LT4/LT3 Combination Therapy Versus LT4 Monotherapy in Patients With Autoimmune Hypothyroidism.

• Status: Recruiting
• Trial end date: 2026-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M. Medici
• Collaborators: ACE Pharmaceuticals BV; ZonMw: The Netherlands Organisation for Health Research and Development

Criteria

Inclusion Criteria:

• 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 Criteria:

• Congenital hypothyroidism, hypothyroidism after (sub)acute thyroiditis, secondary (central) hypothyroidism

• 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.

• Pregnancy, breastfeeding or wish to become pregnant within 2 years.

• 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.

• Functional or structural abnormal heart (e.g., cardiomyopathy or valve disease)

• Recent acute coronary syndrome or unstable angina pectoris (<4 weeks)

• Current/past atrial fibrillation

• Current conduction disorder on ECG (i.e, QRS>100 ms or prolonged QTc (women≥460 ms and men≥450 ms)).

• Frequent ventricular extrasystole (=doublet, trigeminy, bigeminy or (non-sustained) ventricular tachycardia) in the past or on current ECG.

• 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)

• 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)