Aicardi Goutières Syndrome Clinical Trial
— RTI in AGSOfficial title:
Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome
The overall objectives are to explore the safety and efficacy of Reverse Transcriptase Inhibitors Tenofovir (TDF)/ Emtricitabine (FTC) administered in AGS affected children 2 to 18 years of age.
| Status | Not yet recruiting |
| Enrollment | 34 |
| Est. completion date | December 2028 |
| Est. primary completion date | December 2028 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 18 Years |
| Eligibility | Inclusion Criteria: - Molecular, neuroimaging, and clinical findings consistent with a diagnosis of AGS, with the exception of Double-stranded RNA-specific adenosine deaminase (ADAR1) and IFIH1, which are not postulated to result in nucleic acid accumulation - Evidence of interferon activation such as elevation of CSF neopterin/tetrahydrobiopterin measured on the first evaluation. - Ages 2-18 years (the age of 2 years is used because the drugs are FDA approved in children greater than 2 years) - Weight of at least 10 kg - Willingness to undergo serial lumbar punctures and blow draws for evaluation of laboratory based outcome measures - Willingness to abstain from initiating the use of immune modulating therapies including corticosteroids - Able to receive medications orally, by nasogastric (NG) tube or by Gastric (G)-tube - No concomitant illness which would preclude safe participation as judged by the investigator - Signed informed consent by the subject's legally acceptable representative - Negative testing for HIV - Negative testing for Hepatitis B - Concurrent enrollment in the Myelin Disorders Biorepository Project (MDBP, ClinicalTrials.gov NCT03047369) and willingness to undergo associated procedures Exclusion Criteria: - Age < 2 years or >18 years - Hepatic insufficiency with liver function tests greater than 3-times the upper limit of normal - Renal insufficiency with creatinine clearance <60 - Significant malabsorption - Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at an additional risk by participating in this study - HIV infection - Hepatitis B infection - Mutations in ADAR1 or IFIH1 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Children's Hospital of Philadelphia | Emerson Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Gilead Sciences, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in interferon activation as measured by interferon response genes | The investigators propose to measure genes in the IFN stimulatory pathway in AGS patients, as a measure of disease activity and as a possible biomarker of therapeutic activity. Current data suggests that IFN related genes remain elevated in the late teens in AGS affected subjects, making it a more reliable measure of disease activity than IFN alpha. Validation of this preliminary data includes serial measurements in blood across several time points, to assess for variability. | From Baseline to 13 months | |
| Secondary | Determination of immune cell composition in CSF | The investigators will pursue immunophenotyping of CSF cells in AGS subjects. Immunophenotyping and target antigens will further understanding of end organ damage in AGS. Additionally, this may provide biomarkers for therapeutic outcome and disease activity. | From Baseline to 13 months | |
| Secondary | Determination of immune cell composition in blood | The investigators will pursue immunophenotyping of peripheral blood monocytes in AGS participants. Immunophenotyping and target antigens will further our understanding of end organ damage in AGS. Additionally, this may provide biomarkers for therapeutic outcome and disease activity. | From Baseline to 13 months | |
| Secondary | Accumulation of endogenous retroelements as measured in circulating immune cells | Performed by assays from previously collected samples | From Baseline to 13 months | |
| Secondary | Accumulation of endogenous retroelements as measured in circulating CSF | Performed by assays from previously collected samples | From Baseline to 13 months | |
| Secondary | Change in presence of non-specific and specific autoantibodies in blood | Performed by assays from previously collected samples | From Baseline to 13 months | |
| Secondary | Changes in Adverse Events - Safety monitoring laboratory tests | Patient monitoring for adverse effects | From Baseline to 13 months and as clinically warranted | |
| Secondary | Changes in total days hospitalized for disease-related illnesses. | Assess the effects of the treatment | Baseline - 13 months |