Lamivudine as a Novel Clinical Effort for Rett Syndrome

Sponsor
Maria Denise Fernandes Carvalho de Andrade
Study ID
NCT07640503
Phase
PHASE2
Status
Enrolling By Invitation

Conditions

Eligibility Criteria

Sex
FEMALE
Age
2 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Lamivudine — DRUG
    Lamivudine will be given orally to participants with Rett syndrome using weight-based dosing after baseline clinical and laboratory assessments. Children \<14 kg will receive oral solution at 4 mg/kg twice daily (max 300 mg/day). Participants ≥14 kg will receive tablets by weight: 14-20 kg, 150 mg/day; 20-25 kg, 225 mg/day; \>25 kg, 300 mg/day. Medication may be taken with or without food. Tablets should not be crushed unless swallowing is difficult. If needed, they may be crushed and mixed with liquid or soft food and taken immediately, or oral solution may be used. Caregivers will be instructed on dosing and concomitant medications. Treatment lasts 24 weeks with weekly safety, tolerability, and efficacy monitoring. Dose adjustment or discontinuation may occur if significant adverse events arise.

Study Details

Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder caused primarily by mutations in the MECP2 gene, leading to progressive impairments in motor function, communication, and behavior following an initial period of apparently typical development. Currently, there are no treatments that change the course of the disease, and clinical care is largely focused on managing symptoms. Loss of MeCP2 function has been associated with increased activity of the LINE-1 (L1) retroelement, which may contribute to neuroinflammation and cellular stress in the brain. Lamivudine, a nucleoside reverse transcriptase inhibitor widely used in antiviral therapy, can inhibit L1 reverse transcription and has shown beneficial effects in preclinical models of RTT, including reductions in inflammatory and oxidative stress markers and improvements in neurological and behavioral outcomes. This study aims to evaluate the safety and potential clinical and biological effects of lamivudine in individuals with Rett syndrome using a before-and-after treatment design. Participants will receive oral lamivudine and will undergo clinical assessments and laboratory testing before and after the treatment period to evaluate changes in symptom severity, functional status, quality of life, seizure activity, and biomarkers related to inflammation and neurodevelopment. Biological samples will also be collected to support translational laboratory studies aimed at improving understanding of disease mechanisms and treatment response in RTT. Results from this study may help determine whether lamivudine is a safe and promising therapeutic option and may guide future clinical research in this population.

Key Dates

Start date
Nov 5, 2025
Status verified
Jun 2026
Primary completion
Jun 30, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Lamivudine Treatment
    Approximately 10 participants aged ≥2 years with a confirmed clinical and molecular diagnosis of Rett syndrome will receive oral lamivudine using weight-based dosing for 24 weeks following baseline clinical and laboratory assessments. Participants will undergo regular monitoring for safety, tolerability, and efficacy, including clinical evaluations, laboratory testing, and assessment of neurological and functional outcomes. Dose adjustments or discontinuation may occur in response to adverse events. Blood samples will be collected for biomarker analyses, with an optional skin biopsy in a subset of participants for exploratory research.

Primary Outcome Measure

Change in Rett Syndrome Symptom Severity (RARS) [ Time Frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up) ]

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