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NCT Number: NCT02396459

Triac Trial II in MCT8 Deficiency Patients

This study will investigate the effect of treatment with tiratricol (also called Triac) in young boys (≤30 months) with MCT8 deficiency (also called the Allan-Herndon-Dudley syndrome (AHDS)). The hypothesis tested is that treatment with tiratricol will have a beneficial effect on the hypothyroid state in the brain as well as the hyperthyroid state in peripheral organs and tissues in these patients. Patients will initially be treated for 96 weeks with tiratricol, treatment effect on neurodevelopment impairment caused by hypothyroidism and peripheral thyrotoxicosis will be evaluated after 96 weeks treatment. Patients will be offered to continue on treatment for an additional 3 years.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Allan-Herndon-Dudley Syndrome

Age range

Up to 30 month

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Charles University and Motol University Hospital; The department of peadiatrics of the 2nd faculty of medicine, Prague, Czechia

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About this study

This therapeutic trial will be conducted in patients with MCT8 deficiency (also called Allan-Herndon-Dudley Syndrome (AHDS)), which is due to mutations in monocarboxylate transporter (MCT)8. MCT8 is a thyroid hormone transporter which is crucial for the transport of thyroid hormone from the blood into different tissues. Defective MCT8 results in a lack of thyroid hormone (hypothyroidism) in tissues that are dependent on MCT8 for thyroid hormone uptake, such as the brain. Hypothyroidism in the brain results in severe intellectual and motor disability. Another important feature of this disease is the high serum T3 concentrations in the blood. This results in hyperthyroidism in tissues that are not dependent on MCT8 for their thyroid hormone supply. As a result, patients with MCT8 deficiency have clinical features of thyrotoxicosis such as low body weight, elevated heart rate and reduced muscle mass.

Preclinical studies have shown that the T3 analogue tiratricol is transported into cells in an MCT8-independent manner. In animal models mimicking MCT8 deficiency, Triac has been shown to normalize brain development if administrated during early postnatal life.

Recently, Triac Trial I (NCT02060474) has shown that tiratricol treatment in patients with MCT8 deficiency improves key clinical and biochemical features caused by the toxic effects of the high T3 concentrations. No drug related serious adverse events have occurred during Triac Trial I.

This study will investigate the effect of treatment with tiratricol in young boys (≤30 months) with MCT8 deficiency (also called the Allan-Herndon-Dudley syndrome (AHDS)). The hypothesis tested is that treatment with tiratricol will have a beneficial effect on the hypothyroid state in the brain as well as the hyperthyroid state in peripheral organs and tissues in these patients. Patients will initially be treated for 96 weeks with tiratricol, treatment effect will be evaluated after 96 weeks. After the 96 week treatment period, patients will enter Part II of the trial, evaluating long-term treatment. Patients will be followed for an additional 3 years and treatment effect will be evaluated after 3 years, 4 years and 5 years respectively from start of treatment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed and dated informed consent form from the parents or legal guardian.
  • Parents stated willingness to comply with all study procedures and availability for the duration of the study.
  • The participant should be aged between 0 and 30 months on the day of inclusion.
  • The participant should be male and have a pathogenic mutation in the MCT8 gene.

Exclusion criteria

  • Previous treatment with tiratricol.
  • Previous treatment with LT4 and/or PTU and/or other anti-thyroid medication for a period longer than three months. Patients previously treated with LT4 for a shorter period than 3 months may be included in the study (baseline visit) six weeks (or longer) after last dose of LT4 if two consecutive analyses show stable TFT*. Patients treated with PTU and/or other anti-thyroid medication for a shorter period than three months may be included in the study (baseline visit) six weeks (or longer) after last dose.
  • Major illness or recent major surgery (within four weeks of baseline visit 1) unrelated to MCT8 deficiency.
  • Known allergic reactions to components of the IMP. Patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose or galactose (the IMP contains lactose).
  • Treatment with another investigational drug or participation in other interventional trial within three months prior to baseline visit 1.

Treatment and study plan

Tiratricol

Drug

Tiratricol, individually titrated dose

Other names: Triac, Teatrois

Primary outcomes

  1. Gross Motor Function Measure 88 (GMFM 88) total score

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    To evaluate the effects of tiratricol on neurodevelopment in young MCT8 deficiency patients, measured by the Gross Motor Function Measure (GMFM)-88 assessment. Potential result values range from 0 to 100%, the latter being representative for a 4-year old healthy child. A high score is equivalent to better/more neurodevelopment and is therefore a better outcome than a low score.

  2. Bayley Scales of Infant Development III Gross Motor Skill Domain score

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    To evaluate the effect of tiratricol treatment on neurodevelopment measured by the Bayley Scales of Infant Development (BSID-III) Gross Motor Skill Domain score. Potential total raw scores range from 0-72, and can be age-adjusted before analysis. A high score is equivalent to better/more neurodevelopment and is therefore a better outcome than a low score

Secondary outcomes

  1. GMFM-88 individual item score 10 and 24.

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    GMFM-88 individual item score 10 ("lifts head upright") and item score 24 ("sit on mat"), GMFM Domain B (Sitting) - summary score of all items 18-37 ; Motor milestone responder analysis of Section 2 of the Hammersmith Infant Neurological Examination (HINE).

  2. Bayley Scales of Infant Development III score.

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    To evaluate the effect of tiratricol treatment on neurodevelopment measured by the Bayley Scales of Infant Development (BSID-III). Five subscales of this assessment will be used: Cognitive, Receptive communication, Expressive communication, Fine motor and Gross motor. Potential total raw scores range from 0-91, 0-49, 0-48, 0-66 and 0-72 respectively, and can be age-adjusted before analysis. A high score is equivalent to better/more neurodevelopment and is therefore a better outcome than a low score. This holds true for all subscales.

  3. Serum T3 concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.

  4. Tissue-specific markers of thyroid state: serum sex-hormone binding globulin concentrations for liver

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.

  5. Tissue-specific markers of thyroid state: serum creatine kinase concentrations for muscles

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.

  6. Tissue-specific markers of thyroid state: serum creatinine concentrations for kidneys

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.

  7. Blood pressure

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.

  8. Body weight

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.

Other outcomes

  1. Patient Quality of Life by Infant Toddler Quality of Life Questionnaire (ITQoL)

    Time frame: 96 weeks and Year 5

    To evaluate patient´s quality of life (QoL) by Infant Toddler Quality of Life (ITQoL-SF-47) questionnaire. Item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). A high score is equivalent to better parent-reported outcomes and is therefore a better outcome than a low score.

  2. Parent Quality of Life by Parenting Stress index (PSI-4 SF)

    Time frame: 96 weeks and Year 5

    To evaluate parent's quality of life (QoL) by Parenting Stress Index (PSI-4 SF) questionnaire. Results are given as raw scores, percentiles and T scores, where percentiles are the primary interpretive framework. Results from 16th - 84th percentile = Normal range, 85th - 89th Percentile = High range, 90th Percentile or higher = Clinically significant range.

  3. Evaluate the effect of tiratricol treatment on neurological symptoms (Hammersmith Infant Neurological Exam, HINE)

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Hammersmith Infant Neurological Exam (HINE)

  4. Evaluate the effect of tiratricol treatment on brain function (optional) (EEG)

    Time frame: 96 weeks

    Brain function outcome (optional) evaluated by EEG

  5. Evaluate the effect of tiratricol treatment on brain function (optional) (BERA)

    Time frame: 96 weeks

    Brain function outcome (optional) evaluated by Brainstem Evoked Response Audiogram (BERA)

  6. Evaluate the effect of tiratricol treatment on brain function (optional) (VEP)

    Time frame: 96 weeks

    Brain function/brain imaging outcome (optional) evaluated by Visual Evoked Potentials (VEP)

  7. Evaluate the effect of tiratricol treatment on brain imaging (optional)

    Time frame: 96 weeks

    Brain imaging outcome (optional) evaluated by MRI/MRS - in patients where this examination is scheduled as part of a clinical praxis (at the discretion of the investigator)

  8. Estimate the elimination half-life of tiratricol in young children, reported in hours (optional and provided a medical reason prevails).

    Time frame: From baseline to end of the study

    Measurement of serum T3 concentrations of tiratricol as part of pharmacokinetic profile (optional and provided a medical reason prevails)

  9. Estimate the maximum serum concentration of tiratricol in young children, reported in nmol/L (optional and provided a medical reason prevails).

    Time frame: From baseline to end of the study

    Measurement of serum T3 concentrations of tiratricol as part of pharmacokinetic profile (optional and provided a medical reason prevails)

  10. Evaluate the occurrence of episodes of tachycardia caused by the thyrotoxicosis.

    Time frame: 96 weeks and Year 5

    Evaluation of cardiac rhythm and number of episodes of tachycardia with 24 hour Holter ECG.

  11. Evaluate the occurrence of premature atrial complexes (PACs) caused by the thyrotoxicosis.

    Time frame: 96 weeks and Year 5

    Evaluation of occurrence of PACs with 24 hour Holter ECG.

  12. Evaluate the occurrence of other arrhythmias caused by the thyrotoxicosis.

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Descriptive evaluation of occurrence of other arrhythmias with 24 hour Holter ECG.

  13. Evaluate the occurrence of structural cardiac anomalies in patients

    Time frame: 96 weeks and Year 5

    Evaluation of the occurrence of structural cardiac anomalies using routine trans-thoracic cardiac ultrasound.

  14. Number of participants with Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs)

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE is defined as an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Severity was graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). TEAEs are defined as AEs with onset on or after the time of initiation of study drug administration.

  15. Serum free T4 (FT4) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on FT4 concentrations to ensure patient safety.

  16. Serum total T4 (T4) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on T4 concentrations to ensure patient safety.

  17. Serum tiratricol concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate tiratricol concentrations in serum, as estimated based on measured T3 concentrations in serum.

  18. Serum thyroid stimulating hormone (TSH) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on TSH concentrations to ensure patient safety.

  19. Serum reverse T3 (rT3) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on rT3 concentrations to ensure patient safety.

  20. Serum Alanine (Amino) Transaminase (ALAT) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on ALAT concentrations to ensure patient safety.

  21. Serum Aspartate (Amino) Transaminase (ASAT) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on ASAT concentrations to ensure patient safety

  22. Serum gamma-glutamyl transferase (gGT) concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on gGT concentrations to ensure patient safety.

  23. Serum alkaline phosphatase concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on alkaline phosphatase concentrations to ensure patient safety.

  24. Serum albumin concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on albumin concentrations to ensure patient safety.

  25. Serum urea concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on urea concentrations to ensure patient safety.

  26. Serum sodium concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on sodium concentrations to ensure patient safety.

  27. Serum potassium concentrations

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on potassium concentrations to ensure patient safety.

  28. White blood cell total and differential count

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on white blood cell total and differential count to ensure patient safety.

  29. Red blood cell count

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on red blood cell count to ensure patient safety.

  30. Platelet count

    Time frame: 96 weeks, Year 3, Year 4 and Year 5

    Evaluate the effect of tiratricol on platelet cell count to ensure patient safety.

Sponsors and collaborators

Lead sponsor

Rare Thyroid Therapeutics International AB

Industry

Collaborators

  • Erasmus Medical Center

Registry information

Official study title

Tiratricol Treatment of Children With Monocarboxylate Transporter 8 Deficiency: Triac Trial II

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
Mar 24, 2015
Registry last updated
Feb 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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