Rett SyndromePhase 2LANCENCT07640503
Lamivudine as a Novel Clinical Effort for Rett Syndrome
A Phase 2 study testing Lamivudine in people with Rett Syndrome, run by Maria Denise Fernandes Carvalho de Andrade at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteBrazil
- Study dates
- 5 Nov 2025to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Lamivudine in Individuals With Rett Syndrome: Clinical, Biochemical, and Cellular Evaluation
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.
Read the detailed description
Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder caused primarily by loss-of-function mutations in the MECP2 gene, leading to progressive impairments in motor, cognitive, and communicative function after an initial period of apparently typical development. Currently, there are no medications that change the course of the disease, and treatment is mainly focused on managing symptoms.
Functional MeCP2 represses the activity of the LINE-1 (L1) retroelement, and loss of this repression may result in increased L1 accumulation in glial cells in the brain, promoting genomic instability, oxidative stress, and neuroinflammation associated with RTT pathophysiology.
Lamivudine inhibits L1 reverse transcription and has shown beneficial effects in preclinical neuronal culture and MeCP2-deficient mouse models, including reduced inflammatory and oxidative stress markers, improved neurological and behavioral outcomes, and increased survival. In this study, each participant is evaluated before and after receiving treatment, allowing changes to be assessed within the same individual over time. Following screening and baseline assessments, participants enter a treatment phase during which oral lamivudine is administered for a defined period. Longitudinal clinical, laboratory, and safety evaluations are conducted at scheduled visits, followed by a post-treatment follow-up period to assess the persistence of effects.
A 24-week intervention period was selected as a feasible and acceptable duration for participants and caregivers and as an appropriate timeframe for an initial open-label evaluation of therapeutic potential. This duration is expected to provide sufficient exposure to lamivudine to allow detection of short-term clinical and biological changes suggested by preclinical studies, while also enabling systematic assessment of safety and tolerability in this population.
Participants may continue their usual medical treatments, including medications for seizures and other supportive therapies, as long as these treatments remain stable during the study, unless a change is medically necessary.
Caregivers receive standardized instructions on medication administration, and adherence is monitored throughout the treatment phase through caregiver reporting and visit-based verification to ensure accurate assessment of treatment exposure.
Clinical assessments employ validated clinician and caregiver-reported instruments to evaluate symptom severity, functional status, quality of life, and seizure activity, capturing changes across motor, behavioral, and daily functioning domains relevant to RTT. Safety is monitored continuously through adverse event surveillance, routine clinical evaluations, and laboratory testing, with predefined criteria for treatment interruption if clinically indicated. Venous blood samples are collected at baseline and during treatment to evaluate systemic biomarkers related to oxidative stress, inflammation, and neurodevelopment. These measures complement clinical outcomes and explore potential mechanistic effects of lamivudine treatment.
In addition to the biomarkers reported as outcome measures, a panel of exploratory, hypothesis-generating biomarkers will be analyzed, including markers of oxidative stress, neuroinflammation and neurodevelopment, mitochondrial and energy metabolism, and nutritional and micronutrient status. These analyses are not considered clinical endpoints and are not reported as outcome measures.
As a translational research component, skin punch biopsies from a subset of participants are used to establish a dermal fibroblast biobank, enabling the generation of patient-derived induced pluripotent stem cells and brain organoids. These models will be used in exploratory laboratory studies to investigate cellular and molecular mechanisms in RTT and responses to lamivudine, without being considered clinical endpoints. Based on preclinical evidence and the proposed mechanism of action, lamivudine treatment is expected to be safe and well-tolerated in individuals with Rett syndrome. Clinically, it may lead to improvements in motor function, social engagement, and overall symptom severity, while reducing seizure frequency and enhancing quality of life. Biologically, lamivudine is anticipated to modulate oxidative stress and inflammatory pathways, potentially restoring a more balanced neurodevelopmental environment. The combined clinical and laboratory observations from this study will provide critical insights into the therapeutic potential of lamivudine and inform future research directions in RTT.
- Conditions
- Rett Syndrome
- Being tested
- Lamivudine
- Keywords
- Rett Syndrome, Lamivudine, Therapy
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamivudineDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Secondary outcomes (32)
Causality of Adverse Events (LCAT)
Causality of adverse events related to lamivudine assessed using the Liverpool Adverse Drug Reaction Causality Assessment Tool (LCAT). The tool classifies the causal relationship between the drug and each adverse event as unlikely, possible, probable, or definite. Higher categories indicate a greater likelihood of a causal relationship between the adverse event and lamivudine.
Unit of Measure: Number and proportion of adverse events in each causality category
Measured: 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)
Change in health-related quality of life assessed primarily by the PedsQL 3.0 Neuromuscular Module (PedsQL NMM), caregiver-report adapted version, comparing baseline scores with scores at the end of treatment and at follow-up. The PedsQL NMM yields transformed scores from 0 to 100; higher scores indicate better health-related quality of life and lower symptom impact. An increase after treatment is interpreted as improvement.
Unit of Measure: Units on a scale (0-100)
Measured: 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)
Change in health-related quality of life assessed by the Short Form (36) Health Survey (SF-36) in adult participants, comparing baseline scores with scores at the end of treatment and follow-up. SF-36 domain scores range from 0 to 100, with higher scores indicating better quality of life. An increase in score after treatment is interpreted as improvement.
Unit of Measure: Units on a scale (0-100)
Measured: 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)
Change in adaptive behavior assessed using the Vineland Adaptive Behavior Scales, reported as the Adaptive Behavior Composite standard score, comparing baseline with end-of-treatment and follow-up values. Standard scores have a mean of 100 and a standard deviation of 15, higher scores indicate better adaptive functioning.
Unit of Measure: Standard score
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Presence of Epileptic Seizures
Presence of epileptic seizures during treatment with lamivudine, assessed by the number of participants experiencing at least one epileptic seizure after the start of the intervention. Data obtained from caregiver records and clinical assessment by the research team.
Unit of Measure: Participants
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Frequency of Epileptic Seizures
Change in the frequency of epileptic seizures, comparing the mean number of seizures per participant at baseline with the mean number recorded during treatment with lamivudine. Information obtained from a caregiver-completed seizure diary, confirmed at follow-up visits.
Unit of Measure: Number of seizures per month
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Need for Medical Intervention Related to Epileptic Seizures
Need for medical intervention related to epileptic seizures during treatment with lamivudine, assessed by the number of participants requiring emergency care, hospitalization, or rescue medication due to an epileptic seizure.
Unit of Measure: Participants
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Caregiver Burden (Zarit Burden Interview, ZBI-22)
Change in caregiver burden assessed using the Zarit Burden Interview (ZBI-22), comparing baseline scores with scores at the end of treatment and at follow-up. Total scores range from 0 to 88, with higher scores indicating greater caregiver burden. A reduction in total score after treatment is interpreted as improvement.
Unit of Measure: Units on a scale (0-88)
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Global Clinical Severity (CGI-S)
Change in global clinical severity assessed by the Clinical Global Impression Severity (CGI-S) scale, comparing the score at baseline with the score at the end of treatment. The CGI-S is a 7-point clinician-rated scale ranging from 1 to 7, where 1 = normal (not at all ill) and 7 = among the most extremely ill patients. Higher scores indicate greater global clinical severity. A reduction after treatment is interpreted as clinical improvement.
Unit of Measure: Units on a scale (1-7)
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Global Clinical Improvement (CGI-I)
Global clinical improvement assessed using the Clinical Global Impression-Improvement scale (CGI-I) at the end of lamivudine treatment and during post-treatment follow-up. Scores range from 1 ("very much improved") to 7 ("very much worse"), with lower scores indicating greater improvement.
Unit of Measure: Units on a scale (1-7)
Measured: Week 24 and Week 52
Change in serum C-reactive protein (CRP)
Change in serum C-reactive protein (CRP) concentrations, comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/L
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Monocyte chemoattractant protein-1 (MCP-1)
Change in serum Monocyte chemoattractant protein-1 (MCP-1), comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: pg/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Ferritin
Change in serum Ferritin, comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: ng/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-1 beta (IL-1β)
Change in serum Interleukin-1 beta (IL-1β), comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: pg/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-6 (IL-6)
Change in serum Interleukin-6 (IL-6), comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: pg/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-8 (IL-8)
Change in serum Interleukin-8 (IL-8), comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: pg/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-10 (IL-10)
Change in serum Interleukin-10 (IL-10), comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: pg/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Tumor Necrosis Factor alpha (TNF-α)
Change in serum Tumor Necrosis Factor alpha (TNF-α), comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: pg/mL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Aspartate aminotransferase (AST/TGO)
Change in serum Aspartate aminotransferase (AST/TGO) levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: U/L
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Alanine aminotransferase (ALT/TGP)
Change in serum Alanine aminotransferase (ALT/TGP) levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: U/L
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Alkaline phosphatase
Change in serum Alkaline phosphatase levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: U/L
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Urea
Change in serum Urea levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Creatinine
Change in serum Creatinine levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Glucose
Change in serum Glucose levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Uric acid
Change in serum Uric acid levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Total bilirubin
Change in serum total bilirubin levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Direct bilirubin
Change in serum direct bilirubin levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: mg/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Albumin
Change in serum albumin levels comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: g/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Hemoglobin
Change in hemoglobin comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: g/dL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Hematocrit
Change in hematocrit comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: %
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Leukocyte count
Change in leukocyte count comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: cells/µL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Platelet count
Change in platelet count comparing values at baseline with values at the end of treatment and at follow-up.
Unit of Measure: cells/µL
Measured: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2026
- Study start5 Nov 2025
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maria Denise Fernandes Carvalho de Andrade
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Diego
- Responsible party
- Sponsor-investigator, Maria Denise Fernandes Carvalho de Andrade, Universidade Estadual do Ceara
- Investigators
- Maria Denise Fernandes Carvalho de Andrade, MD, PhD, Principal investigator, Universidade Estadual do Ceara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07640503
- Sponsor's protocol ID
- 88455225.8.0000.5534
- Acronym
- LANCE
- Status last verified
- Jun 2026
- First submitted
- 12 May 2026
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lamivudine in Individuals With Rett Syndrome: Clinical, Biochemical, and Cellular Evaluation
- ClinicalTrials.gov ID
- NCT07640503
- Acronym / sponsor ID
- LANCE / 88455225.8.0000.5534
- Conditions
- Rett Syndrome
- Keywords
- Rett Syndrome, Lamivudine, Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Maria Denise Fernandes Carvalho de AndradeUniversity, hospital or other
- Collaborators
- University of California, San Diego
- Study start
- 5 Nov 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder caused primarily by loss-of-function mutations in the MECP2 gene, leading to progressive impairments in motor, cognitive, and communicative function after an initial period of apparently typical development. Currently, there are no medications that change the course of the disease, and treatment is mainly focused on managing symptoms.
Functional MeCP2 represses the activity of the LINE-1 (L1) retroelement, and loss of this repression may result in increased L1 accumulation in glial cells in the brain, promoting genomic instability, oxidative stress, and neuroinflammation associated with RTT pathophysiology.
Lamivudine inhibits L1 reverse transcription and has shown beneficial effects in preclinical neuronal culture and MeCP2-deficient mouse models, including reduced inflammatory and oxidative stress markers, improved neurological and behavioral outcomes, and increased survival. In this study, each participant is evaluated before and after receiving treatment, allowing changes to be assessed within the same individual over time. Following screening and baseline assessments, participants enter a treatment phase during which oral lamivudine is administered for a defined period. Longitudinal clinical, laboratory, and safety evaluations are conducted at scheduled visits, followed by a post-treatment follow-up period to assess the persistence of effects.
A 24-week intervention period was selected as a feasible and acceptable duration for participants and caregivers and as an appropriate timeframe for an initial open-label evaluation of therapeutic potential. This duration is expected to provide sufficient exposure to lamivudine to allow detection of short-term clinical and biological changes suggested by preclinical studies, while also enabling systematic assessment of safety and tolerability in this population.
Participants may continue their usual medical treatments, including medications for seizures and other supportive therapies, as long as these treatments remain stable during the study, unless a change is medically necessary.
Caregivers receive standardized instructions on medication administration, and adherence is monitored throughout the treatment phase through caregiver reporting and visit-based verification to ensure accurate assessment of treatment exposure.
Clinical assessments employ validated clinician and caregiver-reported instruments to evaluate symptom severity, functional status, quality of life, and seizure activity, capturing changes across motor, behavioral, and daily functioning domains relevant to RTT. Safety is monitored continuously through adverse event surveillance, routine clinical evaluations, and laboratory testing, with predefined criteria for treatment interruption if clinically indicated. Venous blood samples are collected at baseline and during treatment to evaluate systemic biomarkers related to oxidative stress, inflammation, and neurodevelopment. These measures complement clinical outcomes and explore potential mechanistic effects of lamivudine treatment.
In addition to the biomarkers reported as outcome measures, a panel of exploratory, hypothesis-generating biomarkers will be analyzed, including markers of oxidative stress, neuroinflammation and neurodevelopment, mitochondrial and energy metabolism, and nutritional and micronutrient status. These analyses are not considered clinical endpoints and are not reported as outcome measures.
As a translational research component, skin punch biopsies from a subset of participants are used to establish a dermal fibroblast biobank, enabling the generation of patient-derived induced pluripotent stem cells and brain organoids. These models will be used in exploratory laboratory studies to investigate cellular and molecular mechanisms in RTT and responses to lamivudine, without being considered clinical endpoints. Based on preclinical evidence and the proposed mechanism of action, lamivudine treatment is expected to be safe and well-tolerated in individuals with Rett syndrome. Clinically, it may lead to improvements in motor function, social engagement, and overall symptom severity, while reducing seizure frequency and enhancing quality of life. Biologically, lamivudine is anticipated to modulate oxidative stress and inflammatory pathways, potentially restoring a more balanced neurodevelopmental environment. The combined clinical and laboratory observations from this study will provide critical insights into the therapeutic potential of lamivudine and inform future research directions in RTT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Lamivudine Treatment | Experimental | Drug: LamivudineApproximately 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LamivudineLamivudine 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. | Drug | Lamivudine Treatment |
Primary outcome
Change in Rett Syndrome Symptom Severity (RARS)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
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)
Change in Rett Syndrome Behavioral Symptoms
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
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)
Safety of Lamivudine: Occurrence of Adverse Events
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
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
32 secondary outcomes
Causality of Adverse Events (LCAT)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Presence of Epileptic Seizures
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Frequency of Epileptic Seizures
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Need for Medical Intervention Related to Epileptic Seizures
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Caregiver Burden (Zarit Burden Interview, ZBI-22)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Global Clinical Severity (CGI-S)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Global Clinical Improvement (CGI-I)
Time frame: Week 24 and Week 52
Change in serum C-reactive protein (CRP)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Monocyte chemoattractant protein-1 (MCP-1)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Ferritin
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-1 beta (IL-1β)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-6 (IL-6)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-8 (IL-8)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Interleukin-10 (IL-10)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Tumor Necrosis Factor alpha (TNF-α)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Aspartate aminotransferase (AST/TGO)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Alanine aminotransferase (ALT/TGP)
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Alkaline phosphatase
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Urea
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Creatinine
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Glucose
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Uric acid
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Total bilirubin
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Direct bilirubin
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in serum Albumin
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Hemoglobin
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Hematocrit
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Leukocyte count
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Change in Platelet count
Time frame: Baseline (Week 0), Week 24 (end of treatment), and Week 52 (post-treatment follow-up)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- BackgroundMartins 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
- Dormant viral pathways underlie space-induced neural senescenceLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Rett Syndrome
RecruitingPhase 3
A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome
Rett Syndrome
Active, not recruiting
Measuring Impact of Computer Gaming on Arm Use in Rett Syndrome
Rett Syndrome
Active, not recruiting
Technology-supported Motor Rehabilitation for People With Rett Syndrome
Rett Syndrome
RecruitingObservational study
Neurophysiologic Biomarkers in Rett Syndrome
Rett Syndrome, RTT
RecruitingPhase 1/2
ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)
Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Maria Denise Fernandes Carvalho de Andrade, MD, PhD principal investigator
Universidade Estadual do Ceara
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lamivudine in people with Rett Syndrome, run by Maria Denise Fernandes Carvalho de Andrade at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07640503, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.