissue or organ. Thrombosis must be confirmed by objective validated
criteria (i.e., unequivocal findings of appropriate imaging studies or
histopathology).
2. Pregnancy morbidity
(a) One or more unexplained deaths of a morphologically normal fetus at or
beyond the 10th week of gestation, with normal fetal morphology documented by
ultrasound or by direct examination of the fetus, or
(b) One or more premature births of a morphologically normal neonate before the
34th week of gestation because of: (i) eclampsia or severe pre-eclampsia de*ned
according to standard de*nitions, or (ii) recognized features of placental
insu*ciency*,or
(c) Three or more unexplained consecutive spontaneous abortions before the 10th
week of gestation, with maternal anatomic or hormonal abnormalities and
paternal and maternal chromosomal causes excluded.
Laboratory criteria
a Lupus anticoagulant (LA) present in plasma, on two or more occasions at least
12 weeks apart, detected according to the guidelines of the International
Society on Thrombosis and Haemostasis (Scienti*c Subcommittee on
LAs/phospholipid-dependent antibodies).
b. Anticardiolipin (aCL) antibody of IgG and/or IgM isotype in serum or plasma,
present in medium or high titer (i.e. >40 GPL or MPL, or >the 99th percentile),
on two or more occasions, at least 12 weeks apart, measured by a standardized
ELISA.
c. Anti-b2glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma
(in titer >the 99th percentile), present on two or more occasions, at least 12
weeks apart, measured by a standardized ELISA, according to recommended
procedures.
Exclusion criteria
- Age below 18 years
- Current use of antibiotics
- History of gastro-enteritis in the past month
- History of inflammatory bowel disease
- Current use of a vitamine K antagonist
- Planned change in the following medication during the study period (either
start, stop or dose change): platelet aggregation inhibitors, oral
anticoagulants, heparins, hormonal therapy.
- Current pregnancy or pregnancy in the past 6 weeks
- Arterial or venous thrombosis in the past month
- Allergy to vancomycin
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 | NL67782.018.18 |