NCT05682482: T3-4-Hypo

A National Randomized Placebo-controlled Double-blind Multicenter Trial of LT4/LT3 Combination Therapy in Patients with Autoimmune Hypothyroidism: the T3-4-Hypo Trial.

Recruiting now Phase 3 Last updated 25 February 2025

What this trial tests

Phase 3 trial testing LT3 (liothyronine) in Autoimmune Hypothyroidism in 600 participants. Currently enrolling.

Timeline

7 October 2022

Primary endpoint
1 January 2028

1 January 2028

Quick facts

Lead sponsor	M. Medici
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	600
Start date	7 October 2022
Primary completion	1 January 2028
Estimated completion	1 January 2028
Sites	19 locations across Netherlands

Drugs / interventions tested

• LT3 (liothyronine) — full drug profile →
• Placebo

Conditions studied

• Autoimmune Hypothyroidism — all drugs for Autoimmune Hypothyroidism →

Sponsor

M. Medici — full company profile →

Who can join

18 and older, any sex, with Autoimmune Hypothyroidism. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Mean change from baseline to 52 weeks in the ThyPRO tiredness subscale scores.
  Time frame: 52 weeks
  Thyroid specific Patient Reported Outcome (ThyPRO) questionnaire, with the tiredness subscale ranging from 0-100 (higher scores indicate a worse outcome). ThyPRO Questionnaires will be performed at every RCT visit.
• Effect sizes in genetic subgroups
  Time frame: 52 weeks
  In case it is confirmed that LT4/LT3 combination therapy reduces tiredness compared to LT4 treatment alone, we will simultaneously investigate whether effect sizes are higher in patients with genetic variation in the type 2 deiodinase (DIO2-rs225014) and effect sizes are higher in patients with genetic variation in the monocarboxylate transporter 10 (MCT10-rs17606253), ensuring control of the stud

Sponsor's own description

Hypothyroidism is common, affecting 5% of the general population, for which levothyroxine (LT4) monotherapy is the standard treatment. Despite normalized serum thyroid hormone levels, 10-15% of LT4 treated patients have various persistent complaints, the most important of which is tiredness. This could be explained by the fact that physiological T4/T3 ratios cannot be reached with LT4 monotherapy, as in a healthy individual T3 is not only derived from T4/T3 conversion but is also directly produced by the thyroid itself. Studies have reported contradicting results as to whether addition of liothyronine (LT4/LT3 combination therapy) in patients with persistent tiredness on LT4 monotherapy is effective or not. Studies have suggested higher effectiveness in patients carrying genetic variation in the type 2 deiodinase (DIO2-rs225014) and monocarboxylate transporter 10 (MCT10-rs17606253) genes.

Objective: To investigate whether addition of liothyronine (LT4/LT3 combination therapy) in in patients with persistent tiredness on LT4 monotherapy is effective or not in relieving tiredness.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism.
   Phan GQ, Yavuz S, Stamatouli AM, Madan R, et al · · 2025 · cited 2× · PMID 40130156 · DOI 10.3389/fendo.2025.1522753
2. Medical Applications of Molecular Biotechnologies in the Context of Hashimoto's Thyroiditis.
   Trovato M, Valenti A. · · 2023 · cited 1× · PMID 37371008 · DOI 10.3390/diagnostics13122114