A Phase 2 interventional study of mirtazapine in RETT Syndrome With Proven MECP2 Mutation, sponsored by University of Trieste. Recruiting at 4 sites in Italy. Open to female participants aged 5 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-02-24.
Sponsored by University of Trieste · Phase 2, Interventional, and Treatment
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.
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.
425 studies on the registry are indexed under Neurologic Manifestations; 82 are open to participants now.
This study's planned enrollment of 54 is above the median of 48 across 269 interventional studies indexed under Neurologic Manifestations.
Browse Neurologic Manifestations studies →University of Trieste is the lead sponsor of 39 studies on the registry; 8 are open to participants now.
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6. Ten episodes or more/day of breathing dysfunction during wakefulness in the week prior to the screening visit (parents report).
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).
EXCLUSION CRITERIA
Participants are excluded from the study if any of the following criteria apply:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Drug: mirtazapine
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).
Also known as: MirtaPil oral solution, Remeron oral solution
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.
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary endpoint 1. Reduced mood and anxiety disorder symptoms
1\. 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From enrollment to the end of treatment at 24 week
Secondary Endpoint 4. Regaining of hand control
4\. The drug will be considered effective if the Purposeful Hand Function scale (PHF) score increases at least 2 points above the pre-treatment score
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 5: Changes in Global severity
5\. 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.
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 6: Reduced Rett-specific Severity
6\. 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.
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 7: Improvement in respiratory parameters
7\. Drug efficacy will be determined by a reduction in the number of apnoeas-hypopnoeas by at least 5 events/hour.
Time frame: From enrollment to the end of treatment at 24 weeks
Secondary Endpoint 8: Decrease in caregivers burden
8\. 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From enrollment to the end of treatment at 24 weeks
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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".
Started Jul 2025 (actual). Primary completion is estimated for Jun 2026, 11 months after the start.
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Studies of the drug tested here: Mirtazapine
University of Trieste