Rescue of Infants With MCT8 Deficiency (DITPA)

Monocarboxylate Transporter 8 (MCT8) deficiency (that is also known as Allan-Herndon-Dudley syndrome) is a rare X-linked inherited disorder of brain development that causes severe intellectual disability and problems with movement. This condition, which occurs almost exclusively in males, disrupts development from before birth.

Study Overview

• Status: Available
• Conditions: Mct8 (Slc16A2)-Specific Thyroid Hormone Cell Transporter Deficiency
• Intervention / Treatment: Drug: Diiodothyropropionic acid (DITPA)

Detailed Description

MCT8 deficiency (that is also known as Allan-Herndon-Dudley syndrome) is a rare X-linked inherited disorder of brain development that causes severe intellectual disability and problems with movement. This condition, which occurs almost exclusively in males, disrupts development from before birth. There is no sucking reflex and the child has marked hypotonia. Developmentally, unlike normal infants, affected males are unable to turn over from belly to back. Individuals with identical mutations have identical phenotypes and all individuals, regardless of the phenotype have severe neuropsychological impairment. Diagnosis is confirmed by demonstration of a mutation in the MCT8 gene (1,2).

MCT8-specific thyroid hormone cell-membrane transporter deficiency is characterized by severe cognitive deficiency, infantile hypotonia, diminished muscle mass and generalized muscle weakness, progressive spastic quadriplegia, joint contractures, and dystonic and/or athetoid movement with characteristic paroxysms or kinesigenic dyskinesias. Seizures occur in about 25% of cases. Most affected males never sit or walk independently or lose these abilities over time; most never speak or have severely dysarthric speech (1). Brain MRI obtained in the first few years of life shows transient delayed myelination, which improves by age four years (3). Although psychomotor findings observed in affected males do not occur in heterozygous females, the latter often have thyroid test abnormalities intermediate between affected and normal individuals.

• Study Type: Expanded Access
• Expanded Access Type: Individual Patients; Treatment IND/Protocol
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Available
      • University of Miami, Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 3 days (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Genetic Confirmation: Male fetus or fetuses (including monozygotic twin pregnancies) must have a confirmed MCT8 gene mutation.
• Family History: A previously born child or children with a severe, typical phenotype and an MCT8 gene mutation identical to that of the fetus.
• Alternatively, the mother or a sister must have a relative with a known MCT8 defect.
• Parental Decision: Parental refusal to terminate the pregnancy despite the diagnosis of MCT8 deficiency.
• Compliance and Availability: Willingness of the parents to comply with all study procedures and ensure availability for the duration of the study.

Exclusion Criteria:

• Pregnancy-Related Factors: Dizygotic (non-identical) twin pregnancy (unless only one fetus is confirmed with the MCT8 mutation, and the unaffected fetus will not be treated).

Parental decision to terminate the pregnancy.

• Maternal Medical Conditions: Hyperthyroidism requiring treatment. Significant liver or kidney insufficiency. Congestive heart failure. Hyperemesis gravidarum unresponsive to treatment.

• Significant cardiac conditions, including:
• Atrial fibrillation or other arrhythmias.
• Unstable angina.
• Coronary heart disease.
• Medications:

Current use of sympathomimetic therapy. Anticoagulant therapy. Use of Cytochrome P450 2C9 (CYP2C9) inhibitors with a narrow therapeutic index.

• Other Factors: Major illness or recent major surgery within four weeks of baseline visit 1, unrelated to MCT8 deficiency.

Study Plan

How is the study designed?

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prenatal Treatment Protocol; This protocol involves administering DITPA to pregnant women diagnosed with fetuses exhibiting MCT8 deficiency. Early initiation of treatment is critical as it targets the crucial period of neurological development, aiming to mitigate severe deficits typically associated with MCT8 deficiency. Following birth, the child will continue to receive treatment until the age of 3 years. All elements of this clinical protocol are essential and directly applicable to this arm of the study.	Drug: Diiodothyropropionic acid; Drug Administration; Other Names: DITPA
Active Comparator: Postnatal Treatment Options; 2(a) Immediate Post-Birth Treatment: This approach is designated for neonates who were diagnosed with MCT8 deficiency in utero but were not included in ARM 1. Treatment with DITPA will commence within the first 24 hours post-birth. This prompt initiation is intended to capitalize on the immediate postnatal period to optimize therapeutic outcomes.; 2(b) Delayed Post-Birth Treatment: This option is for neonates diagnosed with MCT8 deficiency after birth. Treatment will begin several days post-birth, ensuring that those not identified during the prenatal period still receive early intervention following diagnosis. This strategy is essential for improving long-term endocrine and neurodevelopmental health.; Only relevant sections of the clinical protocol for AHDS (MCT8 deficiency) will apply to both ARM 2(a) Immediate Post-Birth Treatment and ARM 2(b) Delayed Post-Birth Treatment.	Drug: Diiodothyropropionic acid; Drug Administration; Other Names: DITPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychomotor development of a child with MCT8 deficiency	Neuropsychomotor development of a child with MCT8 deficiency near-normal compared to standardized developmental assessments.	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correct the abnormal thyroid function tests and hypermetabolism in newborn and infants with MCT8 deficiency by maternal and infant treatment with the thyroid hormone analogue, DITPA	T3 concentration decreases from baseline, at the 1-year post-partum visit; T4 concentration increases from baseline, at the 1-year post-partum visit; TSH in range or suppressed, at the 1-year post-partum visit; Incidence of adverse events (AE) comparable to general population.	1 Year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correction of peripheral hypermetabolism and normalize thyroid function tests in infants diagnosed with MCT8 deficiency post birth, who were unable to receive prenatal treatment with DITPA.	To correct peripheral hypermetabolism and normalize thyroid function tests in infants diagnosed with MCT8 deficiency post birth, who were unable to receive prenatal treatment with DITPA. This aim seeks to address the metabolic disturbances that typically accompany MCT8 deficiency, utilizing DITPA treatment to stabilize the infants' metabolic state and thyroid function as soon after birth as possible. This intervention aims for mitigating the long-term physiological impacts of the deficiency and supporting optimal health outcomes.	1 Year

Collaborators and Investigators

• Sponsor: Roy E. Weiss, M.D.
• Investigators: Principal Investigator: Roy E Weiss, M.D., University of Miami

Study record dates

Study Major Dates

• Study Start: April 3, 2018
• Primary Completion: April 1, 2027
• Study Completion: April 1, 2027

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (Actual): October 29, 2019

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Allan-Herndon-Dudley syndrome; 3,5-diiodothyropropionic acid
• Other Study ID Numbers: 20180087

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No