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 IRCCS

Status and phase: Unknown; Phase 4

Conditions: Hypothyroidism

Treatments: Drug: L-Thyroxine (oral drops, solution); Drug: L-Thyroxine (tablet, per os)

Study type: Interventional

Funder types: Other

Identifiers

NCT02917863

THYR69

2015-001248-12 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 70 estimated patients

Sex: All

Ages: 3 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

70 participants in 2 patient groups

Solid L-Thyroxine

Experimental group

Description:

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.

Treatment:

Drug: L-Thyroxine (tablet, per os)

Liquid L-Thyroxine

Active Comparator group

Description:

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.

Treatment:

Drug: L-Thyroxine (oral drops, solution)