Overview

This trial is active, not recruiting.

Condition allan-herndon-dudley syndrome
Treatment triac
Phase phase 2
Sponsor Erasmus Medical Center
Collaborator ZonMw: The Netherlands Organisation for Health Research and Development
Start date October 2014
End date January 2017
Trial size 35 participants
Trial identifier NCT02060474, 2014-000178-20, MCT8-2014-1

Summary

This therapeutical trial will be conducted in patients with the Allan-Herndon-Dudley Syndrome (AHDS), which is mutations in MCT8.

MCT8 is a thyroid hormone (TH) transporter which is crucial for the transport of TH from the blood into different tissues. Dysfunction of MCT8 results in a lack of TH (hypothyroidism) in tissues that depend on MCT8 for TH uptake. This local hypothyroidism in the brain of these patients causes severe psychomotor retardation.

In addition, TH serum parameters are highly abnormal in AHDS: high T3, low T4 and normal TSH levels. The high serum T3 levels cause local hyperthyroidism in tissues that do not depend on MCT8 for cellular transport of TH, resulting in a low body weight and reduced muscle mass.

Currently, no adequate treatment is available for the AHDS. A T3 analog that does not depend on MCT8 for its cellular entry could, at least partially, restore the abnormalities found in AHDS. Several in vivo, in vitro and animal studies have shown that the T3 analog Triac is a very promising candidate:

1. Triac binds to the same TH receptors as T3;

2. Cellular uptake of Triac does not depend on functional MCT8. Hence, in AHDS patients Triac will also be available in tissues that require functional MCT8 for TH uptake, e.g. the brain;

3. In vitro studies have shown that neuronal cells differentiate equally well in the presence of either Triac or T3;

4. In Mct8 deficient mice, Triac is taken up by the brain and suppresses serum TSH levels; consequently, serum T3 and T4 levels were lowered;

5. Triac is the treatment of choice in patient with the resistance to thyroid hormone (RTH) syndrome. Patient with RTH have high serum TSH and thyroid hormone levels, which shows strong similarities to the profile found in AHDS patients; the longstanding experience with Triac in RTH indicates its safety and tolerability .

Thus, Triac treatment could result in normalization of the abnormal serum TH values in AHDS patients. Furthermore, Triac could replace the function of T3 in tissues that depend on MCT8 for TH uptake (e.g. brain).

The current trial will investigate if Triac treatment in ADHS patients

1. reduces the toxic effects of the high T3 levels

2. restores the local TH deficiency in brain.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
all AHDS recruited for this study will be located in the experimental arm and will receive the investigational medicinal product Triac. The Triac dose will be individually titrated to the optimal dose level.
triac Tiratricol, Téatrois, TA3
Triac is a naturally occuring T3 metabolite with similar bioactivity and receptor binding profile.

Primary Outcomes

Measure
serum thyroid function tests
time frame: Participants will be evaluated with an expected average of 2 weeks during months 1-3 of the trial. During months 4-12 participants will be evaluated with an expected average of 6 weeks.
general clinical examination
time frame: Participants will be evaluated with an expected average of 2 weeks during months 1-3 of the trial. During months 4-12 participants will be evaluated with an expected average of 6 weeks.
tissue-specific markers of thyroid state
time frame: Participants will be evaluated with an expected average of 2 weeks during months 1-3 of the trial. During months 4-12 participants will be evaluated with an expected average of 6 weeks.

Secondary Outcomes

Measure
Motor function, using the Gross Motor Function Measure
time frame: 12 months
Cognitive function using the Bayley Scales of Infant Development III
time frame: 12 months
Adaptive behavior by the Vineland adaptive behavior scale
time frame: 12 months

Eligibility Criteria

Male participants up to 99 years old.

Inclusion Criteria: - clinically relevant mutation in the MCT8 gene, resulting in the clinical phenotype of AHDS. Exclusion Criteria: - Major illness or recent major surgery (within 4 weeks) unrelated to AHDS - Patients who are participating in ongoing RCTs of therapeutic interventions (including clinical trials of investigational medicinal products); - Known allergy to components in Triac tablets; - Patients that have any contra-indication for Triac treatment.

Additional Information

Official title Thyroid Hormone Analog Therapy of Patients With Severe Psychomotor Retardation Caused by Mutations in the MCT8 Thyroid Hormone Transporter: The Triac Trial.
Principal investigator W.E. Visser, dr,
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Erasmus Medical Center.