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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001248-12 | EudraCT Number |
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Thyroid disorders, in particular hypothyroidism, are associated with gastrointestinal impairment, such as celiac disease. A study reported an increased prevalence of celiac disease in a large cohort of children affected by congenital hypothyroidism, underlying the relationship between these two conditions. The hypothesis of our study is that the onset of celiac disorder may be related to the gut concentration of thyroid hormone (TH) in hypothyroidism patients treated with replacement therapy. In fact, TH replacement therapy showed a low bioavailability with a consequent high gut concentration. Two different pharmaceutical formulations (liquid and solid, per os) are available. The liquid one has a better absorption profile and bioavailability than the solid; therefore, it is associated with a low TH intestinal concentration. According to our hypothesis, the solid TH formulation could increase the microbial diversity in the gut instead of the liquid form, due to the high local TH concentration. Based on these findings, the purpose of this study is to evaluate the effect of two different pharmaceutical formulations of TH on the gut in terms of modification of gut microbiota, inflammatory parameters and gut absorption.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Solid L-Thyroxine | Experimental | Patients assume L-Thyroxine (tablet, per os) according to the Summary Product Characteristics for 6 months (then switch to the other formulation). Dosage in children with hypothyroidism: 0-6 months: 10 mcg/kg body weight/die 6-12 months: 8 mcg/kg body weight/die 1- 5 years: 6 mcg/kg body weight/die 5-10 years: 4 mcg/kg body weight/die Dosage in adults: initial dose of 50mcg/die; maintenance dose 100-200 (300) mcg/die (medium dose 2-2,5 mcg/kg body weight/die). Dosage will be adjusted according to TSH level. |
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| Liquid L-Thyroxine | Active Comparator | Patients assume L-Thyroxine (oral drops, solution) according to the Summary Product Characteristics for 6 months (then switch to the other formulation). Dosage in children with acquired hypothyroidism: initial dose: 12,5-50 mcg/die maintenance dose: 100-150 mcg/m2 body surface area Dosage in adults: initial dose: 50 mcg/die; maintenance dose: 100-200 (300) mcg/die (medium dose 2-2,5 mcg/kg body weight/die). Dosage will be adjusted according to TSH level. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Thyroxine (tablet, per os) | Drug |
|
| |
| L-Thyroxine (oral drops, solution) |
| Measure | Description | Time Frame |
|---|---|---|
| Effects on gut inflammation parameter (Calprotectin) | Calculate the difference in gut inflammation parameter (calprotectin) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 months |
| Effects on gut absorption parameters | Calculate the difference in gut absorption parameters (Steatocrit) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 months |
| Effects on gut inflammation parameter (Osteoprotegerin) | Calculate the difference in gut inflammation parameter (osteoprotegerin) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 months |
| Effects on gut inflammation parameter (S100-A12 protein) | Calculate the difference in gut inflammation parameter (S100-A12 protein) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline gut microbiota characterization | Qualitative and quantitative (percentage) characterization of gut microbiota before the start of the therapy (T0) | baseline |
| Difference in gut microbiota among hypothyroid and healthy subjects |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stefano Stagi, MD | Contact | +0555662585 | stefano.stagi@meyer.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Meyer Children's Hospital | Recruiting | Florence | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21757873 | Background | Stagi S, Manoni C, Cecchi C, Chiarelli F, de Martino M. Increased risk of coeliac disease in patients with congenital hypothyroidism. Horm Res Paediatr. 2011;76(3):186-92. doi: 10.1159/000328723. Epub 2011 Jul 15. | |
| 1237554 | Background | Smith DW, Klein AM, Henderson JR, Myrianthopoulos NC. Congenital hypothyroidism--signs and symptoms in the newborn period. J Pediatr. 1975 Dec;87(6 Pt 1):958-62. doi: 10.1016/s0022-3476(75)80918-8. |
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| Drug |
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Difference in gut microbiota among hypothyroid patients (T0) and healthy patients (data from Human Microbiome Project)
| baseline |
| Incidence of deamidated AGA | Estimate the incidence of positive patients to deamidated AGA at T6, T12, T24 (follow-up) | 6-12-24 months |
| Baseline gut inflammation parameters | Evaluate gut inflammation (calprotectin, Osteoprotegerin and S100-A12 protein) parameters before the start of the therapy (T0) | baseline |
| Baseline gut absorption parameters | Evaluate gut absorption (Steatocrit) parameters before the start of the therapy (T0) | baseline |
| Difference in Shannon Index in the gut microbiota among liquid and solid L-Thyroxine formulations | Calculate the difference in Shannon Index (index of diversity) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 moths |
| Difference in Chao I in gut microbiota among liquid and solid L-Thyroxine formulations | Calculate the difference in Chao I (Species richness estimator) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 moths |
| Difference in percentage of different species in gut microbiota among liquid and solid L-Thyroxine formulations | Calculate the difference in percentage of different species (OTU, operational taxonomic unit) among the two groups of patients at T6-T0 and T12-T6 | 0-6-12 moths |
| 25203248 | Background | Robertson HM, Narayanaswamy AK, Pereira O, Copland SA, Herriot R, McKinlay AW, Bevan JS, Abraham P. Factors contributing to high levothyroxine doses in primary hypothyroidism: an interventional audit of a large community database. Thyroid. 2014 Dec;24(12):1765-71. doi: 10.1089/thy.2013.0661. |
| 23835180 | Background | Sanchez E, Donat E, Ribes-Koninckx C, Fernandez-Murga ML, Sanz Y. Duodenal-mucosal bacteria associated with celiac disease in children. Appl Environ Microbiol. 2013 Sep;79(18):5472-9. doi: 10.1128/AEM.00869-13. Epub 2013 Jul 8. |
| 24610609 | Background | Ianiro G, Mangiola F, Di Rienzo TA, Bibbo S, Franceschi F, Greco AV, Gasbarrini A. Levothyroxine absorption in health and disease, and new therapeutic perspectives. Eur Rev Med Pharmacol Sci. 2014;18(4):451-6. |
| 9364356 | Background | Chao T, Wang JR, Hwang B. Congenital hypothyroidism and concomitant anomalies. J Pediatr Endocrinol Metab. 1997 Mar-Apr;10(2):217-21. doi: 10.1515/jpem.1997.10.2.217. |
| 12583961 | Background | Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003 Feb 8;361(9356):512-9. doi: 10.1016/S0140-6736(03)12489-0. |
| ID | Term |
|---|---|
| D007037 | Hypothyroidism |
| D002446 | Celiac Disease |
| ID | Term |
|---|---|
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D013974 | Thyroxine |
| D013607 | Tablets |
| D012996 | Solutions |
| ID | Term |
|---|---|
| D013963 | Thyroid Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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