Trial | NCT03304717  Report issue

Official Title

Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Status

    Not yet recruiting

  • Study Participants

    34
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.
The investigators propose that a trial to assess the proof of principle that antiretroviral therapy through a drug combination of Tenofovir (TDF) and Emtricitabine (FTC) can decrease endogenous retroelement accumulation, and alter interferon signaling in Aicardi Goutières Syndrome (AGS) patients is reasonable and warranted at this time, based on existing in vitro and animal data. Additionally, this trial will further the investigators understanding of this disorder, measuring for the first time retroelements in human participants, exploring the retroviral burden in cerebrospinal fluid (CSF), the Interferon (IFN) signaling response, as well as evaluating antigen targets of autoimmunity and cytokines. If successful, this approach will clearly demonstrate the need for a larger trial of antiretrovirals in AGS with more clinically relevant outcomes.
Study Started
Dec 31
2023
Anticipated
Primary Completion
Dec 31
2028
Anticipated
Study Completion
Dec 31
2028
Anticipated
Last Update
Jan 18
2023

Drug Tenofovir (TDF) and Emtricitabine (FTC) [tenofovir (viread), emtricitabine (emtriva)]

Tenofovir (TDF): a nucleotide reverse transcriptase inhibitor (NtRTI) an acyclic nucleotide analog of adenosine 5'-monophosphate. This is used in children as young as age 2. Emtricitabine (FTC): a nucleoside reverse transcriptase inhibitor (NRTI), a synthetic analog of cytidine which binds at the active site of the reverse transcriptase.

  • Other names: Truvada (Tenofovir Disoproxil Fumarate and Emtricitabine), Viread (Brand for tenofovir disoproxil fumarate), Emtriva (Brand for emtricitabine)

Other Placebo

Placebo for Tenofovir and Placebo for Emtricitabine

TDF/FTC then Placebo Experimental

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.

Placebo then TDF/FTC Experimental

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.

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
No Results Posted