Ignite Creation Date:
2024-05-06 @ 3:55 PM
Last Modification Date:
2024-10-26 @ 1:59 PM
Study NCT ID:
NCT04802707
Status:
RECRUITING
Last Update Posted:
2024-03-13
First Post:
2021-03-10
Brief Title:
Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
Sponsor:
McGill University Health CentreResearch Institute of the McGill University Health Centre
Organization:
McGill University Health CentreResearch Institute of the McGill University Health Centre
Study Overview
Official Title:
A Phase II Monocenter Single Arm Study To Assess The Safety and Efficacy Of Combination Deoxycytidine and Deoxythymidine For Mitochondrial Depletion Disorders
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
dC-dT-MDS
Brief 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 vitroin 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 C10orf2 RRM2B MPV17 SUCLA2 SUCLG1 FBXL4 Subjects with MDS expressing neurological phenotypes dysfunction
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 vitroin 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 C10orf2 RRM2B MPV17 SUCLA2 SUCLG1 FBXL4 Subjects with MDS expressing neurological phenotypes dysfunction
Detailed Description:
This Trial is designed as Phase II Monocenter Open label study in the pediatric population
The aim is to evaluate the safety tolerability and efficacy of Deoxycytidine and Deoxythymidine in treatment of children with Mitochondrial Depletion Disorders
Primary Objectives The primary objective of this study is to evaluate the efficacy of dCdT100-400 in subjects with mitochondria depletion disorders
Secondary Objectives The secondary objectives of this study are to evaluate tolerability and safety of dCdT100-400 in subjects with mitochondria depletion disorders
First Outcome
Efficacy of dCdT100-400
1 Neurological improvement by electroencephalography EEG seizure diary development and quality of life clinical status observed during the neurological follow-up
2 Improved clinical status observed during the genetic follow-up and the Newcastle Paediatric Mitochondrial Disease Scale NPMDS which are forms used by geneticist to allow evaluation of the progression of mitochondrial disease in patients less than 18 years of age
3 Bloodwork for different assessments
liver function aspartate aminotransferase AST alanine aminotransferase ALT gamma-glutamyl transferase GGT bilirubin and albumin kidney function creatinine urea electrolytes Assess for myopathy with serum creatine kinase CK Evaluation of mitochondrial function with capillaryvenous blood gas serum lactate plasma amino acids acylcarnitine profile urine amino acids urine purines and pyrimidines acids and growth differentiation factor 15 GDF15 a marker of severity of mitochondria dysfunction
Secondary Outcome
- Safety and tolerability will be tested by recording adverse effects AE AE will be monitored and collected throughout the study
1 Diarrhea Reported diarrhea frequency during the treatment will permit to define the tolerability of dCdT100-400
2 AE leading to study drug discontinuation treatment-emergent adverse events TEAEs SAEs Severe Adverse Effect will be reported from the first day the subjects start taking medication until the last dose taken
The aim is to evaluate the safety tolerability and efficacy of Deoxycytidine and Deoxythymidine in treatment of children with Mitochondrial Depletion Disorders
Primary Objectives The primary objective of this study is to evaluate the efficacy of dCdT100-400 in subjects with mitochondria depletion disorders
Secondary Objectives The secondary objectives of this study are to evaluate tolerability and safety of dCdT100-400 in subjects with mitochondria depletion disorders
First Outcome
Efficacy of dCdT100-400
1 Neurological improvement by electroencephalography EEG seizure diary development and quality of life clinical status observed during the neurological follow-up
2 Improved clinical status observed during the genetic follow-up and the Newcastle Paediatric Mitochondrial Disease Scale NPMDS which are forms used by geneticist to allow evaluation of the progression of mitochondrial disease in patients less than 18 years of age
3 Bloodwork for different assessments
liver function aspartate aminotransferase AST alanine aminotransferase ALT gamma-glutamyl transferase GGT bilirubin and albumin kidney function creatinine urea electrolytes Assess for myopathy with serum creatine kinase CK Evaluation of mitochondrial function with capillaryvenous blood gas serum lactate plasma amino acids acylcarnitine profile urine amino acids urine purines and pyrimidines acids and growth differentiation factor 15 GDF15 a marker of severity of mitochondria dysfunction
Secondary Outcome
- Safety and tolerability will be tested by recording adverse effects AE AE will be monitored and collected throughout the study
1 Diarrhea Reported diarrhea frequency during the treatment will permit to define the tolerability of dCdT100-400
2 AE leading to study drug discontinuation treatment-emergent adverse events TEAEs SAEs Severe Adverse Effect will be reported from the first day the subjects start taking medication until the last dose taken
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None