Lamivudine as a Novel Clinical Effort for Rett Syndrome

NCT07640503 | Enrolling By Invitation Phase 2 FDA Drug

• 1 other identifier: 88455225.8.0000.5534
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rett Syndrome

Keywords

Rett Syndrome; Lamivudine; Therapy

Outcome Measures

Primary Outcomes (3)

• Change in Rett Syndrome Symptom Severity (RARS)

  Change in Rett syndrome symptom severity assessed using the Rett Assessment Rating Scale (RARS), comparing total scores obtained at baseline with scores obtained after treatment with lamivudine and at post-treatment follow-up. Total scores range from 0 to 128, with higher scores indicating greater symptom severity. A reduction in total score will be interpreted as clinical improvement. Unit of Measure: Units on a scale (0-128)

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

• Change in Rett Syndrome Behavioral Symptoms

  Change in Rett syndrome behavioral symptoms assessed using the Rett Syndrome Behaviour Questionnaire (RSBQ), comparing total scores obtained at baseline with scores obtained at the end of treatment with lamivudine and at post-treatment follow-up. The RSBQ is a Rett syndrome-specific instrument used to assess behavioral, autonomic, and functional manifestations associated with Rett syndrome, including breathing abnormalities, irritability, anxiety, mood, repetitive hand movements, communication, and social interaction. The RSBQ consists of 45 items scored from 0 to 2, where 0 indicates "not true," 1 indicates "somewhat or sometimes true," and 2 indicates "often true" or "very true." Total scores range from 0 to 90, with higher scores indicating greater frequency or severity of behavioral symptoms and worse clinical status. A reduction in total score after treatment will be interpreted as improvement in Rett syndrome behavioral symptoms. Unit of Measure: Units on a scale (0-90)

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

• Safety of Lamivudine: Occurrence of Adverse Events

  Safety assessed by the number and proportion of participants experiencing at least one adverse event (serious or non-serious) during treatment with lamivudine, based on clinical assessment and laboratory monitoring. Unit of Measure: Number and proportion of participants with adverse events

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

Secondary Outcomes (32)

• Causality of Adverse Events (LCAT)

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

• Change in Health-Related Quality of Life: Pediatric Participants (PedsQL Neuromuscular Module)

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

• Change in Health-Related Quality of Life - Adult participants (SF-36)

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

• Change in Adaptive Behavior (Vineland Adaptive Behavior Scales - Adaptive Behavior Composite)

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

• Presence of Epileptic Seizures

  Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)

Study Arms (1)

Lamivudine Treatment

EXPERIMENTAL

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.

Drug: Lamivudine

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.

Lamivudine Treatment

Eligibility Criteria

• Age: 2 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical and molecular diagnosis of Rett syndrome;
• Age 2 years or older at the time of enrollment;
• Ability to swallow liquid medication;
• Stable clinical condition, as determined by the study investigator;
• Availability of a parent or legal guardian able to provide informed consent and comply with study procedures;
• Willingness of the participant and/or legal guardian to comply with study visits and assessments.

You may not qualify if:

• Known hypersensitivity or contraindication to lamivudine;
• Severe hepatic or renal impairment that, in the investigator's judgment, would preclude safe participation;
• Use of investigational drugs or participation in another clinical trial within a defined washout period before enrollment;
• Presence of any medical condition or acute illness that could interfere with study participation or outcome assessment, as determined by the investigator;
• Inability to undergo blood collection or skin biopsy procedures required for the study;
• Any condition that, in the opinion of the investigator, would place the participant at undue risk or compromise adherence to the study protocol.

Sponsors & Collaborators

• Maria Denise Fernandes Carvalho de Andrade: lead
• University of California, San Diego: collaborator

Study Sites (1)

GenClinics

Fortaleza, Ceará, Brazil

Location

Related Publications (1)

• Martins AMA, Nakashima H, Macia A, et al. Dormant viral pathways underlie space-induced neural senescence: a neuroprotective strategy for spaceflight and neurological diseases. bioRxiv. 2025. doi:10.1101/2025.11.02.686043

  BACKGROUND

Related Links

• Dormant viral pathways underlie space-induced neural senescence

MeSH Terms

Conditions

Rett Syndrome

Interventions

Lamivudine

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Maria Denise Fernandes Carvalho de Andrade, MD, PhD

  Universidade Estadual do Ceara

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Geneticist, and Physician

Model Details: This interventional study will be an open-label clinical trial with a duration of 24 weeks, designed to evaluate the safety and efficacy of repurposing lamivudine in patients with Rett syndrome. The study will follow the CONSORT 2010 (Consolidated Standards of Reporting Trials) guidelines to ensure transparency and integrity in the reporting of clinical trial results.

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: June 10, 2026
• Study Start: November 5, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)