Trial record 2 of 119 for:    "Renpenning syndrome" OR "Mental Retardation, X-Linked"

Triac Trial in MCT8 Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Erasmus Medical Center
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
W. Edward Visser, Erasmus Medical Center
ClinicalTrials.gov Identifier:
NCT02060474
First received: February 5, 2014
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

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.

Condition Intervention Phase
Allan-Herndon-Dudley Syndrome
Drug: Triac
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Thyroid Hormone Analog Therapy of Patients With Severe Psychomotor Retardation Caused by Mutations in the MCT8 Thyroid Hormone Transporter: The Triac Trial.

Resource links provided by NLM:


Further study details as provided by Erasmus Medical Center:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    Serum TH parameters will be determined to assess the effect of Triac

  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Motor function, using the Gross Motor Function Measure [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    motor function will be measured during the first visit of the trial (T0) and after 12 months (T12) reflecting the effect of Triac over a 1 year period

  • Cognitive function using the Bayley Scales of Infant Development III [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    cognitive function will be measured during the first visit of the trial (T0) and after 12 months (T12) reflecting the effect of Triac over a 1 year period

  • Adaptive behavior by the Vineland adaptive behavior scale [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    adaptive behavior will be measured during the first visit of the trial (T0) and after 12 months (T12) reflecting the effect of Triac over a 1 year period


Other Outcome Measures:
  • Monitoring of adverse effects. [ Time Frame: up to one year (= whole study period) ] [ Designated as safety issue: Yes ]
    Family members and caregivers of the included patients will be asked to report all adverse effects to one of the investigators.

  • A routine trans-thoracic cardiac ultrasound [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    the effects of Triac on the heart function will be measured using cardiac ultrasonography during the first visit (T0) and after 12 months (T12), reflecting the effect of Triac on the heart over a period of 1 year.

  • ECG [ 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. ] [ Designated as safety issue: Yes ]
    The effect of Triac on the heart rhythm will be assessed with an ECG

  • Bone Mineral Density [ Time Frame: motor function will be measured during the first visit of the trial (T0) and after 12 months (T12) reflecting the effect of Triac over a 1 year period ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: May 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AHDS patients
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.
Drug: Triac
Triac is a naturally occuring T3 metabolite with similar bioactivity and receptor binding profile.
Other Name: Tiratricol, Téatrois, TA3

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02060474

Contacts
Contact: W.E. Visser, dr. 0031104087209 w.e.visser@erasmusmc.nl

Locations
Netherlands
Erasmus Medical Center Not yet recruiting
Rotterdam, South-Holland, Netherlands, 3000 CA
Contact: W.E. Visser, dr.    0031104087209    w.e.visser@erasmusmc.nl   
Principal Investigator: W.E. Visser, dr.         
Sponsors and Collaborators
Erasmus Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: W.E. Visser, dr, Erasmus Medical Center
  More Information

No publications provided

Responsible Party: W. Edward Visser, Dr., Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02060474     History of Changes
Other Study ID Numbers: MCT8-2014-1, 2014-000178-20
Study First Received: February 5, 2014
Last Updated: February 11, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Erasmus Medical Center:
Allan-Herndon-Dudley Syndrome
MCT8
Triac
Therapeutic Trial

Additional relevant MeSH terms:
Mental Retardation, X-Linked
Syndrome
Muscle Hypotonia
Muscular Atrophy
Disease
Pathologic Processes
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Atrophy
Pathological Conditions, Anatomical
Intellectual Disability
Neurobehavioral Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Guaifenesin
Phenylpropanolamine
Chlorpheniramine, phenylpropanolamine drug combination
Expectorants
Respiratory System Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014