ESPEYB17 3. Thyroid Clinical trials for thyroid disease (3 abstracts)
3.12. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial
Groeneweg S , Peeters RP , Moran C , Stoupa A , Auriol F , Tonduti D , Dica A , Paone L , Rozenkova K , Malikova J , van der Walt A , de Coo IFM , McGowan A , Lyons G , Aarsen FK , Barca D , van Beynum IM , van der Knoop MM , Jansen J , Manshande M , Lunsing RJ , Nowak S , den Uil CA , Zillikens MC , Visser FE , Vrijmoeth P , de Wit MCY , Wolf NI , Zandstra A , Ambegaonkar G , Singh Y , de Rijke YB , Medici M , Bertini ES , Depoorter S , Lebl J , Cappa M , De Meirleir L , Krude H , Craiu D , Zibordi F , Oliver Petit I , Polak M , Chatterjee K , Visser TJ & Visser WE
To read the full abstract: Lancet Diabetes Endocrinol. 2019;7:695–706.
The hallmarks of MCT8 deficiency are severe psychomotor retardation due to intracellular hypothyroidism in neuronal tissues and peripheral T3 thyrotoxicosis associated low weight, muscle wasting, high normal or increased heart rate and systolic blood pressure. TRIAC – the T3 analogue 3,3’,5-tri-iodothyroacetic acid – enters target cells in an MCT8 independent way, and therefore could potentially improve intracellular thyroid hormone deficiency in the brain. On the other hand, TRIAC has only weak thyromimetic activity in peripheral tissues, thus represents a bona fide candidate to improve the MCT8 deficiency associated imbalance between neuronal intracellular hypothyroidism and peripheral hyperthyroidism.
This single-arm, phase 2 clinical trial in 45 pediatric and adult patients with MCT8 deficiency revealed beneficial biochemical and clinical effects of TRIAC treatment during 12 months on peripheral T3 thyrotoxicosis: T3 levels, cardiovascular parameters, and bodyweight improved and these effects were maintained in 10 patients who continued on a treatment extension for a median of 40 months. A clear improvement in gross motor function was seen in 6 of 7 patients treated before age 4 years, but there was no change in patients aged 4 years and older.
These data are important and provide evidence of effectiveness and safety of TRIAC for alleviating peripheral hyperthyroidism in MCT8 deficient patients. Neurologic improvement was observed only in the youngest patients, advocating starting TRIAC treatment as early as possible. A next clinical trial is under way to investigate TRIAC effectiveness when started in childhood (Triac Trial II; ClinicalTrials.gov number NCT02396459).
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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