Clinical trial NCT02917863: Randomized Crossover Trial for the Evaluation of the Possible Effects in the Intestine of Two Different Pharmaceutical Forms of L - Thyroxine in Patients With Primary Acquired Hypothyroidism
Official title: Randomized Crossover Trial for the Evaluation of the Possible Effects in the Intestine of Two Different Pharmaceutical Forms of L - Thyroxine in Patients With Primary Acquired Hypothyroidism
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypothyroidism
Keywords: Hypothyroidism
Microbiota
Thyroid hormone
L-Thyroxine
Celiac disease
Lead sponsor: Meyer Children's Hospital IRCCS
Sponsor class: OTHER
First posted: 2016-09-28
Enrollment: 70
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Children with primary acquired hypothyroidism that require Levothyroxine therapy (naïve patients, \< 18 years)
* Informed consent from parents and patient

Exclusion Criteria:

* Age \< 3 years
* Patients with secondary hypothyroidism, euthyroid sick syndrome or thyroid hormone resistant
* Patients with celiac disease, type I diabetes or other known autoimmune diseases
* Patients with genetic diseases or syndromes, such as Down, Williams-Beuren, Turner
* Assumption of antibiotics, probiotics, prebiotics, or other medications that could affect the gut microbiota in the month before the beginning of the study
* Gastrointestinal infectious diseases in the month before the beginning of the study
* Hypersensitivity to levothyroxine or any of the ingredients contained in the two pharmaceutical formulations
* Untreated adrenal insufficiency, untreated pituitary insufficiency and untreated thyrotoxicosis.
* Patients with cardiovascular disease
* Patients who show with impaired pancreatic function measured using the assay in faecal fat (steatocrit) at the screening visit

Primary outcomes:
measure: Effects on gut inflammation parameter (Calprotectin)
timeFrame: 0-6-12 months
measure: Effects on gut absorption parameters
timeFrame: 0-6-12 months
measure: Effects on gut inflammation parameter (Osteoprotegerin)
timeFrame: 0-6-12 months
measure: Effects on gut inflammation parameter (S100-A12 protein)
timeFrame: 0-6-12 months
Secondary outcomes:
measure: Baseline gut microbiota characterization
timeFrame: baseline
measure: Difference in gut microbiota among hypothyroid and healthy subjects
timeFrame: baseline
measure: Incidence of deamidated AGA
timeFrame: 6-12-24 months
measure: Baseline gut inflammation parameters
timeFrame: baseline
measure: Baseline gut absorption parameters
timeFrame: baseline
measure: Difference in Shannon Index in the gut microbiota among liquid and solid L-Thyroxine formulations
timeFrame: 0-6-12 moths
measure: Difference in Chao I in gut microbiota among liquid and solid L-Thyroxine formulations
timeFrame: 0-6-12 moths
measure: Difference in percentage of different species in gut microbiota among liquid and solid L-Thyroxine formulations
timeFrame: 0-6-12 moths
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Meyer Children's Hospital
Study officials:
References:
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