ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02917863
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02917863
Recruitment Status : Recruiting
First Posted : September 28, 2016
Last Update Posted : September 28, 2016
Sponsor:
Information provided by (Responsible Party):
Stefano Stagi, Meyer Children's Hospital

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.

Condition or disease Intervention/treatment Phase
Hypothyroidism Drug: L-Thyroxine (tablet, per os) Drug: L-Thyroxine (oral drops, solution) Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
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 Start Date : May 2016
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothyroidism

Arm Intervention/treatment
Experimental: 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.

Drug: L-Thyroxine (tablet, per os)
Other Name: Eutirox

Active Comparator: 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.

Drug: L-Thyroxine (oral drops, solution)
Other Name: Tirosint




Primary Outcome Measures :
  1. Effects on gut inflammation parameter (Calprotectin) [ Time Frame: 0-6-12 months ]
    Calculate the difference in gut inflammation parameter (calprotectin) among the two groups of patients at T6-T0 and T12-T6

  2. Effects on gut absorption parameters [ Time Frame: 0-6-12 months ]
    Calculate the difference in gut absorption parameters (Steatocrit) among the two groups of patients at T6-T0 and T12-T6

  3. Effects on gut inflammation parameter (Osteoprotegerin) [ Time Frame: 0-6-12 months ]
    Calculate the difference in gut inflammation parameter (osteoprotegerin) among the two groups of patients at T6-T0 and T12-T6

  4. Effects on gut inflammation parameter (S100-A12 protein) [ Time Frame: 0-6-12 months ]
    Calculate the difference in gut inflammation parameter (S100-A12 protein) among the two groups of patients at T6-T0 and T12-T6


Secondary Outcome Measures :
  1. Baseline gut microbiota characterization [ Time Frame: baseline ]
    Qualitative and quantitative (percentage) characterization of gut microbiota before the start of the therapy (T0)

  2. Difference in gut microbiota among hypothyroid and healthy subjects [ Time Frame: baseline ]
    Difference in gut microbiota among hypothyroid patients (T0) and healthy patients (data from Human Microbiome Project)

  3. Incidence of deamidated AGA [ Time Frame: 6-12-24 months ]
    Estimate the incidence of positive patients to deamidated AGA at T6, T12, T24 (follow-up)

  4. Baseline gut inflammation parameters [ Time Frame: baseline ]
    Evaluate gut inflammation (calprotectin, Osteoprotegerin and S100-A12 protein) parameters before the start of the therapy (T0)

  5. Baseline gut absorption parameters [ Time Frame: baseline ]
    Evaluate gut absorption (Steatocrit) parameters before the start of the therapy (T0)

  6. Difference in Shannon Index in the gut microbiota among liquid and solid L-Thyroxine formulations [ Time Frame: 0-6-12 moths ]
    Calculate the difference in Shannon Index (index of diversity) among the two groups of patients at T6-T0 and T12-T6

  7. Difference in Chao I in gut microbiota among liquid and solid L-Thyroxine formulations [ Time Frame: 0-6-12 moths ]
    Calculate the difference in Chao I (Species richness estimator) among the two groups of patients at T6-T0 and T12-T6

  8. Difference in percentage of different species in gut microbiota among liquid and solid L-Thyroxine formulations [ Time Frame: 0-6-12 moths ]
    Calculate the difference in percentage of different species (OTU, operational taxonomic unit) among the two groups of patients at T6-T0 and T12-T6



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02917863


Contacts
Contact: Stefano Stagi, MD +0555662585 stefano.stagi@meyer.it

Locations
Italy
Meyer Children's Hospital Recruiting
Florence, Italy
Contact: Stefano Stagi, MD    +390555662585    stefano.stagi@meyer.it   
Sponsors and Collaborators
Meyer Children's Hospital

Publications:
Responsible Party: Stefano Stagi, MD, Meyer Children's Hospital
ClinicalTrials.gov Identifier: NCT02917863     History of Changes
Other Study ID Numbers: THYR69
2015-001248-12 ( EudraCT Number )
First Posted: September 28, 2016    Key Record Dates
Last Update Posted: September 28, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Stefano Stagi, Meyer Children's Hospital:
Hypothyroidism
Microbiota
Thyroid hormone
L-Thyroxine
Celiac disease

Additional relevant MeSH terms:
Hypothyroidism
Thyroid Diseases
Endocrine System Diseases