Triac Trial II in MCT8 Deficiency Patients

NCT ID: NCT02396459

Last Updated: 2024-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-07

Study Completion Date

2026-06-30

Brief Summary

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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 2 years.

Detailed Description

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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 2 years and treatment effect will be evaluated after 3 years and 4 years respectively from start of treatment.

Conditions

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Allan-Herndon-Dudley Syndrome

Keywords

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Triac MCT8 MCT8 deficiency Allan-Herndon-Dudley Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MCT8 deficiency patients

Triac treatment

Group Type EXPERIMENTAL

Triac

Intervention Type DRUG

Triac, individually titrated dose

Interventions

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Triac

Triac, individually titrated dose

Intervention Type DRUG

Other Intervention Names

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Tiratricol Teatrois

Eligibility Criteria

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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.
Maximum Eligible Age

30 Months

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Erasmus Medical Center

OTHER

Sponsor Role collaborator

Rare Thyroid Therapeutics International AB

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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W.E. Visser, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Kristina Sjöblom Nygren, MD

Role: STUDY_DIRECTOR

Rare Thyroid Therapeutics International AB

Stephen LaFranchi_Nicol

Role: PRINCIPAL_INVESTIGATOR

Oregon Health& Science University (OHSU) Doernbecher Childrens Hospital

Jan Lebl

Role: PRINCIPAL_INVESTIGATOR

Charles University and Motol University Hospital

Heiko Krude

Role: PRINCIPAL_INVESTIGATOR

Charité - Universitätsmedizin Berlin Institut fur experimental paediatrische endokrinologie

Andrew Bauer, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Oregon Health & Science University (OHSU) Doernbecher Childrens Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

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

Prague, , Czechia

Site Status

Charité - Universitätsmedizin Berlin Institut fur experimental paediatrische endokrinologie

Berlin, , Germany

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

Countries

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United States Czechia Germany Netherlands

Other Identifiers

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MCT8-2019-2

Identifier Type: -

Identifier Source: org_study_id