LT4/LT3 Combination Therapy Versus LT4 Monotherapy in Patients with Autoimmune Hypothyroidism.
Key facts
- Where
- Almere Stad, Amsterdam, Apeldoorn, Arnhem, Breda, Dirksland, Dordrecht, Emmen, Goes, Groningen, Hardenberg, Nijmegen, Rotterdam, Schiedam, Sittard, Utrecht, Veldhoven, and Venlo, NetherlandsSee the 19 sites
- Phase
- Phase 3
Where in Netherlands
- FlevoziekenhuisAlmere Stad, NetherlandsContact: Antoon Van Lierop, MD PhDTaking people
- Amsterdam UMC, location AMCAmsterdam, NetherlandsContact: Eveline Bruinstroop, MD PhDTaking people
- Gelre ZiekenhuizenApeldoorn, NetherlandsContact: Marlies Bosselaar, MD PhDNot yet recruiting
- RijnstateArnhem, NetherlandsContact: Sean Roerink, MD PhDTaking people
- Amphia ZiekenhuisBreda, NetherlandsContact: Charlotte Krol, MD PhDTaking people
- Van Weel-Bethesda HospitalDirksland, NetherlandsContact: Ellen v Schaik, MDTaking people
- Albert Schweitzer HospitalDordrecht, NetherlandsContact: Rosalie Kiewiet-Kemper, MD PhDTaking people
- TreantEmmen, NetherlandsContact: Eveline van Dam, MD PhDNot yet recruiting
- Admiraal de Ruyter HospitalGoes, NetherlandsContact: Kees vd Berge, MD PhDTaking people
- University Medical Center GroningenGroningen, NetherlandsContact: Wouter Zandee, MD PhDTaking people
- Saxenburgh MCHardenberg, NetherlandsContact: Simone Spoorenberg, MD PhDTaking people
- RadboudumcNijmegen, NetherlandsContact: Romana Netea-Maier, Prof. dr.Taking people
- Erasmus Medical CenterRotterdam, NetherlandsContact: Marco Medici, MD PhDTaking people
- Maasstad HospitalRotterdam, NetherlandsContact: Charlotte v Noord, MD PhDTaking people
- Franciscus Gasthuis & VlietlandSchiedam, NetherlandsContact: Marlies Kevenaar, MD PhDTaking people
- ZuyderlandSittard, NetherlandsContact: Roderick Tummers-de Lind van Wijngaarden, MD PhDTaking people
- University Medical Center UtrechtUtrecht, NetherlandsContact: Stephanie vd Leij, MDTaking people
- Maxima Medical CenterVeldhoven, NetherlandsContact: Pleun Wouters-van Poppel, MD PhDTaking people
- Vie Curie MCVenlo, NetherlandsContact: Joop van den Bergh, Prof. dr.Not yet recruiting
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorTrial details
- Who runs it
- M. Medici
- Trial code
- NCT05682482
- Record updated
- 26 February 2025
- Original 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.Read full original descriptionShow less
A National Randomized Placebo-controlled Double-blind Multicenter Trial of LT4/LT3 Combination Therapy in Patients with Autoimmune Hypothyroidism: the T3-4-Hypo Trial.
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.
Inclusion: Patients with overt or subclinical primary hypothyroidism 18 years or older.*; LT4 monotherapy for at least 6 months; LT4 monotherapy dose of 75-225 microg, with at least a dose of 1.2 microg/kg; TSH levels within the assay-specific reference ranges for at least 3 months; Severe tiredness with a large negative impact on daily life for at least 6 months, with or without other persisting complaints. This is based on the patient's own experience, without judgment of the treating physician; Sufficiently fluent in Dutch and able to read Dutch; Thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibody positivity is not a requirement as these have frequently not been determined. Instead, we ensure that we only include patients with autoimmune hypothyroidism by excluding other causes of hypothyroidism (see exclusion criteria).
Exclusion: Thyroid surgery, radioactive iodine treatment, or head and/or neck radiotherapy; Use of thyroid interfering drugs (current/past use of amiodarone, immunotherapy, tyrosin kinase inhibitors, interferon, or lithium and current use of oral or iv corticosteroids or dopamine); Current psychiatric disease treated at a "gespecialiseerde GGZ instelling"**; Clinical diagnosis of dementia; Clinically relevant functional or structural abnormal heart (e.g., cardiomyopathy or valve disease); Recent acute coronary syndrome or unstable angina pectoris (<4 weeks); Other obvious medical explanation for tiredness (e.g. end-stage renal disease, anemia, COPD stage IV, cancer, etc.); Other obvious major life event explanation for tiredness (e.g., mourning, loss of job); Postpartum thyroiditis is not an exclusion criterium; Treatments of mild non-complex psychological/psychiatric complaints are done in the " basis GGZ", e.g. consisting of conversations with a psychologist or psychotherapist, or via internet (e-health). "Gespecialiseerde GGZ" encompasses treatments of more severe psychological/psychiatric complaints. (link: Basis GGZ en gespecialiseerde GGZ | Geestelijke gezondheidszorg (GGZ) | Rijksoverheid.nl); Current conduction disorder on ECG (i.e, QRS>120 ms or prolonged QTc (women≥460 ms and men≥450 ms)); Women of reproductive age not using adequate contraception, who are not sterilized and do not have a sterilized partner. Adequate contraceptives include the contraceptive pill, patch, injection, implant, intrauterine device or system, vaginal ring, diaphragm or cap, and condom; Congenital hypothyroidism, hypothyroidism after (sub)acute thyroiditis*, secondary (central) hypothyroidism; Pregnancy, breastfeeding or wish to become pregnant within 2 years; Current/past atrial fibrillation; Frequent ventricular extrasystole (=doublet, trigeminy, bigeminy or (non-sustained) ventricular tachycardia) in the past or on current ECG.