Treatment of TK2 Deficiency With Thymidine and Deoxycytidine

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-16

Study Completion Date

2026-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Patients with confirmed mitochondrial DNA depletion syndrome 2 (thymidine kinase 2 \[TK2\] deficiency) have reduced levels of nucleotides (deoxythymidine monophosphate and deoxycytidine monophosphate) for mitochondrial DNA synthesis. This results in mitochondrial DNA depletion syndrome (i.e less number of functional mitochondrial DNA). Patients with confirmed TK2 deficiency will be treated with open label deoxythymidine (dThd) and deoxycytidine (dCyt), which are nucleotide precursors, with the expectation that the cells could make additional mitochondrial DNA. This in turn may help reduce the clinical symptoms.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy

NCT02858908

Myotonic Dystrophy 1

COMPLETED PHASE2

A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease

NCT02473445

Mitochondrial Diseases

TERMINATED PHASE2

RG2133 (2',3',5'-Tri-O-Acetyluridine) in Mitochondrial Disease

NCT00060515

Mitochondrial Diseases

TERMINATED PHASE1

Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

NCT03692312

Congenital Myotonic Dystrophy

COMPLETED PHASE2/PHASE3

Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy

NCT05004129

Congenital Myotonic Dystrophy

RECRUITING PHASE2/PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Mitochondrial are responsible for the production of cellular energy. Mitochondria contain DNA which is the encoding system ( "recipe") for making the proteins that allow the mitochondria to function. Reduced amount of mitochondrial DNA, caused by genetic mutations in certain genes, Mitochondrial DNA Depletion Syndrome. This can result in symptoms; such as fatigue, weakness, and deficiencies in various body systems. TK2 deficiency is considered a mitochondrial depletion syndrome. Patients with TK2 deficiency have weakness and walking difficulty. They also have depleted levels of chemicals (phosphorylated deoxythymidine and deoxycytidine) used to make mitochondrial DNA. Based on previous studies with a similar compound, patients reported more energy and better motor skills.

Eligible patients include those with genetic mutations in the TK2 gene who are willing to attend several outpatient visits, and have motor skills testing, neurological exam by doctor, and blood samples.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mitochondrial DNA Depletion Syndrome 2 Myopathic Type Thymidine Kinase 2 Deficiency

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Open label treatment with thymidine and deoxycytidine

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Open label thymidine and deoxycytidine

All patients will receive open label thymidine and deoxycytidine

Group Type EXPERIMENTAL

Thymidine

Intervention Type DRUG

Mitochondrial DNA nucleotide precursors. Dose escalation: 130mg/kg/day x 14 days, 260 mg/kg/day x 14 days, and 400mg/kg/day as tolerated. Compounds are taken orally and divided into 3 doses daily.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Thymidine

Mitochondrial DNA nucleotide precursors. Dose escalation: 130mg/kg/day x 14 days, 260 mg/kg/day x 14 days, and 400mg/kg/day as tolerated. Compounds are taken orally and divided into 3 doses daily.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Deoxycytidine

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Genetically confirmed diagnosis of TK2 deficiency
* Deemed by principle investigator to be symptomatic with TK2 deficiency
* Single gene disease; absence of polygenic disease
* Hematocrit within normal range for age group
* Patient or patient's guardian able to consent and comply with protocol requirements
* Presence of caregiver to ensure study compliance (if needed)
* Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator)
* Abstention from use of other investigational medications or other medications according to the study investigator

Exclusion Criteria

* Clinical history of bleeding or abnormal prothrombin time (PT)/partial thromboplastin time (PTT)
* Hepatic insufficiency with liver function tests (LFTs) greater than two times normal
* Renal insufficiency requiring dialysis
* Any other concurrent inborn errors of metabolism
* Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis

Eligible Sex

ALL

Accepts Healthy Volunteers

No