RETT Syndrome With Proven MECP2 MutationPhase 2MirtaRettNCT07430046
Repurposing Mirtazapine in Rett Syndrome
A Phase 2 study testing mirtazapine in people with RETT Syndrome With Proven MECP2 Mutation, run by University of Trieste at 4 sites in Italy.
Trial summary
Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused by an MECP2 gene mutation on the X chromosome, primarily affecting females. It causes progressive motor and cognitive decline, loss of speech, repetitive hand movements, breathing issues, seizures, and sleep problems. Read more about this study
- Who is it for?
- Ages 5 to 40 years, women only
- Conditions the study is for
- RETT Syndrome With Proven MECP2 Mutation
- What is being tested?
- mirtazapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 4 sitesItaly
- Study dates
- 9 Jul 2025to 31 Dec 2026
- 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 5 to 40 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 1. Female aged 5 to 39 years inclusive, at the time of signing the informed consent.
- 2. Girls of childbearing age negative to pregnancy test;
- 3. Body weight > 10 kg. and within the expected range for RTT, based on age and height.
- 4. Diagnosis of RTT based on consensus clinical criteria (Neul, 2010) and a confirmed mutation in MECP2 gene.
- 5. Breathing dysfunction (at least one of the following): period apnoea, intermittent hyperventilation, breath holding spells, air swallowing, forced expulsion of air and /or saliva.
- 6. Ten episodes or more/day of breathing dysfunction during wakefulness in the week prior to the screening visit (parents report).
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- 7. Stable medication regimen for 4 weeks prior to beginning the study (if receiving services - physical, occupational, or speech therapy - subjects must be on a stable regimen of these services for 3 months prior to beginning the study).
- 8. Female patients of childbearing potential must use a highly effective contraceptive method such as combined hormonal contraception (containing estrogen and progestin) associated with ovulation suppression (oral, intravaginal, transdermal); progestin-only hormonal contraception associated with ovulation suppression (oral, injectable, implantable); intrauterine device; hormone-releasing intrauterine system. Sexual abstinence is considered a highly effective contraceptive method if it aligns with the individual's usual lifestyle. Female patients of childbearing potential are to use adequate contraception as recommended by their Health Care Provider.
- 9. Written consent signed by parent/legal guardian/representative prior to screening visit
- 10. Patient is cooperative, willing to complete the study, and capable of doing so with assistance of a caregiver.
- 11. Caregiver is able to understand the instructions and fully participate.
Who cannot join
- Participants are excluded from the study if any of the following criteria apply:
- Patient is participating to another investigational clinical trial.
- Hypersensitivity to MTZ or any of the other ingredients of Mirtapil®.
- Clinically significant (as determined by the investigator) cardiovascular, respiratory, gastrointestinal, renal, hepatic, haematological pathologies or other pathologies, in addition to those directly related to RTT. In particular, patients with the following parameters will be excluded: leucocyte count is < 4000/mm2; neutrophil count is < 2000/mm3; hyponatremia (< 125 mmol/L); renal dysfunction (creatinine > 2 X ULN), hepatic dysfunction (AST, ALT, bilirubin > 2 X ULN); or if severe diabetes mellitus is present.
- QTcF interval on the ECG greater than 450 msec
- Surgery planned during the study.
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- Severe diabetes mellitus (hyperglycaemia with values above 250/300 mg/dL);
- Pregnancy, breastfeeding.
- Evidence of clinically significant malnutrition with BMI (or BMI) (kg/m2) <
- Patients who manifested prior suicidal ideation.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy4 sites, 4 recruiting
- Recruiting
Unità di Neuropsichiatria Infantile, IRCCS, Istituto Giannina Gaslini, Genova
Genova, 16147
Lino Nobili, Prof, MD, 0039 010 5636 2432, neuropsichiatria@gaslini.org
Giulia Prato, MD, 0039 010 56363760, giuliaprato@gaslini.org
- Recruiting
UOC di Neuropsichiatria Infantile, Policlinico Universitario "Gaetano Martino" di Messina, University of Messina. Messina
Messina, 98125
Gabriella Di Rosa, Prof, MD, 0039 349 7386079, neuropsichiatria.infantile@polime.it
Antonio G Nicotera, MD, 0039 090 2212911, antoniogennaro.nicotera@polime.it
- Recruiting
Centro Epilessia - Unità Neurologia Pediatrica, ASST Ospedale Santi Carlo Paolo - Dipartimento Scienze della Salute, Università di Milano
Milan, 20142
Maria Paola Canevini, Prof. MD, 0039 02 8184.4201, epilessia.hsp@asst-santipaolocarlo.it
Ilaria Viganò, MD, ilaria.vigano@asst-santipaolocarlo.it
- Recruiting
Unità di Pediatria, Dipartimento della Donna e dei Bambini - Policlinico S. M. alle Scotte. Siena
Siena, 53100
Salvatore Grosso, Prof, MD, 0039 0577 586547, salvatore.grosso@ao-siena.toscana.it
Claudio De Felice, MD, 0039 347 330.9885, geniente@gmail.com
About this study
Official title: Repurposing Mirtazapine in Rett Syndrome: a Multicentric Open Label Phase II Study
Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused by an MECP2 gene mutation on the X chromosome, primarily affecting females. It causes progressive motor and cognitive decline, loss of speech, repetitive hand movements, breathing issues, seizures, and sleep problems. Given RTT's association with reduced monoamine levels, antidepressants like mirtazapine (MTZ) may help.Preclinical studies in MeCP2-mutant mice and early adult RTT trials showed that MTZ improved respiratory, motor, and neurological function, sleep, and mood, prompting this pediatric and young adult study. The MirtaRett trial is a multicenter, open-label, single-arm, phase II study enrolling 54 female RTT patients (ages 5-40), divided into groups of 18 (5-10, 11-17, 18-40 years). It aims to evaluate MTZ's safety and efficacy for mood, sleep, and motor symptoms, particularly hand control. Other ares of investigation include autonomic function, behavior, caregiver burden, clinical severity, and neuronal plasticity and metabolic biomarkers. Patients will receive escalating doses of MTZ oral solution: initial low doses (3.75-15 mg/day) for two weeks, followed by optimal doses (7.5-30 mg/day) for six months. Safety, tolerability, and symptoms will be monitored over 10 months (3-month screening, 6-month treatment, 1-month follow-up). The study is conducted at four Italian RTT-specialized hospitals, led by the University of Trieste. Partner sites are in Italy, specifically at the hospitals in Milan, Genova, Siena, and Messina.
Read the detailed description
Rett Syndrome (RTT) is a rare neurodevelopmental disease caused by a genetic mutation in the MECP2 gene located on the X chromosome and therefore particularly affects female subjects. It is characterised by an altered development of the nervous system leading to learning problems and delayed development of motor and cognitive skills. RTT is a progressive degenerative condition and there may be a worsening over time of the typical symptoms, including motor and cognitive impairments, loss of speech, repetitive hand movements, breathing abnormalities, gastrointestinal issues, mood disturbances, seizures and sleep problems. Given the reduced monoamine levels (serotonin, noradrenaline, dopamine) found in RTT, antidepressants -which modulates these neurotransmitters- may alleviate symptoms. Accordingly, mirtazapine (MTZ) was investigated, a noradrenergic and specific serotonergic antidepressant (NaSSA) for its potential benefits in RTT. Preclinical studies in MeCP2-mutant mice showed that MTZ improved respiratory, motor, and neurological function. In early human trials in RTT adults treated with MTZ for up to 5 years, reported benefits in sleep, mood, and social interactions, prompting this study in paediatric and young adult populations. Therefore, considering these preliminary results in humans, the hypothesis was put forward that MTZ could be beneficial also in RTT children.
MirtaRett is a multicenter, open-label, single-arm, phase II trial that will enroll 54 female RTT patients (ages 5-40), divided into three groups of 18 patients each (5-10 years, 11-17 years and 18-40 years). The overall goal of MirtaRett is to evaluate safety and efficacy of MTZ in the treatment of mood, sleep quality, motor symptoms in particular hand control, in Rett syndrome children and adults. Other areas that will be investigated include autonomic functions, behavior, caregiver burden and overall clinical severity along with neuroplasticity and metabolism biomarkers. Antidepressant drugs are typically administered using a scalar dosing approach, starting with low doses and gradually increasing them. Thus, patients will receive escalating doses of an oral solution of mirtazapine: initial low doses (3.75-15 mg/day) for two weeks, followed by optimal doses (7.5-30 mg/day) for six months. Safety, tolerability, and symptom changes will be monitored over 10 months (3-month screening, 6-month treatment, 1-month follow-up).
The study will be conducted across four Italian RTT-specialized hospitals, led by the University of Trieste.
- Coordinating centre - Department of Life Sciences, University of Trieste. Trieste, Italy.
- Partner 1. Epilepsy Center - Unit of Child Neurology, Hospital Santi Carlo Paolo and Department of Health Sciences, University of Milan, Milan, Italy.
- Partner 2. Unit of Child Neurology, Giannina Gaslini Institute, Genova, Italy.
- Partner 3. Pediatric Unit, Department of Woman and Child - Polyclinic Santa Maria alle Scotte. Siena, Italy.
- Partner 4. Department of Human Pathology in Adults and Children "Gaetano Barresi", University Polyclinic G. Martino, University of Messina. Messina, Italy.
- Conditions
- RETT Syndrome With Proven MECP2 Mutation
- Being tested
- mirtazapine
- Keywords
- antidepressant, mirtazapine, motor dysfunction, cognitive impairment, sleep disorder, cognitive disability, parent stress
- Medical subject headings
- Neurologic Manifestations, Cognitive Dysfunction, Sleep Wake Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mirtazapineDrug
Also called MirtaPil oral solution, Remeron oral solution
Study medication (3.75 mg, 7.5 mg, 15 mg, 30 mg of MTZ oral solution) will be given once daily at bedtime. During the first 14 days of the treatment period, the oral solution of the active drug at Dose Level 1 will be used to achieve the planned target daily dose, according to age (3.75 mg for 5-10 yrs, 7.5 mg for 11-17 yrs and 15 mg > 18 yrs, from day 1 to 14). From Day 15 to the end of week 24, Dose Level 2 will be achieved: 7.5 mg for 5-10 yrs, 15 mg for 11-17 yrs and 30 mg for > 18 yrs).
| Study group | Role | What they receive |
|---|---|---|
| Rett syndrome patients with MECP2 mutation and 5-40 years of age | Experimental | Subjects included in the study are female patients with a diagnosis of RTT, confirmed by mutation of the MECP2 gene, and who meet the inclusion/exclusion criteria of the study. The total number of participating patients is 54, aged between 5 and 40 years, divided into three groups of 18 patients each (5-10 years, 11-17 years and 18-40 years).
The study medication mirtazapine oral solution (MTZ) will be given once daily at bedtime. During the first 14 days of the treatment period, MTZ at Dose Level 1 will be used to achieve the planned target daily dose, according to age (3.75 mg for 5-10 yrs, 7.5 mg for 11-17 yrs and 15 mg >18 yrs, from day 1 to 14). From Day 15 to the end of week 24, Dose Level 2 will be achieved: 7.5 mg for 5-10 yrs, 15 mg for 11-17 yrs and 30 mg for > 18 yrs). Receives: Drug: mirtazapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Endpoint: Improvement in the rating scale Motor-Behavior Assessment Scale (MBAS).
The drug will be considered effective if the treatment decreases the Motor-Behavior Assessment Scale (MBAS) score (maximum score=68) by at least 8.5 points (12.5%) compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary outcomes (24)
Secondary endpoint 1. Reduced mood and anxiety disorder symptoms
- The drug will be considered effective if the treatment reduces the overall Anxiety, Depression, Mood Scale (ADAMS) score (maximum score=84) by at least 10.6 points (12.5%) compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 1bis: Reduced mood and anxiety disorder symptoms
1bis. The drug will be considered effective if is will reduce the overall Rett Syndrome Behaviour questionnaire (RSBQ) score by at least 11.25 points (12.5%) compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-a. Improved Vital parameters
2-a. The drug will be considered effective if the treatment improves the measurements of Respiratory Rate (RR), obtained from the medical devices for remote sensing (Youcare Smart T-shirt) by at least 20% compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-b. Improved Vital parameters
2-b. The drug will be considered effective if the treatment improves the measurements of Heart Rate (HR), obtained from the medical devices for remote sensing (Youcare Smart T-shirt) by at least 20% compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-c. Improved Vital parameters
2-c. The drug will be considered effective if the treatment improves the measurements of Variation of Heart Rate (VHR), obtained from the medical devices for remote sensing (Youcare Smart T-shirt) by at least 20% compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-d. Improved Vital parameters
2-d. The drug will be considered effective if the treatment improves the measurements of Skin Temperature (SkT) obtained from the medical devices for remote sensing (Youcare Smart T-shirt) by at least 20% compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 3-a: Improved Sleep quality
3-a. The drug will be considered efficacious if the Sleep Disturbances Scale for Children (SDSC) scores will be reduced by at least 20% compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 3-b: Improved Sleep Quality
3-b: The drug will be considered efficacious if the estimated time in bed (eTIB) measured by wrist actigraphy will be increasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 weeks.
Secondary Endpoint 3-c: Improved Sleep Quality
Description: 3-c: The drug will be considered efficacious if the estimated total sleep time (eTST), measured by wrist actigraphy, will be increasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-d: Improved Sleep Quality
Description: 3-d: The drug will be considered efficacious if the estimated sleep latency (eSOL), measured by wrist actigraphy, will be decreased by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-e: Improved Sleep Quality
Description: 3-e: The drug will be considered efficacious if the estimated sleep efficiency (eSE), measured by wrist actigraphy, will be increasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-f: Improved Sleep Quality
Description: 3-f: The drug will be considered efficacious if the estimated wake time after sleep onset (eWASO), measured by wrist actigraphy, will be decreasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-g: Improved Sleep Quality
Description: 3-g: The drug will be considered efficacious if the number of estimated awakenings (eAwk), measured by wrist actigraphy, will be decreasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-h: Improved Sleep Quality
Description: 3-h: The drug will be considered efficacious if the estimated sleep motor activity (eSMA), measured by wrist actigraphy, will be decreasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-i: Improved Sleep Quality
Description: 3-i: The drug will be considered efficacious if the num. ber of estimated naps (eNaps), num. ber of estimated naps (eNaps), will be decreasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-j: Improved Sleep Quality
Description: 3-j: The drug will be considered efficacious if the mean duration of the longest estimated nap (eNapD), measured by wrist actigraphy, will be increasing by 20% over the pre-treatment score.
Measured: From enrollment to the end of treatment at 24 week
Secondary Endpoint 4. Regaining of hand control
- The drug will be considered effective if the Purposeful Hand Function scale (PHF) score increases at least 2 points above the pre-treatment score
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 5: Changes in Global severity
- Drug efficacy will be determined using the Clinical Global Impression of Change (CGI-C) scale, which consists of a 7-point scale, ranging from 1 (very much improved) to 7 (very much worse), while 4 indicates no change. Decreased score of at least 1 point compared to the pre-treatment value is expected upon successful treatment.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 6: Reduced Rett-specific Severity
- Drug efficacy will be determined using the Rett Syndrome Severity Scale (RCSS), which consists of 13 items providing a rating of core symptoms of RTT on a Likert scale of either 0 to 4 or 0 to 5 with a maximum total score of 58. Drug will be considered efficacious if RCSS scores will result decreased by at least 3%, i.e. 2 points compared to the pre-treatment value.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 7: Improvement in respiratory parameters
- Drug efficacy will be determined by a reduction in the number of apnoeas-hypopnoeas by at least 5 events/hour.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 8: Decrease in caregivers burden
- The drug will be considered beneficial if the Parenting Stress Index (PSI-SF) specifically adjusted for Italian parents of Rett Syndrome girls, will show at least a 20% reduction of the pre-treatment Parenting Stress Index (PSI-SF).
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 9-a: Increased neurotrophic factors
9-a. Drug efficacy is targeted with 20% increase compared to the pre-treatment value of the serum levels of the biomarker BDNF measured in pg/ml.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 9-b: Increased neurotrophic factors
9-b. Drug efficacy is targeted with 20% increase compared to the pre-treatment value of the serum levels of the biomarker GDNF measured in pg/ml.
Measured: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 9-c: Increased neurotrophic factors
9-c. Drug efficacy is targeted with 20% increase compared to the pre-treatment value of the serum levels of the biomarker PDGF. measured in pg/ml.
Measured: From enrollment to the end of treatment at 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start9 Jul 2025
- Primary completion30 Jun 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RETT Syndrome With Proven MECP2 MutationStudies 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
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Trieste
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera Universitaria Policlinico "G. Martino", IRCSS Gianna Gaslini, Genova, Italy, Policlinico S.Maria alle Scotte, Siena, Italy, ASST Ospedale Santi Paolo e Carlo, Milano, Italy
- Responsible party
- Principal investigator, Enrico Tongiorgi, PhD, University of Trieste
- Investigators
- Enrico Tongiorgi, PhD, Principal investigator, University of Trieste, Trieste - Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07430046
- Sponsor's protocol ID
- CTIS ID: 28366
- Other IDs
- 2024-515411-21-00
- Acronym
- MirtaRett
- Status last verified
- Feb 2026
- First submitted
- 29 Jul 2025
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The Clinical Trial will be carried out in Italy only. Individual clinical data are therefore strictly protected by the Italian laws and regulations and cannot be shared in accordance withthe "Regolamento Generale sulla Protezione dei Dati (GDPR)" together with the "Codice Privacy" (Decreto Legislativo 196/2003), and its modifications under the "Decreto Legislativo 101/2018".
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing Mirtazapine in Rett Syndrome: a Multicentric Open Label Phase II Study
- ClinicalTrials.gov ID
- NCT07430046
- Acronym / sponsor ID
- MirtaRett / CTIS ID: 28366
- Conditions
- RETT Syndrome With Proven MECP2 Mutation
- Keywords
- antidepressant, mirtazapine, motor dysfunction, cognitive impairment, sleep disorder, cognitive disability, parent stress
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- University of TriesteUniversity, hospital or other
- Collaborators
- Azienda Ospedaliera Universitaria Policlinico "G. Martino", IRCSS Gianna Gaslini, Genova, Italy, Policlinico S.Maria alle Scotte, Siena, Italy, ASST Ospedale Santi Paolo e Carlo, Milano, Italy
- Study start
- 9 Jul 2025 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 24 Feb 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 neurodevelopmental disorder caused by an MECP2 gene mutation on the X chromosome, primarily affecting females. It causes progressive motor and cognitive decline, loss of speech, repetitive hand movements, breathing issues, seizures, and sleep problems. Given RTT's association with reduced monoamine levels, antidepressants like mirtazapine (MTZ) may help.Preclinical studies in MeCP2-mutant mice and early adult RTT trials showed that MTZ improved respiratory, motor, and neurological function, sleep, and mood, prompting this pediatric and young adult study. The MirtaRett trial is a multicenter, open-label, single-arm, phase II study enrolling 54 female RTT patients (ages 5-40), divided into groups of 18 (5-10, 11-17, 18-40 years). It aims to evaluate MTZ's safety and efficacy for mood, sleep, and motor symptoms, particularly hand control. Other ares of investigation include autonomic function, behavior, caregiver burden, clinical severity, and neuronal plasticity and metabolic biomarkers. Patients will receive escalating doses of MTZ oral solution: initial low doses (3.75-15 mg/day) for two weeks, followed by optimal doses (7.5-30 mg/day) for six months. Safety, tolerability, and symptoms will be monitored over 10 months (3-month screening, 6-month treatment, 1-month follow-up). The study is conducted at four Italian RTT-specialized hospitals, led by the University of Trieste. Partner sites are in Italy, specifically at the hospitals in Milan, Genova, Siena, and Messina.
Detailed description
Rett Syndrome (RTT) is a rare neurodevelopmental disease caused by a genetic mutation in the MECP2 gene located on the X chromosome and therefore particularly affects female subjects. It is characterised by an altered development of the nervous system leading to learning problems and delayed development of motor and cognitive skills. RTT is a progressive degenerative condition and there may be a worsening over time of the typical symptoms, including motor and cognitive impairments, loss of speech, repetitive hand movements, breathing abnormalities, gastrointestinal issues, mood disturbances, seizures and sleep problems. Given the reduced monoamine levels (serotonin, noradrenaline, dopamine) found in RTT, antidepressants -which modulates these neurotransmitters- may alleviate symptoms. Accordingly, mirtazapine (MTZ) was investigated, a noradrenergic and specific serotonergic antidepressant (NaSSA) for its potential benefits in RTT. Preclinical studies in MeCP2-mutant mice showed that MTZ improved respiratory, motor, and neurological function. In early human trials in RTT adults treated with MTZ for up to 5 years, reported benefits in sleep, mood, and social interactions, prompting this study in paediatric and young adult populations. Therefore, considering these preliminary results in humans, the hypothesis was put forward that MTZ could be beneficial also in RTT children.
MirtaRett is a multicenter, open-label, single-arm, phase II trial that will enroll 54 female RTT patients (ages 5-40), divided into three groups of 18 patients each (5-10 years, 11-17 years and 18-40 years). The overall goal of MirtaRett is to evaluate safety and efficacy of MTZ in the treatment of mood, sleep quality, motor symptoms in particular hand control, in Rett syndrome children and adults. Other areas that will be investigated include autonomic functions, behavior, caregiver burden and overall clinical severity along with neuroplasticity and metabolism biomarkers. Antidepressant drugs are typically administered using a scalar dosing approach, starting with low doses and gradually increasing them. Thus, patients will receive escalating doses of an oral solution of mirtazapine: initial low doses (3.75-15 mg/day) for two weeks, followed by optimal doses (7.5-30 mg/day) for six months. Safety, tolerability, and symptom changes will be monitored over 10 months (3-month screening, 6-month treatment, 1-month follow-up).
The study will be conducted across four Italian RTT-specialized hospitals, led by the University of Trieste.
- Coordinating centre - Department of Life Sciences, University of Trieste. Trieste, Italy.
- Partner 1. Epilepsy Center - Unit of Child Neurology, Hospital Santi Carlo Paolo and Department of Health Sciences, University of Milan, Milan, Italy.
- Partner 2. Unit of Child Neurology, Giannina Gaslini Institute, Genova, Italy.
- Partner 3. Pediatric Unit, Department of Woman and Child - Polyclinic Santa Maria alle Scotte. Siena, Italy.
- Partner 4. Department of Human Pathology in Adults and Children "Gaetano Barresi", University Polyclinic G. Martino, University of Messina. Messina, Italy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rett syndrome patients with MECP2 mutation and 5-40 years of age | Experimental | Drug: mirtazapineSubjects included in the study are female patients with a diagnosis of RTT, confirmed by mutation of the MECP2 gene, and who meet the inclusion/exclusion criteria of the study. The total number of participating patients is 54, aged between 5 and 40 years, divided into three groups of 18 patients each (5-10 years, 11-17 years and 18-40 years). The study medication mirtazapine oral solution (MTZ) will be given once daily at bedtime. During the first 14 days of the treatment period, MTZ at Dose Level 1 will be used to achieve the planned target daily dose, according to age (3.75 mg for 5-10 yrs, 7.5 mg for 11-17 yrs and 15 mg >18 yrs, from day 1 to 14). From Day 15 to the end of week 24, Dose Level 2 will be achieved: 7.5 mg for 5-10 yrs, 15 mg for 11-17 yrs and 30 mg for > 18 yrs). |
Who may qualify
- Ages
- 5 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 1. Female aged 5 to 39 years inclusive, at the time of signing the informed consent.
- 2. Girls of childbearing age negative to pregnancy test;
- 3. Body weight > 10 kg. and within the expected range for RTT, based on age and height.
- 4. Diagnosis of RTT based on consensus clinical criteria (Neul, 2010) and a confirmed mutation in MECP2 gene.
- 5. Breathing dysfunction (at least one of the following): period apnoea, intermittent hyperventilation, breath holding spells, air swallowing, forced expulsion of air and /or saliva.
Key exclusion criteria (10 listed)
- Patient is participating to another investigational clinical trial.
- Hypersensitivity to MTZ or any of the other ingredients of Mirtapil®.
- Clinically significant (as determined by the investigator) cardiovascular, respiratory, gastrointestinal, renal, hepatic, haematological pathologies or other pathologies, in addition to those directly related to RTT. In particular, patients with the following parameters will be excluded: leucocyte count is < 4000/mm2; neutrophil count is < 2000/mm3; hyponatremia (< 125 mmol/L); renal dysfunction (creatinine > 2 X ULN), hepatic dysfunction (AST, ALT, bilirubin > 2 X ULN); or if severe diabetes mellitus is present.
- QTcF interval on the ECG greater than 450 msec
- Surgery planned during 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 |
|---|---|---|
| mirtazapineAlso: MirtaPil oral solution, Remeron oral solutionStudy medication (3.75 mg, 7.5 mg, 15 mg, 30 mg of MTZ oral solution) will be given once daily at bedtime. During the first 14 days of the treatment period, the oral solution of the active drug at Dose Level 1 will be used to achieve the planned target daily dose, according to age (3.75 mg for 5-10 yrs, 7.5 mg for 11-17 yrs and 15 mg > 18 yrs, from day 1 to 14). From Day 15 to the end of week 24, Dose Level 2 will be achieved: 7.5 mg for 5-10 yrs, 15 mg for 11-17 yrs and 30 mg for > 18 yrs). | Drug | Rett syndrome patients with MECP2 mutation and 5-40 years of age |
Primary outcome
Primary Endpoint: Improvement in the rating scale Motor-Behavior Assessment Scale (MBAS).
Time frame: From enrollment to the end of treatment at 24 weeks
The drug will be considered effective if the treatment decreases the Motor-Behavior Assessment Scale (MBAS) score (maximum score=68) by at least 8.5 points (12.5%) compared to the pre-treatment value.
24 secondary outcomes
Secondary endpoint 1. Reduced mood and anxiety disorder symptoms
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 1bis: Reduced mood and anxiety disorder symptoms
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-a. Improved Vital parameters
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-b. Improved Vital parameters
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-c. Improved Vital parameters
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 2-d. Improved Vital parameters
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 3-a: Improved Sleep quality
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 3-b: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 weeks.
Secondary Endpoint 3-c: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-d: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-e: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-f: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-g: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-h: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-i: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 3-j: Improved Sleep Quality
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 4. Regaining of hand control
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 5: Changes in Global severity
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 6: Reduced Rett-specific Severity
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 7: Improvement in respiratory parameters
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 8: Decrease in caregivers burden
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 9-a: Increased neurotrophic factors
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 9-b: Increased neurotrophic factors
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 9-c: Increased neurotrophic factors
Time frame: From enrollment to the end of treatment at 24 weeks
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 24 Feb 2026.
- Individual participant dataSharing planned: No. The Clinical Trial will be carried out in Italy only. Individual clinical data are therefore strictly protected by the Italian laws and regulations and cannot be shared in accordance withthe "Regolamento Generale sulla Protezione dei Dati (GDPR)" together with the "Codice Privacy" (Decreto Legislativo 196/2003), and its modifications under the "Decreto Legislativo 101/2018".
Related trials for RETT Syndrome With Proven MECP2 Mutation
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GCB-002 in Treatment of Patients With Rett Syndrome
RETT Syndrome With Proven MECP2 Mutation
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Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
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Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders
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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.
Enrico Tongiorgi, PhD principal investigator
University of Trieste, Trieste - Italy
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mirtazapine in people with RETT Syndrome With Proven MECP2 Mutation, run by University of Trieste at 4 sites in Italy.
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 11 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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?
Contact Enrico Tongiorgi, PhD (+39 348 73477322, tongi@units.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Endpoint: Improvement in the rating scale Motor-Behavior Assessment Scale (MBAS). (time frame: From enrollment to the end of treatment at 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Feb 2026.