to investigate whether microbial transplantation from either allogenic (healthy) or autologous (own) donor, administered through a small intestinal tube, has beneficial effects on immune status, betacell function c-peptide secretion upon mixed meal…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
the primary endpoint is betacell insulin secretion capacity: (beta cell
function as assessed by mixed meal test) at 0,2,6,9 and 12 months.
Secondary outcome
Secundary endpoint is changes in Immunologic parameters : FACS on periferal
leukocyte subsets (change cytokine/Tr1/nTreg/Th2/Th17 subset population),
cellular islet autoimmunity (CD4 and CD8) in relation to mucosa innate en
adaptive immunity (CCR4, CXCR3,CXCL10) and antiGAD /c-peptide plasma
concentrations at 0,2,4,6,9 en 12 months. Our tertiary endpoint is changes in
small intestinal (at baseline and after 6 months) and fecal gutmicrobiota
composition at 0,2, 6, 9 and 12 months. Moreover, our fourth endpoint pertains
changes in plasma biochemistry (HbA1c levels) and urine (microalbuminuria) at
0, 2, 6, 9 and 12 months. Finally, our fifth endpoint is intestinal integrity:
Changes in small intestinal genes (ILLUMINA array en occluding expression) at
baseline and at 6 months.
Background summary
Type 1 diabetes mellitus is an autoimmune disease (associated with progressive
betacell destruction and subsequent insulin dependence in the first 2-3 decades
of life), which associated with an increased morbidity and mortality risk
compared to healthy subjects . In this regard, altered intestinal microbiota
composition has been implicated to play an important role in (human) metabolism
as well as autoimmune diseases (eg inflammatory bowel diseases like Crohn and
Ulcerative Colitis). In this regard, recent mouse and human studies have
suggested that bacteria from the small intestine could trigger *-cell
destruction, most likely by inducing an altered T-helper cell type 17 (Th17)
population in the small-intestinal lamina propria. We thus hypothesize that
reshaping the (small) intestinal microbiota could stabilize the betacell
destruction of the pancreas, thus (partly) preventing exogenous insulin
dependence.
Study objective
to investigate whether microbial transplantation from either allogenic
(healthy) or autologous (own) donor, administered through a small intestinal
tube, has beneficial effects on immune status, betacell function c-peptide
secretion upon mixed meal test or MMT) in recently diagnosed type 1 diabetes
mellitus. A parallel objective is to see which small (intestinal biopsies) and
large intestinal (fecal samples) microbiota are associated with these clinical
changes.
Study design
randomized double blind controlled trial
Intervention
after bowel lavage with macrogol, patients will be treated by small intestinal
infusion via a duodenal tube of a microbial solution derived from an allogenic
(healthy donor n=17) or autologous (own) fecal sample (n=17) every
8 weeks during 6 months (0, 8, 16 wks).
Study burden and risks
DM1 subjects are five times submitted to mixed meal test (MMT) and two times to
agastroduodenoscopy, for which no side-effects are expected. Because strict
conditions are applied to healthy fecal donors, the risk of spreaking potential
pathogens seems nil. We thus think that the knowlegde of this trial on the
pathophysiology of Type 1 diabetes mellitus related progressive betacell
destruction and subsequent insulin dependence induced by "bad" commensal
bacteria outweights the minor potential risks. Moreover, this study could
provide us with novel treatment leads (probiotics) aimed at conserving
betacel/pancreas function in DM1 patients.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
newly diagnosed (< 6 weeks) patients with type 1 diabetes (n<=34, aged 18-39 years, BMI 20-25 kg/m2, male/females, no concomitant medication use except insulin, plasma C-peptide > 0.2 mmol/l and/or >1.2 ng/mL after MMT), fasting glucose 10-13 mmol/l and positive anti-GAD and/or anti-IA-2 titer concentrations.
Exclusion criteria
Use of concomitant medication including PPI and antibiotics past three months, smoking, (expected) prolonged compromised immunity (due to recent cytotoxic chemotherapy or HIV infection with a CD4 count < 240).
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 | NL42147.018.12 |