Allan-Herndon-Dudley SyndromePhase 2NCT02396459
Triac Trial II in MCT8 Deficiency Patients
A Phase 2 study testing Tiratricol in people with Allan-Herndon-Dudley Syndrome, run by Rare Thyroid Therapeutics International AB at 5 sites in 4 countries.
Trial summary
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)). Read more about this study
- Who is it for?
- Ages Up to 30 months, men only
- Conditions the study is for
- Allan-Herndon-Dudley Syndrome
- What is being tested?
- Tiratricol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 7 Dec 2020to 18 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 months
- Men only
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
United States2 sites
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University (OHSU) Doernbecher Childrens Hospital
Portland, Oregon, 97239
Czechia1 site
Charles University and Motol University Hospital; The department of peadiatrics of the 2nd faculty of medicine
Prague, 15006
Germany1 site
Charité - Universitätsmedizin Berlin Institut fur experimental paediatrische endokrinologie
Berlin, 13353
About this study
Official title: Tiratricol Treatment of Children With Monocarboxylate Transporter 8 Deficiency: Triac Trial II
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.
Read the detailed description
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.
- Conditions
- Allan-Herndon-Dudley Syndrome
- Being tested
- Tiratricol
- Keywords
- Triac, MCT8, MCT8 deficiency, Allan-Herndon-Dudley Syndrome
- Medical subject headings
- Allan-Herndon-Dudley syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiratricolDrug
Also called Triac, Teatrois
Tiratricol, individually titrated dose
| Study group | Role | What they receive |
|---|---|---|
| MCT8 deficient patients | Experimental | Tiratricol (Triac) treatment Receives: Drug: Tiratricol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gross Motor Function Measure 88 (GMFM 88) total score
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.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Bayley Scales of Infant Development III Gross Motor Skill Domain score
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
Measured: 96 weeks, Year 3, Year 4 and Year 5
Secondary outcomes (8)
GMFM-88 individual item score 10 and 24.
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).
Measured: 96 weeks, Year 3, Year 4 and Year 5
Bayley Scales of Infant Development III score.
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.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Serum T3 concentrations
Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Tissue-specific markers of thyroid state: serum sex-hormone binding globulin concentrations for liver
Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Tissue-specific markers of thyroid state: serum creatine kinase concentrations for muscles
Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Tissue-specific markers of thyroid state: serum creatinine concentrations for kidneys
Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Blood pressure
Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Body weight
Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features.
Measured: 96 weeks, Year 3, Year 4 and Year 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2015 (estimated)
- Study start7 Dec 2020
- Primary completion18 Jul 2027 (estimated)
- Study completion18 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allan-Herndon-Dudley SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rare Thyroid Therapeutics International AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Erasmus Medical Center
- Responsible party
- Sponsor
- Investigators
- W.E. Visser, MD, PhD, Principal investigator, Erasmus Medical CenterKristina Sjöblom Nygren, MD, Study director, Rare Thyroid Therapeutics International ABLindsey Nicol, Principal investigator, Oregon Health& Science University (OHSU) Doernbecher Childrens HospitalJan Lebl, Principal investigator, Charles University and Motol University HospitalHeiko Krude, Principal investigator, Charité - Universitätsmedizin Berlin Institut fur experimental paediatrische endokrinologieAndrew Bauer, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02396459
- Sponsor's protocol ID
- MCT8-2019-2
- Status last verified
- Feb 2026
- First submitted
- 7 Mar 2015
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Because of the rarity of MCT8 deficiency and the small number of patients in this trial, individual patient data beyond what is reported in the upcoming manuscript will not be shared to safeguard patient privacy.
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tiratricol Treatment of Children With Monocarboxylate Transporter 8 Deficiency: Triac Trial II
- ClinicalTrials.gov ID
- NCT02396459
- Acronym / sponsor ID
- MCT8-2019-2
- Conditions
- Allan-Herndon-Dudley Syndrome
- Keywords
- Triac, MCT8, MCT8 deficiency, Allan-Herndon-Dudley Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Rare Thyroid Therapeutics International ABIndustry (pharma, biotech, devices)
- Collaborators
- Erasmus Medical Center
- Study start
- 7 Dec 2020 (actual)
- Primary completion
- 18 Jul 2027 (estimated)
- Study completion
- 18 Aug 2027 (estimated)
- First posted
- 24 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MCT8 deficient patients | Experimental | Drug: TiratricolTiratricol (Triac) treatment |
Who may qualify
- Ages
- Up to 30 months
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TiratricolAlso: Triac, TeatroisTiratricol, individually titrated dose | Drug | MCT8 deficient patients |
Primary outcome
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.
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
8 secondary outcomes
GMFM-88 individual item score 10 and 24.
Time frame: 96 weeks, Year 3, Year 4 and Year 5
Bayley Scales of Infant Development III score.
Time frame: 96 weeks, Year 3, Year 4 and Year 5
Serum T3 concentrations
Time frame: 96 weeks, Year 3, Year 4 and Year 5
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
Tissue-specific markers of thyroid state: serum creatine kinase concentrations for muscles
Time frame: 96 weeks, Year 3, Year 4 and Year 5
Tissue-specific markers of thyroid state: serum creatinine concentrations for kidneys
Time frame: 96 weeks, Year 3, Year 4 and Year 5
Blood pressure
Time frame: 96 weeks, Year 3, Year 4 and Year 5
Body weight
Time frame: 96 weeks, Year 3, Year 4 and Year 5
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Individual participant dataSharing planned: No. Because of the rarity of MCT8 deficiency and the small number of patients in this trial, individual patient data beyond what is reported in the upcoming manuscript will not be shared to safeguard patient privacy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
W.E. Visser, MD, PhD principal investigator
Erasmus Medical Center
Kristina Sjöblom Nygren, MD study director
Rare Thyroid Therapeutics International AB
Lindsey Nicol principal investigator
Oregon Health& Science University (OHSU) Doernbecher Childrens Hospital
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tiratricol in people with Allan-Herndon-Dudley Syndrome, run by Rare Thyroid Therapeutics International AB at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Czechia, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gross Motor Function Measure 88 (GMFM 88) total score (time frame: 96 weeks, Year 3, Year 4 and Year 5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2026.