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

NCT ID: NCT02917863

Last Updated: 2016-09-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2019-05-31

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.

Conditions

Hypothyroidism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Solid L-Thyroxine

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.

Group Type: EXPERIMENTAL

L-Thyroxine (tablet, per os)

Intervention Type: DRUG

Liquid L-Thyroxine

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.

Group Type: ACTIVE_COMPARATOR

L-Thyroxine (oral drops, solution)

Intervention Type: DRUG

Interventions

L-Thyroxine (tablet, per os)

Intervention Type: DRUG

L-Thyroxine (oral drops, solution)

Intervention Type: DRUG

Other Intervention Names

Eutirox; Tirosint

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Meyer Children's Hospital IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Stefano Stagi

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Meyer Children's Hospital

Florence, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Stefano Stagi, MD

Role: CONTACT

stefano.stagi@meyer.it

+0555662585

Facility Contacts

Stefano Stagi, MD

Role: primary

stefano.stagi@meyer.it

+390555662585

References

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.

Reference Type: BACKGROUND

PMID: 21757873 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1237554 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25203248 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23835180 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24610609 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9364356 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12583961 (View on PubMed)

Other Identifiers

2015-001248-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

THYR69

Identifier Type: -

Identifier Source: org_study_id