Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome (RTI in AGS)
Aicardi Goutières Syndrome
About this trial
This is an interventional treatment trial for Aicardi Goutières Syndrome focused on measuring Leukodystrophy, Antiretroviral Drugs
Eligibility Criteria
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
Sites / Locations
- Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
TDF/FTC then Placebo
Placebo then TDF/FTC
This is a double-blind, placebo-controlled, 2 arm, cross-over trial involving 34 children with clinical findings and molecular confirmation of Aicardi Goutieres Syndrome, who also have an abnormal interferon signature. For arm 1, half of the patients will receive TDF/FTC (a combination of Tenofovir [TDF] and Emtricitabine [FTC]) for the first 6 months of the study. There will be a one month washout period before starting on placebo for 6 months.
For arm 2, half of the patients will receive placebo for the first 6 months of the study. There will be a one month washout period before starting on TDF/FTC (a combination of Tenofovir [TDF] and Emtricitabine [FTC]) for 6 months.