CompletedPhase 2

Inhibition of Reverse Transcription in Aicardi-Goutières Syndrome

United Kingdom13 participantsStarted 2022-08-24

Plain-language summary

Aicardi-Goutières syndrome (AGS) is a disease of children, particularly affecting the brain and the skin. There is a close link between AGS and increased amounts of a chemical called interferon. Normally humans only produce interferon when they are infected with a virus. In AGS, there is no viral infection. Instead, the cells in the cells of affected patients are confused into thinking that their own genetic material is coming from a virus. As a result they produce interferon all the time, which acts as a poison that damages the cells. The Investigators wish to treat AGS patients with drugs called reverse transcriptase inhibitors (RTIs), used to fight the HIV-1 virus that causes AIDS. The investigators will monitor the effect of treatment on interferon levels, and look at other markers which might give us clues to how the drugs are working. The trial is funded by the Medical Research Council, and involves experts based in Edinburgh, Birmingham, Manchester and Great Ormond Street Hospital.

Who can participate

Age range

3 Months – 15 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Patients with mutations in any of TREX1, the three components of the RNase H2 complex (RNASEH2A, RNASEH2B, RNASEH2C: considered as one genotype) or SAMHD1. * Greater than age 3 months and less than 16 years of age at the time of recruitment * Resident in the United Kingdom (UK) * Informed Consent obtained from parent or personal legal representative * For inclusion in the study, a patient has either to have completed the vaccination programme two weeks prior to starting the trial, or remain unvaccinated until the end of the trial, or agree to defer vaccination until immediately after a study drug arm, so that there is a period of at least two weeks following vaccination and before the start of the following drug arm. Exclusion Criteria: * Patients with AGS due to mutations in ADAR1 and IFIH1 will not be considered, given that the induction of interferon relating to these genotypes does not involve a reverse transcription step. * Pre-existing disease, not due to AGS, which would preclude the use of zidovudine, lamivudine and abacavir * Patients with abnormally low neutrophil counts (\<0.75 x 109/l) and / or abnormally low haemoglobin levels (\<7.5 g/dl)(particularly relevant to zidovudine), significant renal (creatinine clearance \< 50 ml/min; particularly relevant to lamivudine) or significant hepatic impairment (particularly relevant to abacavir; avoid if Child Pugh \> 5) * Participation in another Clinical Trial of an Investigational Medicinal Produ…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Determine if the use of the reverse transcriptase inhibitors abacavir (ABC), lamivudine (3TC) and zidovudine (AZT) reduces Interferon (IFN) signalling in patients with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C or SAMHD1

Timeframe: At 6 weeks

Trial details

NCT IDNCT04731103

SponsorUniversity of Edinburgh

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-03-11

View on ClinicalTrials.gov More Aicardi-Goutières Syndrome trials