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Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome

NCT04802707 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 200

Last updated 2025-05-31

No results posted yet for this study

Summary

Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis. MDS are phenotypically heterogeneous and usually classified as myopathic, encephalomyopathic, hepatocerebral or neurogastrointestinal.

No efficacious therapy is available for any of these disorders. Affected individuals should have a comprehensive evaluation to assess the degree of involvement of different systems. Treatment is directed mainly toward providing symptomatic management. No treatment for MDS.

Clinical trials studies and in vitro/in vivo research studies showed that the enhancement of the salvage pathway by increasing the availability of deoxyribonucleosides needed for each specific genetic defect prevents mtDNA depletion.

Early recognition and immediate therapy to restore mitochondrial function could potentially improve clinical course.

Confirming the benefit of deoxynucleosides as a safe and potentially efficacious therapy, will lead to the availability of the first specific and effective treatment for Mitochondria Depletion Disorders.

In this phase II Trial a mix of Deoxynucleosides Pyrimidine (Deoxycytidine dC and Deoxythymidine dT) will be used as early treatment of MDS.

The dose used has been already used in other clinical trials, and appears to effective and well-tolerated. The subjects included are children (0-18Y), with positive MDS diagnosis and express mutations in one of the following genes: POLG, POLG2, C10orf2, RRM2B, MPV17, SUCLA2, SUCLG1, FBXL4, DTYMK. Subjects with MDS expressing neurological phenotypes dysfunction.

Conditions

  • Mitochondrial Diseases
  • Mitochondrial Encephalomyopathy
  • Mitochondrial Encephalopathy
  • Mitochondrial DNA Depletion
  • Mitochondrial Metabolism Disorders

Interventions

COMBINATION_PRODUCT

deoxycytidine and deoxythymidine

The Investigational Product (IP) dC/dT100-400 will be administered orally every day (QD) and the dose is divided over trid or bid for the daily dose of 100 mg/kg from Day 1-7, 200 mg/kg from Day 8-14, 300 mg/kg from Day 15- 21 and 400 mg/kg from Day 22 to 1825. Doses was chosen according to the safety and efficacy doses used in the literature.

Sponsors & Collaborators

  • Kenneth Myers, MD

    lead OTHER

Principal Investigators

  • Kenneth Alexis MD Myers, MD PhD FRCPC · RI-MUHC, Children Hospital of Montreal (MUHC), McGill University

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
1 Month
Max Age
60 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-10-18
Primary Completion
2029-06-30
Completion
2029-12-30

Countries

  • Canada

Study Locations

More Related Trials

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04802707 on ClinicalTrials.gov