To investigate whether microbial transplantation from either allogenic (healthy) or autologous (own) donor, administered every 8 weeks during 6 months through a small intestinal tube, has beneficial effects on residual thyroid function at baseline,…
ID
Source
Brief title
Condition
- Thyroid gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is effect on residual thyroid function as determined by
plasma thyroid markers (TSH/FT4 and antiTPO) as well as determined by rTSH test
(0.9mg intramuscular injection) at baseline, 6, 12 and 24 months.
Secondary outcome
Secondary endpoints are reduction in autoimmunity makers including FACS on
peripheral blood lymfocyte subsets (change Th17 (CD4+IL-17+) and T-regs
(CD4+CD25+ FoxP3+) and in FNAC thyroid (for Imaging Mass Spectrometry) at
baseline and after 6 and 24 months. Moreover, intestinal transit time (Sitzmark
capsules) will be determined at these three timepoints. Also, quality of life
questionnaires ( ThyPro, a disease specific QoL scale) and dietary intake lists
online (via mijn.voedingscentrum.nl/nl/eetmeter) are measured at 0, 6, 12 and
24 months. Finally, oral and fecal intestinal microbiota and plasma metabolite
are determined at 0, 6, 12 and 24 months.
Background summary
Autoimmune hypothyroidism is a frequently seen disease (400.000 patients in the
Netherlands) which is associated with dysfunction of thyroid hormone
production, for which the aetiologie is not well known. Treatment comprises of
supplementation of thyroid hormone, a treatment that is not affecting the
underlying autoimmune process. Autoimmune hypothyroidism is associated with
increase morbidity (increased fatigue, lower quality of life). Recent data have
shown that Autoimmune hypothyroidism is associated with altered gutmicrobiota
composition. Since we have shown over the last 10 years at AMC in about 500
patients that donor fecal transplantation is safe and has effects on human
metabolism, we therefore aim to study the effect of allogenic versus autologous
fecal transplantation in subjects with subclinical autoimmune hypothyroidism.
Study objective
To investigate whether microbial transplantation from either allogenic
(healthy) or autologous (own) donor, administered every 8 weeks during 6 months
through a small intestinal tube, has beneficial effects on residual thyroid
function at baseline, 6 , 12 and 24 months after intervention in recently
diagnosed patients (n=34) with subclinical autoimmune hypothyroidism.
Study design
Double blind randomized controlled single center trial.
Intervention
fecal transplantation from either allogenic healthy donors or own (autologous)
will be given three times (baseline, 8 and 16 weeks) via a small intestinal
tube
Study burden and risks
At this moment, there is no treatment available that stops autoimmune
destruction of the thyroid gland that results in hypothyreoïdie. Based on the
fact the this is a frequently seen disease (400.000 patients in the
Netherlands) associated with high morbidity (reduced quality of life and
chronic fatigue) new treatment modalities are warranted. Since recent data has
shown that these patients have altered gutmicrobiota and bowel function in
conjunction with fact that we have shown at AMC that fecal transplantation with
donor or own feces is safe and has no side effects in more than 500 patients,
we feel that this treatment should be tested in this patient group. In total
patients visit AMC for 40 hours during 2 years and In total 240 ml blood is
drawn. Also three FNACs of thyroid gland and intestinal transit time tests as
well as four Thyrogen thyroid function tests are done. As treatment with
intramuscular injection of rTSH (Thyrogen) as well as ultrasound guided FNAC
(fine needle aspiration) to obtain thyroid tissue is regularly done in routine
patient care, we feel that the potential risks of this study do outweigh the
potential benefit ( new bacterial strains and/or metabolites that can stop
autoimmune destruction and thyroid dysfunction).
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Newly diagnosed patients with subclinical autoimmune hypothyroidism aged 18-70 years,
TSH > 10 mU/L
BMI 18-30 kg/m2,
male/females,
no concomitant medication,
antiTPO positive and increased TSH (above 5.0mE/L) with FT4 within normal reference value ;feces donoren:
Healthy male/female volunteers
aged 18-70 years,
BMI 18-28 kg/m2,
no medication use,
no family history of autoimmune diseases
Exclusion criteria
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).;fecal donors:
1. (chronic) diarrhoea
2. family history of autoimmune diseases (type 1 diabetes, Hashimoto hypothyreoidism, Graves hyperthyreoidism, rheumatoid arthritis, inflammatory bowel diseases eg. Crohn*s disease, Colitus ulcerosa or coeliakie)
3. HIV, HAV, HBV, HCV, active CMV, active EBV
4. Unsafe sex practice (questionnaire)
5. presence of fecal bacterial pathogens (salmonella, Shigella, Campylobacter, Yersinia) or parasites
6. positive C. difficile stool test
7. any medication use including PPI and antibiotics
8. smoking
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL69382.018.19 |
| OMON | NL-OMON23348 |