ClinicalTrials.gov record NCT07430046

Repurposing Mirtazapine in Rett Syndrome

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

Repurposing Mirtazapine in Rett Syndrome: a Multicentric Open Label Phase II Study

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
Age5 years old to 40 years old
SexFemale
LocationItaly
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This is an open-label, single-arm Phase II trial testing the antidepressant mirtazapine (oral solution) in female patients with Rett syndrome and a confirmed MECP2 mutation. Fifty-four females aged 5–40 are divided into three age groups; treatment uses a 2-week low-dose escalation followed by a 6-month target-dose period, with safety and outcomes monitored over about 10 months total. The study measures mood, sleep, motor function (including hand control), autonomic signs, caregiver burden, clinical severity, and selected blood biomarkers.

What it is studying. The study is testing whether daily mirtazapine given at escalating then target doses is safe and how it affects mood, anxiety, sleep, breathing/autonomic measures, motor symptoms (notably purposeful hand use), overall clinical severity, caregiver stress, and selected neuroplasticity/metabolic biomarkers in people with Rett syndrome and a confirmed MECP2 mutation.

What the researchers hope to learn. To evaluate the safety profile of mirtazapine in Rett syndrome and to measure its effects on mood, sleep, motor control (including hand use), autonomic/respiratory parameters, caregiver burden, clinical severity, and selected neuroplasticity and metabolic biomarkers.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • mirtazapine

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Female aged 5 to 39 years inclusive, at the time of signing the informed consent.
  • Girls of childbearing age negative to pregnancy test;
  • Body weight > 10 kg. and within the expected range for RTT, based on age and height.
  • Diagnosis of RTT based on consensus clinical criteria (Neul, 2010) and a confirmed mutation in MECP2 gene.
  • Breathing dysfunction (at least one of the following): period apnoea, intermittent hyperventilation, breath holding spells, air swallowing, forced expulsion of air and /or saliva.
  • Ten episodes or more/day of breathing dysfunction during wakefulness in the week prior to the screening visit (parents report).
  • 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).
  • 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.
  • Written consent signed by parent/legal guardian/representative prior to screening visit
  • Patient is cooperative, willing to complete the study, and capable of doing so with assistance of a caregiver.
  • Caregiver is able to understand the instructions and fully participate.

Exclusion criteria

  • 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.
  • 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.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

After a screening period (up to 3 months), participants take mirtazapine oral solution once nightly for 24 weeks: a low dose for the first 14 days, then a target dose for the remainder, followed by a 1‑month follow-up. They will attend study visits for safety checks and symptom assessments, have blood tests (including biomarker measurements), ECGs and pregnancy tests as needed, and caregivers will complete questionnaires and rating scales. Participants will use wearable monitoring devices (Youcare Smart T‑shirt) and wrist actigraphy to record breathing and sleep/activity measures. Caregivers must be able to assist and participate throughout the study.

How the study is structured. Multicenter, open-label, single-group Phase II study: all participants receive nightly mirtazapine oral solution. Dosing starts low for two weeks, then continues at an age-based target dose for about six months. Assessments include clinical rating scales, wrist actigraphy for sleep, wearable vital-sign sensors, and blood biomarkers; there is no placebo or blinding.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in Italy. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Rett syndrome

Clinical trials20 trials listed for Rett syndromeEvery trial the registry lists for Rett syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Rett syndrome researchLatest monthly update: September 2026. Includes: Seizure add-on drug. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Jul 9, 2025
Primary completion
Jun 30, 2026 (estimated)
Study completion
Dec 31, 2026 (estimated)
Target enrollment
54 participants (estimated)
Last updated on registry
Feb 24, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
University of Trieste
Principal investigator
Enrico Tongiorgi, PhD, Full Professor
University of Trieste
Collaborators
  • Policlinico G . Martino, Messina Italy
  • IRCSS Gianna Gaslini, Genova, Italy
  • Policlinico S.Maria alle Scotte, Siena, Italy
  • ASST Ospedale Santi Paolo e Carlo, Milano, Italy

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (4)

Terms used on this page · explanations by MedicalUpdates.ai

open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
single-arm
All participants receive the same treatment or follow the same plan. There is no comparison group within the study.
biomarkers
Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
screening visit
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
stable regimen
A dose that has not changed for a defined period before the study starts. Studies may require this so that background treatment is relatively stable when study measurements begin.
childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
legal guardian
A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
neutrophil count
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
X ULN
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
QTcF
A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
INCLUSION CRITERIA
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
EXCLUSION CRITERIA
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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