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

Meyer Children's Hospital IRCCS70 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

Conditions

Hypothyroidism

Interventions

Eligibility

Sex: ALLMin age: 3 YearsMax age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 0-6-12 months

Secondary Outcomes

Baseline gut microbiota characterization

Qualitative and quantitative (percentage) characterization of gut microbiota before the start of the therapy (T0)

Time frame: baseline

Difference in gut microbiota among hypothyroid and healthy subjects

Difference in gut microbiota among hypothyroid patients (T0) and healthy patients (data from Human Microbiome Project)

Time frame: baseline

Incidence of deamidated AGA

Estimate the incidence of positive patients to deamidated AGA at T6, T12, T24 (follow-up)

Time frame: 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)

Time frame: baseline

Baseline gut absorption parameters

Evaluate gut absorption (Steatocrit) parameters before the start of the therapy (T0)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 0-6-12 moths

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts