Clinical Trial: 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 Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Hy

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.

Detailed Summary:
Sponsor: Meyer Children's Hospital

Current Primary Outcome:

  • 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
  • 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
  • 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
  • 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Baseline gut microbiota characterization [ Time Frame: baseline ]
    Qualitative and quantitative (percentage) characterization of gut microbiota before the start of the therapy (T0)
  • 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)
  • 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)
  • Baseline gut inflammation parameters [ Time Frame: baseline ]
    Evaluate gut inflammation (calprotectin, Osteoprotegerin and S100-A12 protein) parameters before the start of the therapy (T0)
  • Baseline gut absorption parameters [ Time Frame: baseline ]
    Evaluate gut absorption (Steatocrit) parameters before the start of the therapy (T0)
  • 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
  • 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
  • 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


Original Secondary Outcome: Same as current

Information By: Meyer Children's Hospital

Dates:
Date Received: September 7, 2016
Date Started: May 2016
Date Completion: May 2019
Last Updated: September 26, 2016
Last Verified: September 2016