No registrations found.
ID
Source
Brief title
Health condition
type 1 diabetes mellitus
Sponsors and support
Intervention
Outcome measures
Primary outcome
Preservation of residual betacell insulin secretion capacity/beta cell function as assessed by mixed meal test (MMT) at 0, 6 and 12 months.
Secondary outcome
1. Immunologic parameters: Changes in immunology based on FACS of periferal leukocyte subsets (changes in Tr1/nTreg/Th2/ Th17/NKT/TCRγδ subsets, islet autoimmunity (CD4 and CD8) ) in relation to mucosa innate en adaptive immunity (CCR4, CXCR3,CXCL10) as well as plasma markers of autoimmunity ( antiGAD/IA2/c-peptide plasma concentrations) at 0, 2, 6, 9 and 12 months;
2. Intestinal microbiota: Changes in small intestinal (at baseline and 6 months) and fecal gut microbiota composition at 0, 2, 6, 9 and 12 months;
3. Glycemic control: Changes in plasma biochemistry (HbA1c),urine (microalbuminuria)
and subsequent exogenous insulin dose use at 0, 2, 6, 9 and 12 months;
4. Intestinal epithelial integrity: Changes in small intestinal epithelial genes (ILLUMINA array) at baseline and 6 months.
Background summary
We propose to test the effect of multiple infusions of one healthy donor (=allogenic) compared to multipele infusion of own feces (=autologous) on residual betacell function, immunologic status (in periferal blood and mucosa) and gut microbiota composition both in small intestinal (biopsies) and fecal samples. Using this protocol we might be able to disentangle potential causality of intestinal bacteria in the pathophysiology of type 1 diabetes mellitus.
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 (Cpeptide secretion upon a mixed meal test (MMT) in recently diagnosed type 1 diabetes mellitus. Moreover, we aim to see which small (intestinal biopsies) and large intestinal (fecal samples) microbiota are associated with these clinical changes.
Study design
At baseline, 2, 6, 9 and 12 months.
Intervention
We will compare the effect of multiple allogenic (using feces of thorouhgly screened healthy donor) versus autologous (=using own feces) fecal transplantation on preservation of beta cell insulin secretion capacity and normalisation of immunological tone (Thelper cell subsets in blood) in subjects recently diagnosed with type 1 diabetes mellitus. Fecal transplantation (using fresh morning fecal sample) will be performed by introduction of a duodenal tube (either by gastroduodenoscopy or by Cortrak device assisted electromagnetic positioning) , followed by total bowel-lavage with cetomacrogol and subsequent of infusion of processed fecal sample. beta cell insulin secretion capacity will be tested by mixed meal test and immunological tone (Thelper cell subsets in blood) by FACS analysis.
MEIBERGDREEF 9, KAMER F4.159.2
M. Nieuwdorp
Amsterdam 1105 AZ
The Netherlands
+31 (0)20 5666612
m.nieuwdorp@amc.uva.nl
MEIBERGDREEF 9, KAMER F4.159.2
M. Nieuwdorp
Amsterdam 1105 AZ
The Netherlands
+31 (0)20 5666612
m.nieuwdorp@amc.uva.nl
Inclusion criteria
Newly diagnosed (< 6 weeks) patients with type 1 diabetes (n=34, aged 18-30 years, BMI 18-25 kg/m2, with still residual betacell function (as indicated by plasma C-peptide > 0.2 mmol/l and/or >1.2 ng/mL after MMT), male/females, will be recruited by poster advertisement.
Exclusion criteria
Subjects with diagnosis or symptoms of another autoimmune disease (eg hypo- or hyperthyroidism, coeliakie, rheumatoid arthritis or inflammatory bowel disease like Crohn/Colitis Ulcerosa) are not able to participate. Smoking, (expected) prolonged compromised immunity (due to recent cytotoxic chemotherapy or HIV infection with a CD4 count < 240) as well as antibiotics use in the last 3 months and PPI use is seen as an exclusion criterium.
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 |
|---|---|
| NTR-new | NL3542 |
| NTR-old | NTR3697 |
| Other | METC AMC : 201/295 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |